ORIGINAL STUDY
Improving Standard of Care Through Introduction of Laparoscopy for the Surgical Management of Gynecological Malignancies Giorgio Bogani, MD,* Antonella Cromi, PhD,* Maurizio Serati, MD,* Edoardo Di Naro, MD,Þ Jvan Casarin, MD,* Ciro Pinelli, MD,* Ilario Candeloro, MD,* Davide Sturla, MD,* and Fabio Ghezzi, MD*
Objective: This study aimed to evaluate the impact on perioperative and medium-term oncologic outcomes of the implementation of laparoscopy into a preexisting oncologic setting. Methods: Data from consecutive 736 patients undergoing surgery for apparent early stage gynecological malignancies (endometrial, cervical, and adnexal cancers) between 2000 and 2011 were reviewed. Complications were graded per the Accordion classification. Survival outcomes within the first 5 years were analyzed using Kaplan-Meier method. Results: Overall, 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery via laparoscopy through the years (from 10% in the years 20002003 to 82% in years 2008-2011; P G 0.001 for trend); while the need to perform open surgery decreased dramatically (from 83% to 10%; P G 0.001). Vaginal approach was nearly stable over the years (from 7% to 8%; P = 0.76). A marked reduction in estimated blood loss, length of hospital stay, blood transfusions as well as grade greater than or equal to 3 postoperative complications over the years was observed (P G 0.001). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P 9 0.05). The introduction of laparoscopy did not adversely affect medium-term (within 5 years) survival outcomes of patients undergoing surgery for apparent early stage cancers of the endometrium, uterine cervix, and adnexa (P 9 0.05 log-rank test). Conclusions: The introduction of laparoscopy into a preexisting oncologic service allows an improvement of standard of care due to a gain in perioperative results, without detriments of medium-term oncologic outcomes. Key Words: Laparoscopy, Endometrial cancer, Cervical cancer, Ovarian cancer, Survival Received April 20, 2014, and in revised form January 4, 2015. Accepted for publication January 4, 2015. (Int J Gynecol Cancer 2015;25: 741Y750)
represents the mainstay of treatment for women S urgery affected by gynecological malignancies. During the past
2 decades, technical and technological innovations have
brought a new frontier in cancer treatments.1Y3 In particular, the introduction of laparoscopic surgery has profoundly changed the approach to cancers’ treatments. Historically,
*Department of Obstetrics and Gynecology, University of Insubria, Varese; and †Department of Obstetrics and Gynecology, University of Bari, Bari, Italy. Copyright * 2015 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1097/IGC.0000000000000406
Address correspondence and reprint requests to Giorgio Bogani, MD, Department of Obstetrics and Gynecology, University of Insubria, Piazza Biroldi, 1, Varese 21100, Italy. E-mail: [email protected]. The authors declare no conflicts of interest.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
741
Bogani et al
International Journal of Gynecological Cancer
curative cancer surgery was ‘‘macrosurgery,’’ for which long abdominal incision and intra-abdominal organ manipulations were mandatory requirements.4 Then, in recent years, surgical oncology practice has evolved gradually; minimally invasive surgery continues to emerge in each surgical field and evolve as new technology develops.3,5 Albeit high levels of evidence support the use of laparoscopic approach (at least for the treatment of endometrial cancer), the embrace of laparoscopy in the treatment of gynecological malignancies seems to evolve slower than as expected.6 In fact, although several studies have shown that laparoscopy overcomes open surgery for both short-term7Y14 and long-term outcomes,15 what really the introduction of laparoscopy has changed into the clinical practice is far from clear. In fact, only limited data showing the degree of the shift from open abdominal to minimally invasive surgery into the clinical practice are available.7,16Y19 Hence, it is difficult to estimate what really happened in the setting of routine workload rather than the context of clinical trials. In 2009, we reported how the introduction of laparoscopy has influenced our practice.7 Five years later, we sought to analyze how the implementation of laparoscopic surgery has modified our routine practice. We aimed to describe our experience, reporting perioperative as well as long-term outcomes of consecutive patients undergoing surgical treatment for gynecological malignancies, thus allowing analyzing the impact of laparoscopy in a concrete clinical setting.
MATERIALS AND METHODS We retrospectively reviewed data of consecutive patients undergoing surgical treatment for early stage cancer of the endometrium, uterine cervix, and adnexa between January 1, 2000, and December 31, 2011, at the Department of Gynecology of University of Insubria (department A) and the Department of Obstetrics and Gynecology-Ospedale di Circolo Fondazione Macchi (department B). Both the departments are located in the same hospital in Varese (Italy) and they become a single Gynecologic Oncology Unit since 2010. In our institutions, research activities involving the study of existing data are exempt from the requirement for institutional review board approval. For the purpose of this study, patients affected by tumors (ie, molar disease, vulvar cancer) for which the use of open abdominal/laparoscopic surgery is generally not applicable were excluded.7 Patients were allocated in 3 groups according their malignancy (endometrial, cervical, and adnexal cancers). Low malignant potential ovarian tumors were not included, because their presence could impair the analysis, improving surgical and survival outcomes. In case of synchronous tumors, patients were allocated in the group considered at higher risk (ie, patients with synchronous adnexal and uterine cancer were allocated in the adnexal cancer group). Early stage of disease was defined as organ-confined cancer, with the absence of macroscopic gross intra-abdominal disease. In 2002, 2003, and 2004, we started a policy of systematic implementation of laparoscopic staging for uterine corpus, malignant ovarian, and cervical cancers, respectively.7 Detailed descriptions of surgical technique are reported elsewhere.3,7,20Y23 Laparoscopic devices (including trocars,
742
& Volume 25, Number 4, May 2015
laparoscopic instruments, and uterine manipulator (RUMIKoh) were for mostly reusable.3 Usually, disposable vessels sealing devices were not used. After the implementation of minimal access surgery, laparoscopic approach was attempted in all women who presented to our institution, unless specific contraindications to laparoscopic surgery existed, such as documented severe cardiopulmonary disease. No patient was refused laparoscopy for reasons of uterus size, age, obesity, prior surgical history, or anticipated difficulty of resection. Active attempts were used to decrease the risk of intra-abdominal spillage and loss of surgical debris.7,22 The same team of surgeons, who were assisted by residents and trainees, performed all surgical procedures. Data concerning the surgical procedures, postoperative details, adjuvant therapy as well as follow-up evaluations were recorded prospectively in our computerized oncologic database, a research-quality database maintained by trained residents and updated on a regular basis. Data including age, body mass index, and medical/surgical history were abstracted retrospectively. Comorbidity levels were assessed using the Charlson comorbidity index.21 To evaluate changes in the management of cancer patients, 3 study periods were analyzed: T1 (2000-2003), in which laparoscopic surgery was first introduced but open surgery represented the standard of care; T2 (2004-2007), in which we assisted at a systematic implementation of laparoscopic surgery; and T3 (2008-2011), in which laparoscopic surgery was the standard of care. During the study period, there were no significant differences in patients’ care for each surgical technique. Interventions were performed under general endotracheal anesthesia. Operative times were recorded from the first skin incision to the last suture (skin to skin). Blood loss was estimated from the contents of suction devices. Hospital stay was counted from the first postoperative day. Organ damage, blood transfusion, and the need to conversion to laparotomy (for women who had laparoscopic surgery) were considered as intraoperative complications. Postoperative complications were graded per the Accordion Severity System.24 For the purpose of this study, only grade greater than or equal to 3 complications, occurred within the first 8 weeks after surgery, were reported. Martin criteria were applied to improve quality in complications reporting.25 Readmissions (for more than 24 hours) that occurred within 8 weeks were reported. Adjuvant therapy (radiotherapy and/or chemotherapy) was delivered according to diseases and clinical protocols.7 Follow-up evaluations, with pelvic examination and ultrasound examination, were planned according to institutional protocols.3,7,13 Dates and sites of recurrence were recorded. Recurrences were classified in local (vaginal), regional (lymphatic), and distant. Patients were considered by intention to treat principle. Hence, for statistical purpose, patients who had conversion from laparoscopy or vaginal to surgery to open were considered in the laparoscopic and vaginal group, respectively. Statistical analysis was performed with GraphPad Prism version 6.0 for Mac (GraphPad Software, San Diego, CA). Normality testing (D’Agostino and Pearson test) was performed to determine whether data were sampled from a Gaussian distribution. * 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
One-way analysis of variance and Kruskal-Wallis test were performed to compare 3 or more groups of continuous parametric and nonparametric variables, respectively. The W2 test was used to analyze proportions. Incidence of events between 2 groups was analyzed for statistical significance by using the Fisher exact test. Odds ratio and 95% confidence intervals were calculated for each comparison. When we evaluated only 2 groups, t test and Mann-Whitney U test were used to compare continuous parametric and nonparametric variables, respectively. Disease-free and overall survivals within 5 years were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Trends over the times for continuous variables and proportions were assessed using
Laparoscopy for Gynecological Cancers
posttest for linear trend and W2, respectively. P values less than 0.05 were considered statistically significant.
RESULTS Overall, 736 patients undergoing surgical treatment for gynecological malignancies between January 1, 2000, and December 31, 2011, were available for the analysis: 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery through the years (from 204 in T1 to 300 in T3; +50%); whereas the percentages of endometrial, cervical, and adnexal cancers were stable over the whole study period (P 9 0.05).
TABLE 1. Changes in gynecological malignancies management P
T1 (2000-2003), n = 204 T2 (2004-2007), n = 232 T3 (2008-2011), n = 300 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Gynecological cancer Endometrium Uterine cervix Adnexa Approach Open abdominal Laparoscopic Vaginal Conversion LND (PL T PA LND) Lymph node count Operative time, min Estimated blood loss, mL Hospital stay, d Transfusion Intraoperative complications Postoperative complication‡‡ Adjuvant therapy
61 27 106 6
(27Y93) (18.8Y68) (52%) (3%)
64 26.8 106 14
(13Y90) (17.4Y46) (46%) (6%)
62 26.2 131 36
(20Y92) (15.8Y50.8) (44%) (12%)
145 (71%) 45 (22%) 14 (7%)
153 (66%) 53 (23%) 26 (11%)
195 (65%) 64 (21%) 41 (14%)
169 (83%) 21 (10%) 14 (7%) 0 (0%) 126 (62%) 20 (3Y60) 150 (25Y930) 200 (10Y2000) 6 (1Y34) 29 (14%) 5 (2%) 23 (11%) 56 (27%)
85 (36%) 140 (60%) 7 (3%) 4 (2%) 177 (76%) 19 (5Y58) 185 (30Y480) 150 (10Y3000) 4 (1Y30) 20 (9%) 7 (3%) 9 (4%) 94 (41%)
31 248 21 5|| 212 20 135 150 2 14 3 3 113
(10%) (82%) (8%) (2%) (71%) (2Y59) (30Y420) (10Y1800) (1Y40) (5%) (1%) (1%) (38%)
0.91* 0.09† 0.17* G0.001‡ 0.2*
G0.001§
0.17* 0.004¶ 0.23* G0.001# G0.001** G0.001§ G0.001†† 0.23* G0.001§§ 0.01||||
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.42; T2 vs T3, P = 0.19; T1 vs T3, P = 0.03. ‡T1 vs T2, P = 0.12; T2 vs T3, P = 0.01; T1 vs T3, P G 0.001. §T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ||Including 1 conversion from vaginal to open surgery. ¶T1 vs T2, P = 0.001; T2 vs T3, P = 0.14; T1 vs T3, P = 0.03. #T1 vs T2, P = 0.01; T2 vs T3, P G 0.001; T1 vs T3, P = 0.09. **T1 vs T2, P G 0.001; T2 vs T3, P = 0.03; T1 vs T3, P G 0.001. ††T1 vs T2, P = 0.06; T2 vs T3, P = 0.06; T1 vs T3, P G 0.001. ‡‡Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 §§T1 vs T2, P = 0.003; T2 vs T3, P = 0.02; T1 vs T3, P G 0.001. ||||T1 vs T2, P = 0.004; T2 vs T3, P = 0.53; T1 vs T3, P = 0.02. BMI, Body mass index; LND, lymphadenectomy (including pelvic and/or para-aortic lymphadenectomy).
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
743
International Journal of Gynecological Cancer
Bogani et al
Baseline characteristics and perioperative surgical outcomes of patients undergoing surgery in the 3 study periods are reported in Table 1. The utilization of laparoscopic approach increased dramatically (from 10% in T1 to 82% in T3; P G 0.001 for trend); whereas the need to perform open surgery decreased over the years (from 83% in T1 to 10% in T3; P G 0.001 for trend). Vaginal approach was nearly stable (from 7% in T1 to 8% in T3; P = 0.76 for trend) through the study period. Overall, we observed a marked reduction in estimated blood loss, length of hospital stay, as well as postoperative complications over the years (P G 0.001). Additionally, a significant decrease in the need of blood transfusion was observed (from 14% in T1 to 5% in T3; P G 0.001). Overall, operative time increased from T1 to T2 (P = 0.01), but decreased in T3 (T1 vs T3, P = 0.09; T2 vs T3, P G 0.001). Eight (2%) patients undergoing laparoscopic approach were converted to open surgery. Conversion rate was 0%, 2%, and
& Volume 25, Number 4, May 2015
2% in T1, T2, and T3, respectively (P = 0.17). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P = 0.23). No surgery-related postoperative death occurred. Details about surgery-related complications are listed in Table 2. We observed similar results analyzing separately endometrial (Table 3), cervical (Table 4), and adnexal (Table 5) cancers. Four (1%), 2 (2%), and 2 (4%) conversions from laparoscopic to open approach were recorded for patients undergoing surgery for endometrial, cervical, and ovarian cancer, respectively (P = 0.50). Additionally, 1 (3%) endometrial cancer patient undergoing vaginal hysterectomy was converted to open approach due to technical issues. Overall, mean (SD) follow-up for alive patients was 105.9 (48.3), 79.2 (31.4), and 40.9 (15.3) months, respectively (P G 0.001). Adjuvant treatment administration rate was 26%, 37%, and 75% for endometrial, cervical, and ovarian cancer, respectively. No between-group differences in 5-year disease free and overall
TABLE 2. Surgery-related complications
Patients who had intraoperative complications Type of complication* Bowel injury Ureter injury Bladder injury Vessels injury Other
Ureteral complications Hemorrhagic complications Wound complications Vaginal cuff complications
Other
T2 (2004-2007), n = 232
T3 (2008-2011), n = 300
5 (2%)
7 (3%)
3 (1%)
1 (endometrial cancer) 1 (endometrial cancer) 1 (endometrial cancer)
1 (endometrial cancer) 1 (endometrial cancer) 1 (ovarian cancer) 1 (cervical cancer) 1 (endometrial cancer) 1 (endometrial cancer) 1 (cervical cancer) 9 (4%)
1 (endometrial cancer) 0 1 (endometrial cancer)
1 (cervical cancer) 1 (cervical cancer)
Patients who had postoperative complications† Type of complication* Lymphatic complications Bowel complications
Abscess Fistula
T1 (2000-2003), n = 204
23 (11%) 2 (cervical cancer) 2 (endometrial cancer) 3 (cervical cancer) 0 1 (endometrial cancer) 1 (cervical cancer) 6 (endometrial cancer) 2 (cervical cancer) 1 (endometrial cancer) 1 (cervical cancer) 1 (cervical cancer) 0 4 (endometrial cancer) 1 (cervical cancer)
1 (cervical cancer) 0 3 (1%)
1 (cervical cancer) 0
0 0
2 (cervical cancer) 1 (cervical cancer) 1 (ovarian cancer) 1 (endometrial cancer)
0 2 (endometrial cancer)
1 (cervical cancer)
1 (endometrial cancer) 1 (cervical cancer) 0 0
0 1 (endometrial cancer) 1 (cervical cancer) 1 (cervical cancer)
0
0
*Type of complication indicates complication (surgical indication); patients may have more than 1 complication. †Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24
744
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
TABLE 3. Changes in endometrial cancer management T1 (2000-2003), n = 145 T2 (2004-2007), n = 153 T3 (2008-2011), n = 195 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Endometrioid Nonendometrioid FIGO grade 1 and 2 3 FIGO stage I 9II Approach Open surgery Laparoscopy Vaginal surgery Conversions LND (PL T PA LND) Lymph node count Positive lymph nodes Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications‡‡ Readmissions Adjuvant therapy Radiotherapy Chemotherapy Combined regimen
65 28.2 83 6
(34Y93) (19Y68) (57%) (4%)
68 27.2 74 10
(38Y90) (19Y46) (48%) (7%)
65 28 94 28
(30Y92) (15.8Y50.8) (48%) (14%)
P 0.02* 0.39† 0.19† 0.003‡
127 (88%) 18 (12%)
132 (86%) 21 (14%)
167 (86%) 28 (14%)
0.87†
115 (79%) 30 (21%)
104 (68%) 49 (32%)
146 (75%) 49 (25%)
0.07§
120 (83%) 25 (17%)
120 (78%) 33 (22%)
168 (86%) 27 (14%)
0.16†
114 (79%) 19 (13%) 12 (8%) 0 (0%) 74 (51%) 17 (3Y60) 12 (17%) 125 (25Y330) 200 (10Y1400) 6 (1Y34) 13 (9%) 3 (2%) 14 (10%) 8 (6%) 33 (23%) 21 (64%) 8 (24%) 4 (12%)
51 (33%) 95 (62%) 7 (5%) 3 (2%) 105 (69%) 16 (5Y39) 13 (12%) 150 (30Y375) 100 (10Y2000) 3 (1Y20) 13 (8%) 4 (3%) 3 (2%) 3 (2%) 49 (32%) 28 (57%) 13 (27%) 8 (16%)
17 158 20 2¶ 114 18 9 115 100 2 10 2 2 3 47 23 21 3
(9%) (81%) (10%) (1%) (58%) (2Y40) (8%) (30Y300) (10Y1800) (1Y19) (5%) (1%) (1%) (2%) (24%) (49%) (44%) (6%)
G0.001||
0.22† 0.007# 0.56† 0.26† G0.001** G0.001†† G0.001|| 0.32† 0.53† G0.001§§ 0.06† 0.14† 0.41† 0.08† 0.31†
*T1 vs T2, P = 0.007; T2 vs T3, P = 0.04; T1 vs T3, P = 0.43. †No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). ‡T1 vs T2, P = 0.3; T2 vs T3, P = 0.05; T1 vs T3, P = 0.001. §T1 vs T2, P = 0.03; T2 vs T3, P = 0.18; T1 vs T3, P = 0.36. ||T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ¶One (0.5%) conversion from vaginal to open surgery. #T1 vs T2, P = 0.001; T2 vs T3, P = 0.05; T1 vs T3, P = 0.17. **T1 vs T2, P = 0.002; T2 vs T3, P G 0.001; T1 vs T3, P = 0.003. ††T1 vs T2, P G 0.001; T2 vs T3, P = 0.15; T1 vs T3, P G 0.001. ‡‡Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 §§T1 vs T2, P = 0.004; T2 vs T3, P = 0.46; T1 vs T3, P G 0.001. BMI, Body mass index; FIGO, International Federation of Gynecology and Obstetrics; LND, lymphadenectomy; PA, para-aortic; PL, pelvic.
survivals were observed in endometrial, cervical, and adnexal cancers (P 9 0.05 log-rank test). Five-year survival outcomes are reported in Figure 1. During the 3 periods, no difference in time interval between surgery and recurrences was recorded
among endometrial (P = 0.24), cervical (P = 0.25), and ovarian cancer (P = 0.73) groups. Additionally, site of recurrences was not influenced by the introduction of laparoscopy (P 9 0.05). Among patients undergoing laparoscopy,
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
745
International Journal of Gynecological Cancer
Bogani et al
& Volume 25, Number 4, May 2015
TABLE 4. Changes in cervical cancer management T1 (2000-2003), n = 45 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Squamous Adenocarcinoma Other Grade G1 and 2 G3 Stage of disease‡ Early stage Locally advanced stage after NACT Approach Laparoscopy Open surgery Vaginal Conversions Type of hysterectomy25 A/B C/D LND (PL T PA LND) Lymph node count Positive nodes Parametrial width, mm# Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications|||| Readmissions Adjuvant therapy
51 (27Y78) 24 (19.6Y52.5) 19 (42%) 0 (0%)
T2 (2004-2007), n = 53
T3 (2008-2011), n = 64
46 23.8 22 2
49 24.2 25 3
(24Y69) (17.4Y39) (41%) (4%)
(23Y77) (15.8Y45.9) (39%) (5%)
P 0.33* 0.55* 0.93* 0.35*
38 (85%) 6 (13%) 1 (2%)
44 (83%) 5 (9%) 4 (8%)
42 (66%) 19 (30%) 3 (4%)
0.03†
32 (71%) 13 (29%)
34 (64%) 19 (36%)
49 (77%) 15 (23%)
0.33*
36 (80%) 9 (20%)
40 (75%) 13 (25%)
47 (73%) 17 (27%)
0.72*
1 (2%) 42 (93%) 2 (4%) 0 (0%)
31 (59%) 22 (41%) 0 (0%) 1 (2%)
53 (83%) 8 (12%) 3 (5%) 1 (2%)
G0.0001§
11 (25%) 34 (75%) 38 (84%) 35 (5Y56) 14 (31%) 3.5 (1.4Y6) 285 (70Y930) 400 (100Y2000) 9 (6Y15) 15 (33%) 2 (4%) 9 (20%) 6 (13%) 14 (31%)
11 42 46 20 10 3.4 282 300 5 5 2 5 4 23
(11%) (79%) (87%) (12Y53) (19%) (1Y7) (65Y375) (10Y1000) (2Y14) (9%) (4%) (9%) (8%) (43%)
10 54 57 22 23 3.5 220 200 4 3 1 1 2 28
(16%) (84%) (89%) (3Y37) (36%) (0.7Y7) (30Y320) (30Y1200) (1Y9) (4%) (2%) (2%) (3%) (42%)
0.66* 0.51* 0.78* G0.001|| 0.12¶ 0.64* G0.001** G0.001†† G0.001‡‡ G0.001§§ 0.65* 0.005¶¶ 0.12* 0.02##
(Continued on next page)
746
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
TABLE 4. (Continued)
T1 (2000-2003), n = 45 Radiotherapy Chemotherapy Combined regimen
9 (64%) 1 (7%) 3 (21%)
T2 (2004-2007), n = 53 17 (75%) 5 (22%) 3 (13%)
T3 (2008-2011), n = 64 19 (68%) 3 (11%) 6 (21%)
P 0.81* 0.88* 0.70*
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.43; T2 vs T3, P = 0.02; T1 vs T3, P = 0.09. ‡Stages of disease were divided in early stage (IA, IB1, and IIA G 4 cm) and locally advanced stage (IB2, IIA 9 4 cm, IIB, and III).3 §T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ||T1 vs T2, P G 0.001; T2 vs T3, P = 0.83; T1 vs T3, P G 0.001. ¶T1 vs T2, P = 0.16; T2 vs T3, P = 0.04; T1 vs T3, P = 0.6. #Details of parametrial width were available for 12 (27%), 20 (38%), and 40 (63%) patients undergoing surgery between T1, T2, and T3, respectively. **T1 vs T2, P = 0.93; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ††T1 vs T2, P = 0.02; T2 vs T3, P = 0.08; T1 vs T3, P G 0.001. ‡‡T1 vs T2, P G 0.001; T2 vs T3, P = 0.22; T1 vs T3, P G 0.001. §§T1 vs T2, P = 0.003; T2 vs T3, P = 0.31; T1 vs T3, P G 0.001. ||||Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 ¶¶T1 vs T2, P = 0.13; T2 vs T3, P = 0.05; T1 vs T3, P = 0.001. ##T1 vs T2, P = 0.01; T2 vs T3, P = 0.96; T1 vs T3, P = 0.009. BMI, Body mass index; G, grade; LND, lymphadenectomy; NACT, neoadjuvant chemotherapy; PA, para-aortic; PL, pelvic.
no port site metastasis occurred; although a patient who underwent open abdominal staging for endometrial cancer developed an incisional recurrence in the site of laparotomic scar. In the endometrial cancer group, vaginal (4% in T1, 2% in T2, and 2% in T3; P = 0.33), lymphatic (1% in T1, 2% in T2, and 2% in T3; P = 0.89), and distant (3% in T1, 5% in T2, and 2% in T3; P = 0.15) recurrences rate were stable over the study period. Similarly, no difference was recorded among cervical (local recurrence: 8% in T1, 7% in T2, and 6% in T3; P = 0.87; regional recurrence: 6% in T1, 4% in T2, and 6% in T3; P = 0.78; distant recurrence: 8% in T1, 5% in T2, and 4% in T3; P = 0.65) and ovarian cancer patients (regional recurrence: 0% in T1, 7% in T2, and 0% in T3; P = 0.11; distant recurrence: 21% in T1, 15% in T2, and 5% in T3; P = 0.16).
DISCUSSION The present study described how the introduction of laparoscopic surgery has modified the treatment of women affected by gynecologic malignancies into an existing oncologic practice, thus demonstrating a number of noteworthy findings. First, we showed a marked trend in the implementation of laparoscopic approach into a clinical setting, suggesting the concrete applicability of laparoscopic surgery. Second, our data showed an improvement in perioperative results over the years, underlying the increased confidence with minimally invasive techniques. Third, our findings showed the effectiveness and the long-term safety of laparoscopy in the management of apparent early stage gynecological malignancies. A growing number of publications have shown that minimally invasive surgery achieves the goals of safety,
feasibility, and effectiveness.1,13Y15 However, only limited evidence, suggesting how these results could be translated into the clinical practice, is available.7,16Y18 In fact, what happened in the clinical setting ‘‘beyond the data of clinical trials’’ is not clear.7 In 1998, Jennings et al,16 comparing patients undergoing surgery in the years 1990 to 1991 with the years 1993 to 1994 (before and after the implementation of laparoscopy in 1992), reported that the utilization of laparoscopy was increased 14-fold for patients affected by gynecological cancer. Albeit they introduced laparoscopy in a selected population, excluding patients who needed radical pelvic surgery or complex surgical procedures, they observed an overall improvement in length of stay, without the increase of surgical-related complications.16 However, several years later, only few studies evaluated how the introduction of laparoscopic approach modified workloads and clinical practices.17,18 Although they agree in underlining the improvement of surgical-related outcomes, it is often difficult to evaluate the formal inclusion criteria for undergoing laparoscopy rather than open surgery and the degree for which laparoscopy was introduced into different clinical settings. In fact, generally, the choice to perform open abdominal versus minimally invasive treatment relies on discretion of the attending surgeons and it was not driven by specific guidelines.17 As aforementioned, in 2009, we reported how the use of laparoscopy modified our practice. We already observed a marked decrease in the need to perform open surgery and an improvement of perioperative results, although short-term term oncologic outcomes were not influenced by the introduction of minimally surgery.7 The present study supports our
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
747
International Journal of Gynecological Cancer
Bogani et al
& Volume 25, Number 4, May 2015
TABLE 5. Changes in ovarian cancer management
Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Epithelial Nonepithelial Grade (for epithelial tumor) G1 and 2 G3 FIGO stage I 9II Approach Laparoscopy Open surgery Conversions LND (PL+ PA LND) Lymph node count Positive lymph node Cysts rupture Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications** Readmission Adjuvant therapy (chemotherapy)
T1 (2000-2003), n = 14
T2 (2004-2007), n = 26
T3 (2008-2011), n = 41
54 (40Y82) 23.1 (18.8Y35.6) 4 (28%) 0 (0%)
56 24.2 10 2
55 21.8 14 5
(13Y76) (18Y33.7) (38%) (8%)
(20Y80) (16.6Y39.2) (34%) (12%)
P 0.75* 0.15† 0.81* 0.36*
11 (79%) 3 (21%)
24 (92%) 2 (8%)
39 (95%) 2 (5%)
0.16*
5 (45%) 6 (55%)
9 (38%) 15 (62%)
15 (38%) 24 (62%)
0.89*
10 (71%) 4 (29%)
17 (65%) 9 (35%)
22 (54%) 19 (46%)
0.41*
1 (7%) 13§ (93%) 0 14 (100%) 20 (8Y37) 1 (7%) 3 (21%) 136.3 (95Y280) 400 (100Y700) 6 (3Y11) 1 (7%) 0 (0%) 0 (0%) 1 (7%) 9 (64%)
15 (60%) 11 (40%) 0 26 (100%) 27 (8-58) 4 (15%) 1 (4%) 325 (115Y480) 300 (50Y3000) 6 (2Y30) 2 (8%) 1 (4%) 1 (4%) 0 (0%) 22 (85%)
36 (88%) 5 (12%) 2 (5%) 41 (100%) 30 (10Y59) 9 (22%) 4 (10%) 267 (105Y420) 275 (50Y1000) 4 (1-12) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 38 (93%)
G0.001‡ 0.99* 90.99* 0.04|| 0.42* 0.2* G0.001¶ 0.32* 0.01# 0.57* 0.34* 0.34* 0.39* 0.03††
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.83; T2 vs T3, P = 0.04; T1 vs T3, P = 0.69. ‡T1 vs T2, P = 0.001; T2 vs T3, P = 0.01; T1 vs T3, P G 0.001. §Two patients had diagnostic laparoscopy followed by open staging after the diagnosis of invasive ovarian cancer before we started to perform laparoscopy for ovarian cancer. ||T1 vs T2, P = 0.07; T2 vs T3, P = 0.54; T1 vs T3, P = 0.002. ¶T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P = 0.04. #T1 vs T2, P = 0.69; T2 vs T3, P = 0.01; T1 vs T3, P = 0.06. **Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 ††T1 vs T2, P = 0.14; T2 vs T3, P = 0.29; T1 vs T3, P = 0.009. BMI, Body mass index; FIGO, International Federation of Gynecology and Obstetrics; LND, lymphadenectomy; PA, para-aortic; PL, pelvic.
preliminary results in a larger population and it reports longterm outcomes, thus confirming the effectiveness of minimally invasive surgery. Once the operative and postoperative safety of laparoscopic approach are established, the following are the 2 main critics on its introduction into a preexisting clinical setting: (1)
748
The ‘‘steep learning curve’’ of laparoscopy with potential increase in surgical-related complication rate and longer operative time of a ‘‘new’’ technique. However, as reported by our study group7 and other authors,16Y19 the introduction of laparoscopy is not related to an increased number of complications; on the contrary, the overall complication rate * 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
FIGURE 1. Five-year survival outcomes. Five-year disease free (DFS) and overall survivals (OS) for endometrial, cervical, and adnexal cancers, undergoing surgery in the study period 2000 to 2003 (T1), 2004 to 2007 (T2), and 2008 to 2011 (T3). decreases.7 Similarly, operative time, after an initial increase (from T1 to T2) decreases over the study period (from T2 to T3). These figures reflect the gradual implementation of laparoscopic surgery in our practice: from simple to even more complex, technically challenging procedures over the years. (2) One might expect that the longer operative time needed to perform a procedure via laparoscopic rather than open surgery may lead to a reduction of the whole workload. However, we observed that the number of patients who presented at our unit increases dramatically over the years (from 209 in T1 to 302 in T3; approximately +50%). Three main causes could explain this as follows: first, albeit the prediction, overall operative time decreased; second, the shorter hospital stay and the lower rate of complication rate promoted a more rapid turnover of patients; and third, laparoscopy increased patients’ appealing. These latter aspects are also paramount in the perspective of a policy of cost saving. The utilization of reusable instrumentations, the minimized operative time, minimized length of stay, as well as the minimized transfusion and postoperative complication rates potentially concur in the reduced amount of money spent, over the years.26Y28 Moreover, our survival analysis showed that the embrace of laparoscopic approach does not influence oncologic outcomes. However, these results have to be interpreted with caution because groups are not homogeneous in terms of adjuvant therapy administration rate and disease characteristics. Additional limitations of this study include the inherent biases of a retrospective, single-center study design. However, the inclusion of consecutive patients with apparent organ-confined tumors reduces selection and publication biases. In fact, at the beginning of our experience, surgeons had no specific skills in laparoscopy surgery, thus supporting
the reproducibility of our results in other clinical settings. In addition, the main merit of our study is to report one of the larger series of gynecological malignancies managed with laparoscopy from a single institution. In conclusion, the present study indicates the feasibility of the gradual implementation of laparoscopic approach in the management of apparent early stage gynecological malignancies. We observed that through the introduction of laparoscopy, we can reduce the length of stay, complication, and blood transfusion rates, without neglecting medium-term outcomes, thus improving standard of care of patients affected by gynecological cancers. Further attempts are needed to reduce the rate of unnecessary open procedures, thus improving both patients’ care and workload.
REFERENCES 1. How J, Lau S, Press J, et al. Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study. Gynecol Oncol. 2012;127:332Y337. 2. Lavoue V, Zeng X, Lau S, et al. Impact of robotics on the outcome of elderly patients with endometrial cancer. Gynecol Oncol. 2014;133:556Y562. 3. Bogani G, Cromi A, Uccella S, et al. Nerve-sparing vs. conventional laparoscopic radical hysterectomy: a minimum 12 months follow-up study. Int J Gynecol Cancer. 2014;24:787Y793. 4. Kaushik S, Akhter K, Rufford B, et al. The use of laparostomy in patients with gynecologic cancer: first report from a UK cancer center. Int J Gynecol Cancer. 2013;23:951Y955. 5. Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
749
Bogani et al
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
International Journal of Gynecological Cancer
uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30:695Y700. Wright JD, Herzog TJ, Neugut AI, et al. Comparative effectiveness of minimally invasive and abdominal radical hysterectomy for cervical cancer. Gynecol Oncol. 2012;127:11Y17. Ghezzi F, Cromi A, Uccella S, et al. Incorporating laparoscopy in the practice of a gynecologic oncology service: actual impact beyond clinical trials data. Ann Surg Oncol. 2009;16:2305Y2314. Fader AN, Seamon LG, Escobar PF, et al. Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers. Gynecol Oncol. 2012;126:180Y185. Vaknin Z, Perri T, Lau S, et al. Outcome and quality of life in a prospective cohort of the first 100 robotic surgeries for endometrial cancer, with focus on elderly patients. Int J Gynecol Cancer. 2010;20:1367Y1373. Leitao MM Jr, Briscoe G, Santos K, et al. Introduction of a computer-based surgical platform in the surgical care of patients with newly diagnosed uterine cancer: outcomes and impact on approach. Gynecol Oncol. 2012;125:394Y399. ElSahwi KS, Hooper C, De Leon MC, et al. Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer. Gynecol Oncol. 2012;124:260Y264. Dowdy SC, Aletti G, Cliby WA, et al. Extra-peritoneal laparoscopic para-aortic lymphadenectomyVa prospective cohort study of 293 patients with endometrial cancer. Gynecol Oncol. 2008;111:418Y424. Bogani G, Cromi A, Uccella S, et al. Peri-operative and long-term outcomes of laparoscopic, open abdominal and vaginal surgery for endometrial cancer in patients aged 80 years or more. Int J Gynecol Cancer. 2014;24:894Y900. Ghezzi F, Cromi A, Siesto G, et al. Use of laparoscopy in older women undergoing gynecologic procedures: is it time to overcome initial concerns? Menopause. 2010;17:96Y103. Bogani G, Cromi A, Serati M, et al. Predictors of postoperative morbidity after laparoscopic versus open radical hysterectomy plus external beam radiotherapy: a propensity-matched comparison. J Surg Oncol. 2014;110:893Y898. Jennings TS, Dottino P, Rahaman J, et al. Results of selective use of operative laparoscopy in gynecologic oncology. Gynecol Oncol. 1998;70:323Y328.
750
& Volume 25, Number 4, May 2015
17. Chi DS, Abu-Rustum NR, Sonoda Y, et al. Ten-year experience with laparoscopy on a gynecologic oncology service: analysis of risk factors for complications and conversion to laparotomy. Am J Obstet Gynecol. 2004;191:1138Y1145. 18. Barakat RR, Lev G, Hummer AJ, et al. Twelve-year experience in the management of endometrial cancer: a change in surgical and postoperative radiation approaches. Gynecol Oncol. 2007;105:150Y156. 19. Fagotti A, Vizzielli G, Fanfani F, et al. Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience. Gynecol Oncol. 2013;131:341Y346. 20. Bogani G, Cromi A, Serati M, et al. Laparoscopic and open abdominal staging for early stage ovarian cancer: our experience, systematic review and meta-analysis of comparative studies. Int J Gynecol Cancer. 2014;24:1241Y1249. 21. Bogani G, Cromi A, Uccella S, et al. Laparoscopic staging in women older than 75 years with early-stage endometrial cancer: comparison with open surgical operation. Menopause. 2014;21:945Y951. 22. Ghezzi F, Cromi A, Uccella S, et al. Transumbilical versus transvaginal retrieval of surgical specimens at laparoscopy: a randomized trial. Am J Obstet Gynecol. 2012;207:112.e1Y112.e6. 23. Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol. 2008;9:297Y303. 24. Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250:177Y186. 25. Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803Y813. 26. Dowdy SC, Borah BJ, Bakkum-Gamez JN, et al. Factors predictive of postoperative morbidity and cost in patients with endometrial cancer. Obstet Gynecol. 2012;120:1419Y1427. 27. Barnett JC, Judd JP, Wu JM, et al. Cost comparison among robotic, laparoscopic, and open hysterectomy for endometrial cancer. Obstet Gynecol. 2010;116:685Y693. 28. Lau S, Vaknin Z, Ramana-Kumar AV, et al. Outcomes and cost comparisons after introducing a robotics program for endometrial cancer surgery. Obstet Gynecol. 2012;119:717Y724.
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
Improving Standard of Care Through Introduction of Laparoscopy for the Surgical Management of Gynecological Malignancies Giorgio Bogani, MD,* Antonella Cromi, PhD,* Maurizio Serati, MD,* Edoardo Di Naro, MD,Þ Jvan Casarin, MD,* Ciro Pinelli, MD,* Ilario Candeloro, MD,* Davide Sturla, MD,* and Fabio Ghezzi, MD*
Objective: This study aimed to evaluate the impact on perioperative and medium-term oncologic outcomes of the implementation of laparoscopy into a preexisting oncologic setting. Methods: Data from consecutive 736 patients undergoing surgery for apparent early stage gynecological malignancies (endometrial, cervical, and adnexal cancers) between 2000 and 2011 were reviewed. Complications were graded per the Accordion classification. Survival outcomes within the first 5 years were analyzed using Kaplan-Meier method. Results: Overall, 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery via laparoscopy through the years (from 10% in the years 20002003 to 82% in years 2008-2011; P G 0.001 for trend); while the need to perform open surgery decreased dramatically (from 83% to 10%; P G 0.001). Vaginal approach was nearly stable over the years (from 7% to 8%; P = 0.76). A marked reduction in estimated blood loss, length of hospital stay, blood transfusions as well as grade greater than or equal to 3 postoperative complications over the years was observed (P G 0.001). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P 9 0.05). The introduction of laparoscopy did not adversely affect medium-term (within 5 years) survival outcomes of patients undergoing surgery for apparent early stage cancers of the endometrium, uterine cervix, and adnexa (P 9 0.05 log-rank test). Conclusions: The introduction of laparoscopy into a preexisting oncologic service allows an improvement of standard of care due to a gain in perioperative results, without detriments of medium-term oncologic outcomes. Key Words: Laparoscopy, Endometrial cancer, Cervical cancer, Ovarian cancer, Survival Received April 20, 2014, and in revised form January 4, 2015. Accepted for publication January 4, 2015. (Int J Gynecol Cancer 2015;25: 741Y750)
represents the mainstay of treatment for women S urgery affected by gynecological malignancies. During the past
2 decades, technical and technological innovations have
brought a new frontier in cancer treatments.1Y3 In particular, the introduction of laparoscopic surgery has profoundly changed the approach to cancers’ treatments. Historically,
*Department of Obstetrics and Gynecology, University of Insubria, Varese; and †Department of Obstetrics and Gynecology, University of Bari, Bari, Italy. Copyright * 2015 by IGCS and ESGO ISSN: 1048-891X DOI: 10.1097/IGC.0000000000000406
Address correspondence and reprint requests to Giorgio Bogani, MD, Department of Obstetrics and Gynecology, University of Insubria, Piazza Biroldi, 1, Varese 21100, Italy. E-mail: [email protected]. The authors declare no conflicts of interest.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
741
Bogani et al
International Journal of Gynecological Cancer
curative cancer surgery was ‘‘macrosurgery,’’ for which long abdominal incision and intra-abdominal organ manipulations were mandatory requirements.4 Then, in recent years, surgical oncology practice has evolved gradually; minimally invasive surgery continues to emerge in each surgical field and evolve as new technology develops.3,5 Albeit high levels of evidence support the use of laparoscopic approach (at least for the treatment of endometrial cancer), the embrace of laparoscopy in the treatment of gynecological malignancies seems to evolve slower than as expected.6 In fact, although several studies have shown that laparoscopy overcomes open surgery for both short-term7Y14 and long-term outcomes,15 what really the introduction of laparoscopy has changed into the clinical practice is far from clear. In fact, only limited data showing the degree of the shift from open abdominal to minimally invasive surgery into the clinical practice are available.7,16Y19 Hence, it is difficult to estimate what really happened in the setting of routine workload rather than the context of clinical trials. In 2009, we reported how the introduction of laparoscopy has influenced our practice.7 Five years later, we sought to analyze how the implementation of laparoscopic surgery has modified our routine practice. We aimed to describe our experience, reporting perioperative as well as long-term outcomes of consecutive patients undergoing surgical treatment for gynecological malignancies, thus allowing analyzing the impact of laparoscopy in a concrete clinical setting.
MATERIALS AND METHODS We retrospectively reviewed data of consecutive patients undergoing surgical treatment for early stage cancer of the endometrium, uterine cervix, and adnexa between January 1, 2000, and December 31, 2011, at the Department of Gynecology of University of Insubria (department A) and the Department of Obstetrics and Gynecology-Ospedale di Circolo Fondazione Macchi (department B). Both the departments are located in the same hospital in Varese (Italy) and they become a single Gynecologic Oncology Unit since 2010. In our institutions, research activities involving the study of existing data are exempt from the requirement for institutional review board approval. For the purpose of this study, patients affected by tumors (ie, molar disease, vulvar cancer) for which the use of open abdominal/laparoscopic surgery is generally not applicable were excluded.7 Patients were allocated in 3 groups according their malignancy (endometrial, cervical, and adnexal cancers). Low malignant potential ovarian tumors were not included, because their presence could impair the analysis, improving surgical and survival outcomes. In case of synchronous tumors, patients were allocated in the group considered at higher risk (ie, patients with synchronous adnexal and uterine cancer were allocated in the adnexal cancer group). Early stage of disease was defined as organ-confined cancer, with the absence of macroscopic gross intra-abdominal disease. In 2002, 2003, and 2004, we started a policy of systematic implementation of laparoscopic staging for uterine corpus, malignant ovarian, and cervical cancers, respectively.7 Detailed descriptions of surgical technique are reported elsewhere.3,7,20Y23 Laparoscopic devices (including trocars,
742
& Volume 25, Number 4, May 2015
laparoscopic instruments, and uterine manipulator (RUMIKoh) were for mostly reusable.3 Usually, disposable vessels sealing devices were not used. After the implementation of minimal access surgery, laparoscopic approach was attempted in all women who presented to our institution, unless specific contraindications to laparoscopic surgery existed, such as documented severe cardiopulmonary disease. No patient was refused laparoscopy for reasons of uterus size, age, obesity, prior surgical history, or anticipated difficulty of resection. Active attempts were used to decrease the risk of intra-abdominal spillage and loss of surgical debris.7,22 The same team of surgeons, who were assisted by residents and trainees, performed all surgical procedures. Data concerning the surgical procedures, postoperative details, adjuvant therapy as well as follow-up evaluations were recorded prospectively in our computerized oncologic database, a research-quality database maintained by trained residents and updated on a regular basis. Data including age, body mass index, and medical/surgical history were abstracted retrospectively. Comorbidity levels were assessed using the Charlson comorbidity index.21 To evaluate changes in the management of cancer patients, 3 study periods were analyzed: T1 (2000-2003), in which laparoscopic surgery was first introduced but open surgery represented the standard of care; T2 (2004-2007), in which we assisted at a systematic implementation of laparoscopic surgery; and T3 (2008-2011), in which laparoscopic surgery was the standard of care. During the study period, there were no significant differences in patients’ care for each surgical technique. Interventions were performed under general endotracheal anesthesia. Operative times were recorded from the first skin incision to the last suture (skin to skin). Blood loss was estimated from the contents of suction devices. Hospital stay was counted from the first postoperative day. Organ damage, blood transfusion, and the need to conversion to laparotomy (for women who had laparoscopic surgery) were considered as intraoperative complications. Postoperative complications were graded per the Accordion Severity System.24 For the purpose of this study, only grade greater than or equal to 3 complications, occurred within the first 8 weeks after surgery, were reported. Martin criteria were applied to improve quality in complications reporting.25 Readmissions (for more than 24 hours) that occurred within 8 weeks were reported. Adjuvant therapy (radiotherapy and/or chemotherapy) was delivered according to diseases and clinical protocols.7 Follow-up evaluations, with pelvic examination and ultrasound examination, were planned according to institutional protocols.3,7,13 Dates and sites of recurrence were recorded. Recurrences were classified in local (vaginal), regional (lymphatic), and distant. Patients were considered by intention to treat principle. Hence, for statistical purpose, patients who had conversion from laparoscopy or vaginal to surgery to open were considered in the laparoscopic and vaginal group, respectively. Statistical analysis was performed with GraphPad Prism version 6.0 for Mac (GraphPad Software, San Diego, CA). Normality testing (D’Agostino and Pearson test) was performed to determine whether data were sampled from a Gaussian distribution. * 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
One-way analysis of variance and Kruskal-Wallis test were performed to compare 3 or more groups of continuous parametric and nonparametric variables, respectively. The W2 test was used to analyze proportions. Incidence of events between 2 groups was analyzed for statistical significance by using the Fisher exact test. Odds ratio and 95% confidence intervals were calculated for each comparison. When we evaluated only 2 groups, t test and Mann-Whitney U test were used to compare continuous parametric and nonparametric variables, respectively. Disease-free and overall survivals within 5 years were estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Trends over the times for continuous variables and proportions were assessed using
Laparoscopy for Gynecological Cancers
posttest for linear trend and W2, respectively. P values less than 0.05 were considered statistically significant.
RESULTS Overall, 736 patients undergoing surgical treatment for gynecological malignancies between January 1, 2000, and December 31, 2011, were available for the analysis: 493 (67%), 162 (22%), and 81 (11%) had surgery for apparent early stage endometrial, cervical, and adnexal cancer. We assisted at an increase of the number of patients undergoing surgery through the years (from 204 in T1 to 300 in T3; +50%); whereas the percentages of endometrial, cervical, and adnexal cancers were stable over the whole study period (P 9 0.05).
TABLE 1. Changes in gynecological malignancies management P
T1 (2000-2003), n = 204 T2 (2004-2007), n = 232 T3 (2008-2011), n = 300 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Gynecological cancer Endometrium Uterine cervix Adnexa Approach Open abdominal Laparoscopic Vaginal Conversion LND (PL T PA LND) Lymph node count Operative time, min Estimated blood loss, mL Hospital stay, d Transfusion Intraoperative complications Postoperative complication‡‡ Adjuvant therapy
61 27 106 6
(27Y93) (18.8Y68) (52%) (3%)
64 26.8 106 14
(13Y90) (17.4Y46) (46%) (6%)
62 26.2 131 36
(20Y92) (15.8Y50.8) (44%) (12%)
145 (71%) 45 (22%) 14 (7%)
153 (66%) 53 (23%) 26 (11%)
195 (65%) 64 (21%) 41 (14%)
169 (83%) 21 (10%) 14 (7%) 0 (0%) 126 (62%) 20 (3Y60) 150 (25Y930) 200 (10Y2000) 6 (1Y34) 29 (14%) 5 (2%) 23 (11%) 56 (27%)
85 (36%) 140 (60%) 7 (3%) 4 (2%) 177 (76%) 19 (5Y58) 185 (30Y480) 150 (10Y3000) 4 (1Y30) 20 (9%) 7 (3%) 9 (4%) 94 (41%)
31 248 21 5|| 212 20 135 150 2 14 3 3 113
(10%) (82%) (8%) (2%) (71%) (2Y59) (30Y420) (10Y1800) (1Y40) (5%) (1%) (1%) (38%)
0.91* 0.09† 0.17* G0.001‡ 0.2*
G0.001§
0.17* 0.004¶ 0.23* G0.001# G0.001** G0.001§ G0.001†† 0.23* G0.001§§ 0.01||||
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.42; T2 vs T3, P = 0.19; T1 vs T3, P = 0.03. ‡T1 vs T2, P = 0.12; T2 vs T3, P = 0.01; T1 vs T3, P G 0.001. §T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ||Including 1 conversion from vaginal to open surgery. ¶T1 vs T2, P = 0.001; T2 vs T3, P = 0.14; T1 vs T3, P = 0.03. #T1 vs T2, P = 0.01; T2 vs T3, P G 0.001; T1 vs T3, P = 0.09. **T1 vs T2, P G 0.001; T2 vs T3, P = 0.03; T1 vs T3, P G 0.001. ††T1 vs T2, P = 0.06; T2 vs T3, P = 0.06; T1 vs T3, P G 0.001. ‡‡Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 §§T1 vs T2, P = 0.003; T2 vs T3, P = 0.02; T1 vs T3, P G 0.001. ||||T1 vs T2, P = 0.004; T2 vs T3, P = 0.53; T1 vs T3, P = 0.02. BMI, Body mass index; LND, lymphadenectomy (including pelvic and/or para-aortic lymphadenectomy).
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
743
International Journal of Gynecological Cancer
Bogani et al
Baseline characteristics and perioperative surgical outcomes of patients undergoing surgery in the 3 study periods are reported in Table 1. The utilization of laparoscopic approach increased dramatically (from 10% in T1 to 82% in T3; P G 0.001 for trend); whereas the need to perform open surgery decreased over the years (from 83% in T1 to 10% in T3; P G 0.001 for trend). Vaginal approach was nearly stable (from 7% in T1 to 8% in T3; P = 0.76 for trend) through the study period. Overall, we observed a marked reduction in estimated blood loss, length of hospital stay, as well as postoperative complications over the years (P G 0.001). Additionally, a significant decrease in the need of blood transfusion was observed (from 14% in T1 to 5% in T3; P G 0.001). Overall, operative time increased from T1 to T2 (P = 0.01), but decreased in T3 (T1 vs T3, P = 0.09; T2 vs T3, P G 0.001). Eight (2%) patients undergoing laparoscopic approach were converted to open surgery. Conversion rate was 0%, 2%, and
& Volume 25, Number 4, May 2015
2% in T1, T2, and T3, respectively (P = 0.17). Surgical radicality assessed lymph nodes count was not influenced by the introduction of laparoscopic approach (P = 0.23). No surgery-related postoperative death occurred. Details about surgery-related complications are listed in Table 2. We observed similar results analyzing separately endometrial (Table 3), cervical (Table 4), and adnexal (Table 5) cancers. Four (1%), 2 (2%), and 2 (4%) conversions from laparoscopic to open approach were recorded for patients undergoing surgery for endometrial, cervical, and ovarian cancer, respectively (P = 0.50). Additionally, 1 (3%) endometrial cancer patient undergoing vaginal hysterectomy was converted to open approach due to technical issues. Overall, mean (SD) follow-up for alive patients was 105.9 (48.3), 79.2 (31.4), and 40.9 (15.3) months, respectively (P G 0.001). Adjuvant treatment administration rate was 26%, 37%, and 75% for endometrial, cervical, and ovarian cancer, respectively. No between-group differences in 5-year disease free and overall
TABLE 2. Surgery-related complications
Patients who had intraoperative complications Type of complication* Bowel injury Ureter injury Bladder injury Vessels injury Other
Ureteral complications Hemorrhagic complications Wound complications Vaginal cuff complications
Other
T2 (2004-2007), n = 232
T3 (2008-2011), n = 300
5 (2%)
7 (3%)
3 (1%)
1 (endometrial cancer) 1 (endometrial cancer) 1 (endometrial cancer)
1 (endometrial cancer) 1 (endometrial cancer) 1 (ovarian cancer) 1 (cervical cancer) 1 (endometrial cancer) 1 (endometrial cancer) 1 (cervical cancer) 9 (4%)
1 (endometrial cancer) 0 1 (endometrial cancer)
1 (cervical cancer) 1 (cervical cancer)
Patients who had postoperative complications† Type of complication* Lymphatic complications Bowel complications
Abscess Fistula
T1 (2000-2003), n = 204
23 (11%) 2 (cervical cancer) 2 (endometrial cancer) 3 (cervical cancer) 0 1 (endometrial cancer) 1 (cervical cancer) 6 (endometrial cancer) 2 (cervical cancer) 1 (endometrial cancer) 1 (cervical cancer) 1 (cervical cancer) 0 4 (endometrial cancer) 1 (cervical cancer)
1 (cervical cancer) 0 3 (1%)
1 (cervical cancer) 0
0 0
2 (cervical cancer) 1 (cervical cancer) 1 (ovarian cancer) 1 (endometrial cancer)
0 2 (endometrial cancer)
1 (cervical cancer)
1 (endometrial cancer) 1 (cervical cancer) 0 0
0 1 (endometrial cancer) 1 (cervical cancer) 1 (cervical cancer)
0
0
*Type of complication indicates complication (surgical indication); patients may have more than 1 complication. †Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24
744
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
TABLE 3. Changes in endometrial cancer management T1 (2000-2003), n = 145 T2 (2004-2007), n = 153 T3 (2008-2011), n = 195 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Endometrioid Nonendometrioid FIGO grade 1 and 2 3 FIGO stage I 9II Approach Open surgery Laparoscopy Vaginal surgery Conversions LND (PL T PA LND) Lymph node count Positive lymph nodes Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications‡‡ Readmissions Adjuvant therapy Radiotherapy Chemotherapy Combined regimen
65 28.2 83 6
(34Y93) (19Y68) (57%) (4%)
68 27.2 74 10
(38Y90) (19Y46) (48%) (7%)
65 28 94 28
(30Y92) (15.8Y50.8) (48%) (14%)
P 0.02* 0.39† 0.19† 0.003‡
127 (88%) 18 (12%)
132 (86%) 21 (14%)
167 (86%) 28 (14%)
0.87†
115 (79%) 30 (21%)
104 (68%) 49 (32%)
146 (75%) 49 (25%)
0.07§
120 (83%) 25 (17%)
120 (78%) 33 (22%)
168 (86%) 27 (14%)
0.16†
114 (79%) 19 (13%) 12 (8%) 0 (0%) 74 (51%) 17 (3Y60) 12 (17%) 125 (25Y330) 200 (10Y1400) 6 (1Y34) 13 (9%) 3 (2%) 14 (10%) 8 (6%) 33 (23%) 21 (64%) 8 (24%) 4 (12%)
51 (33%) 95 (62%) 7 (5%) 3 (2%) 105 (69%) 16 (5Y39) 13 (12%) 150 (30Y375) 100 (10Y2000) 3 (1Y20) 13 (8%) 4 (3%) 3 (2%) 3 (2%) 49 (32%) 28 (57%) 13 (27%) 8 (16%)
17 158 20 2¶ 114 18 9 115 100 2 10 2 2 3 47 23 21 3
(9%) (81%) (10%) (1%) (58%) (2Y40) (8%) (30Y300) (10Y1800) (1Y19) (5%) (1%) (1%) (2%) (24%) (49%) (44%) (6%)
G0.001||
0.22† 0.007# 0.56† 0.26† G0.001** G0.001†† G0.001|| 0.32† 0.53† G0.001§§ 0.06† 0.14† 0.41† 0.08† 0.31†
*T1 vs T2, P = 0.007; T2 vs T3, P = 0.04; T1 vs T3, P = 0.43. †No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). ‡T1 vs T2, P = 0.3; T2 vs T3, P = 0.05; T1 vs T3, P = 0.001. §T1 vs T2, P = 0.03; T2 vs T3, P = 0.18; T1 vs T3, P = 0.36. ||T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ¶One (0.5%) conversion from vaginal to open surgery. #T1 vs T2, P = 0.001; T2 vs T3, P = 0.05; T1 vs T3, P = 0.17. **T1 vs T2, P = 0.002; T2 vs T3, P G 0.001; T1 vs T3, P = 0.003. ††T1 vs T2, P G 0.001; T2 vs T3, P = 0.15; T1 vs T3, P G 0.001. ‡‡Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 §§T1 vs T2, P = 0.004; T2 vs T3, P = 0.46; T1 vs T3, P G 0.001. BMI, Body mass index; FIGO, International Federation of Gynecology and Obstetrics; LND, lymphadenectomy; PA, para-aortic; PL, pelvic.
survivals were observed in endometrial, cervical, and adnexal cancers (P 9 0.05 log-rank test). Five-year survival outcomes are reported in Figure 1. During the 3 periods, no difference in time interval between surgery and recurrences was recorded
among endometrial (P = 0.24), cervical (P = 0.25), and ovarian cancer (P = 0.73) groups. Additionally, site of recurrences was not influenced by the introduction of laparoscopy (P 9 0.05). Among patients undergoing laparoscopy,
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
745
International Journal of Gynecological Cancer
Bogani et al
& Volume 25, Number 4, May 2015
TABLE 4. Changes in cervical cancer management T1 (2000-2003), n = 45 Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Squamous Adenocarcinoma Other Grade G1 and 2 G3 Stage of disease‡ Early stage Locally advanced stage after NACT Approach Laparoscopy Open surgery Vaginal Conversions Type of hysterectomy25 A/B C/D LND (PL T PA LND) Lymph node count Positive nodes Parametrial width, mm# Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications|||| Readmissions Adjuvant therapy
51 (27Y78) 24 (19.6Y52.5) 19 (42%) 0 (0%)
T2 (2004-2007), n = 53
T3 (2008-2011), n = 64
46 23.8 22 2
49 24.2 25 3
(24Y69) (17.4Y39) (41%) (4%)
(23Y77) (15.8Y45.9) (39%) (5%)
P 0.33* 0.55* 0.93* 0.35*
38 (85%) 6 (13%) 1 (2%)
44 (83%) 5 (9%) 4 (8%)
42 (66%) 19 (30%) 3 (4%)
0.03†
32 (71%) 13 (29%)
34 (64%) 19 (36%)
49 (77%) 15 (23%)
0.33*
36 (80%) 9 (20%)
40 (75%) 13 (25%)
47 (73%) 17 (27%)
0.72*
1 (2%) 42 (93%) 2 (4%) 0 (0%)
31 (59%) 22 (41%) 0 (0%) 1 (2%)
53 (83%) 8 (12%) 3 (5%) 1 (2%)
G0.0001§
11 (25%) 34 (75%) 38 (84%) 35 (5Y56) 14 (31%) 3.5 (1.4Y6) 285 (70Y930) 400 (100Y2000) 9 (6Y15) 15 (33%) 2 (4%) 9 (20%) 6 (13%) 14 (31%)
11 42 46 20 10 3.4 282 300 5 5 2 5 4 23
(11%) (79%) (87%) (12Y53) (19%) (1Y7) (65Y375) (10Y1000) (2Y14) (9%) (4%) (9%) (8%) (43%)
10 54 57 22 23 3.5 220 200 4 3 1 1 2 28
(16%) (84%) (89%) (3Y37) (36%) (0.7Y7) (30Y320) (30Y1200) (1Y9) (4%) (2%) (2%) (3%) (42%)
0.66* 0.51* 0.78* G0.001|| 0.12¶ 0.64* G0.001** G0.001†† G0.001‡‡ G0.001§§ 0.65* 0.005¶¶ 0.12* 0.02##
(Continued on next page)
746
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
TABLE 4. (Continued)
T1 (2000-2003), n = 45 Radiotherapy Chemotherapy Combined regimen
9 (64%) 1 (7%) 3 (21%)
T2 (2004-2007), n = 53 17 (75%) 5 (22%) 3 (13%)
T3 (2008-2011), n = 64 19 (68%) 3 (11%) 6 (21%)
P 0.81* 0.88* 0.70*
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.43; T2 vs T3, P = 0.02; T1 vs T3, P = 0.09. ‡Stages of disease were divided in early stage (IA, IB1, and IIA G 4 cm) and locally advanced stage (IB2, IIA 9 4 cm, IIB, and III).3 §T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ||T1 vs T2, P G 0.001; T2 vs T3, P = 0.83; T1 vs T3, P G 0.001. ¶T1 vs T2, P = 0.16; T2 vs T3, P = 0.04; T1 vs T3, P = 0.6. #Details of parametrial width were available for 12 (27%), 20 (38%), and 40 (63%) patients undergoing surgery between T1, T2, and T3, respectively. **T1 vs T2, P = 0.93; T2 vs T3, P G 0.001; T1 vs T3, P G 0.001. ††T1 vs T2, P = 0.02; T2 vs T3, P = 0.08; T1 vs T3, P G 0.001. ‡‡T1 vs T2, P G 0.001; T2 vs T3, P = 0.22; T1 vs T3, P G 0.001. §§T1 vs T2, P = 0.003; T2 vs T3, P = 0.31; T1 vs T3, P G 0.001. ||||Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 ¶¶T1 vs T2, P = 0.13; T2 vs T3, P = 0.05; T1 vs T3, P = 0.001. ##T1 vs T2, P = 0.01; T2 vs T3, P = 0.96; T1 vs T3, P = 0.009. BMI, Body mass index; G, grade; LND, lymphadenectomy; NACT, neoadjuvant chemotherapy; PA, para-aortic; PL, pelvic.
no port site metastasis occurred; although a patient who underwent open abdominal staging for endometrial cancer developed an incisional recurrence in the site of laparotomic scar. In the endometrial cancer group, vaginal (4% in T1, 2% in T2, and 2% in T3; P = 0.33), lymphatic (1% in T1, 2% in T2, and 2% in T3; P = 0.89), and distant (3% in T1, 5% in T2, and 2% in T3; P = 0.15) recurrences rate were stable over the study period. Similarly, no difference was recorded among cervical (local recurrence: 8% in T1, 7% in T2, and 6% in T3; P = 0.87; regional recurrence: 6% in T1, 4% in T2, and 6% in T3; P = 0.78; distant recurrence: 8% in T1, 5% in T2, and 4% in T3; P = 0.65) and ovarian cancer patients (regional recurrence: 0% in T1, 7% in T2, and 0% in T3; P = 0.11; distant recurrence: 21% in T1, 15% in T2, and 5% in T3; P = 0.16).
DISCUSSION The present study described how the introduction of laparoscopic surgery has modified the treatment of women affected by gynecologic malignancies into an existing oncologic practice, thus demonstrating a number of noteworthy findings. First, we showed a marked trend in the implementation of laparoscopic approach into a clinical setting, suggesting the concrete applicability of laparoscopic surgery. Second, our data showed an improvement in perioperative results over the years, underlying the increased confidence with minimally invasive techniques. Third, our findings showed the effectiveness and the long-term safety of laparoscopy in the management of apparent early stage gynecological malignancies. A growing number of publications have shown that minimally invasive surgery achieves the goals of safety,
feasibility, and effectiveness.1,13Y15 However, only limited evidence, suggesting how these results could be translated into the clinical practice, is available.7,16Y18 In fact, what happened in the clinical setting ‘‘beyond the data of clinical trials’’ is not clear.7 In 1998, Jennings et al,16 comparing patients undergoing surgery in the years 1990 to 1991 with the years 1993 to 1994 (before and after the implementation of laparoscopy in 1992), reported that the utilization of laparoscopy was increased 14-fold for patients affected by gynecological cancer. Albeit they introduced laparoscopy in a selected population, excluding patients who needed radical pelvic surgery or complex surgical procedures, they observed an overall improvement in length of stay, without the increase of surgical-related complications.16 However, several years later, only few studies evaluated how the introduction of laparoscopic approach modified workloads and clinical practices.17,18 Although they agree in underlining the improvement of surgical-related outcomes, it is often difficult to evaluate the formal inclusion criteria for undergoing laparoscopy rather than open surgery and the degree for which laparoscopy was introduced into different clinical settings. In fact, generally, the choice to perform open abdominal versus minimally invasive treatment relies on discretion of the attending surgeons and it was not driven by specific guidelines.17 As aforementioned, in 2009, we reported how the use of laparoscopy modified our practice. We already observed a marked decrease in the need to perform open surgery and an improvement of perioperative results, although short-term term oncologic outcomes were not influenced by the introduction of minimally surgery.7 The present study supports our
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
747
International Journal of Gynecological Cancer
Bogani et al
& Volume 25, Number 4, May 2015
TABLE 5. Changes in ovarian cancer management
Age, y BMI, kg/m2 Previous abdominal surgery Charlson comorbidity index Q3 Histotype Epithelial Nonepithelial Grade (for epithelial tumor) G1 and 2 G3 FIGO stage I 9II Approach Laparoscopy Open surgery Conversions LND (PL+ PA LND) Lymph node count Positive lymph node Cysts rupture Operative time, min Estimated blood loss, mL Hospital stay, d Transfusions Intraoperative complications Postoperative complications** Readmission Adjuvant therapy (chemotherapy)
T1 (2000-2003), n = 14
T2 (2004-2007), n = 26
T3 (2008-2011), n = 41
54 (40Y82) 23.1 (18.8Y35.6) 4 (28%) 0 (0%)
56 24.2 10 2
55 21.8 14 5
(13Y76) (18Y33.7) (38%) (8%)
(20Y80) (16.6Y39.2) (34%) (12%)
P 0.75* 0.15† 0.81* 0.36*
11 (79%) 3 (21%)
24 (92%) 2 (8%)
39 (95%) 2 (5%)
0.16*
5 (45%) 6 (55%)
9 (38%) 15 (62%)
15 (38%) 24 (62%)
0.89*
10 (71%) 4 (29%)
17 (65%) 9 (35%)
22 (54%) 19 (46%)
0.41*
1 (7%) 13§ (93%) 0 14 (100%) 20 (8Y37) 1 (7%) 3 (21%) 136.3 (95Y280) 400 (100Y700) 6 (3Y11) 1 (7%) 0 (0%) 0 (0%) 1 (7%) 9 (64%)
15 (60%) 11 (40%) 0 26 (100%) 27 (8-58) 4 (15%) 1 (4%) 325 (115Y480) 300 (50Y3000) 6 (2Y30) 2 (8%) 1 (4%) 1 (4%) 0 (0%) 22 (85%)
36 (88%) 5 (12%) 2 (5%) 41 (100%) 30 (10Y59) 9 (22%) 4 (10%) 267 (105Y420) 275 (50Y1000) 4 (1-12) 1 (2%) 0 (0%) 0 (0%) 1 (2%) 38 (93%)
G0.001‡ 0.99* 90.99* 0.04|| 0.42* 0.2* G0.001¶ 0.32* 0.01# 0.57* 0.34* 0.34* 0.39* 0.03††
Data are expressed in number (%) or median (range). *No statistical differences are achieved comparing T1 vs T2, T2 vs T3, and T1 vs T3 (all P 9 0.05). †T1 vs T2, P = 0.83; T2 vs T3, P = 0.04; T1 vs T3, P = 0.69. ‡T1 vs T2, P = 0.001; T2 vs T3, P = 0.01; T1 vs T3, P G 0.001. §Two patients had diagnostic laparoscopy followed by open staging after the diagnosis of invasive ovarian cancer before we started to perform laparoscopy for ovarian cancer. ||T1 vs T2, P = 0.07; T2 vs T3, P = 0.54; T1 vs T3, P = 0.002. ¶T1 vs T2, P G 0.001; T2 vs T3, P G 0.001; T1 vs T3, P = 0.04. #T1 vs T2, P = 0.69; T2 vs T3, P = 0.01; T1 vs T3, P = 0.06. **Postoperative complications were graded per the Accordion Severity System. Only grade Q3 complications were reported.24 ††T1 vs T2, P = 0.14; T2 vs T3, P = 0.29; T1 vs T3, P = 0.009. BMI, Body mass index; FIGO, International Federation of Gynecology and Obstetrics; LND, lymphadenectomy; PA, para-aortic; PL, pelvic.
preliminary results in a larger population and it reports longterm outcomes, thus confirming the effectiveness of minimally invasive surgery. Once the operative and postoperative safety of laparoscopic approach are established, the following are the 2 main critics on its introduction into a preexisting clinical setting: (1)
748
The ‘‘steep learning curve’’ of laparoscopy with potential increase in surgical-related complication rate and longer operative time of a ‘‘new’’ technique. However, as reported by our study group7 and other authors,16Y19 the introduction of laparoscopy is not related to an increased number of complications; on the contrary, the overall complication rate * 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
International Journal of Gynecological Cancer
& Volume 25, Number 4, May 2015
Laparoscopy for Gynecological Cancers
FIGURE 1. Five-year survival outcomes. Five-year disease free (DFS) and overall survivals (OS) for endometrial, cervical, and adnexal cancers, undergoing surgery in the study period 2000 to 2003 (T1), 2004 to 2007 (T2), and 2008 to 2011 (T3). decreases.7 Similarly, operative time, after an initial increase (from T1 to T2) decreases over the study period (from T2 to T3). These figures reflect the gradual implementation of laparoscopic surgery in our practice: from simple to even more complex, technically challenging procedures over the years. (2) One might expect that the longer operative time needed to perform a procedure via laparoscopic rather than open surgery may lead to a reduction of the whole workload. However, we observed that the number of patients who presented at our unit increases dramatically over the years (from 209 in T1 to 302 in T3; approximately +50%). Three main causes could explain this as follows: first, albeit the prediction, overall operative time decreased; second, the shorter hospital stay and the lower rate of complication rate promoted a more rapid turnover of patients; and third, laparoscopy increased patients’ appealing. These latter aspects are also paramount in the perspective of a policy of cost saving. The utilization of reusable instrumentations, the minimized operative time, minimized length of stay, as well as the minimized transfusion and postoperative complication rates potentially concur in the reduced amount of money spent, over the years.26Y28 Moreover, our survival analysis showed that the embrace of laparoscopic approach does not influence oncologic outcomes. However, these results have to be interpreted with caution because groups are not homogeneous in terms of adjuvant therapy administration rate and disease characteristics. Additional limitations of this study include the inherent biases of a retrospective, single-center study design. However, the inclusion of consecutive patients with apparent organ-confined tumors reduces selection and publication biases. In fact, at the beginning of our experience, surgeons had no specific skills in laparoscopy surgery, thus supporting
the reproducibility of our results in other clinical settings. In addition, the main merit of our study is to report one of the larger series of gynecological malignancies managed with laparoscopy from a single institution. In conclusion, the present study indicates the feasibility of the gradual implementation of laparoscopic approach in the management of apparent early stage gynecological malignancies. We observed that through the introduction of laparoscopy, we can reduce the length of stay, complication, and blood transfusion rates, without neglecting medium-term outcomes, thus improving standard of care of patients affected by gynecological cancers. Further attempts are needed to reduce the rate of unnecessary open procedures, thus improving both patients’ care and workload.
REFERENCES 1. How J, Lau S, Press J, et al. Accuracy of sentinel lymph node detection following intra-operative cervical injection for endometrial cancer: a prospective study. Gynecol Oncol. 2012;127:332Y337. 2. Lavoue V, Zeng X, Lau S, et al. Impact of robotics on the outcome of elderly patients with endometrial cancer. Gynecol Oncol. 2014;133:556Y562. 3. Bogani G, Cromi A, Uccella S, et al. Nerve-sparing vs. conventional laparoscopic radical hysterectomy: a minimum 12 months follow-up study. Int J Gynecol Cancer. 2014;24:787Y793. 4. Kaushik S, Akhter K, Rufford B, et al. The use of laparostomy in patients with gynecologic cancer: first report from a UK cancer center. Int J Gynecol Cancer. 2013;23:951Y955. 5. Walker JL, Piedmonte MR, Spirtos NM, et al. Recurrence and survival after random assignment to laparoscopy versus laparotomy for comprehensive surgical staging of
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
749
Bogani et al
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
International Journal of Gynecological Cancer
uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin Oncol. 2012;30:695Y700. Wright JD, Herzog TJ, Neugut AI, et al. Comparative effectiveness of minimally invasive and abdominal radical hysterectomy for cervical cancer. Gynecol Oncol. 2012;127:11Y17. Ghezzi F, Cromi A, Uccella S, et al. Incorporating laparoscopy in the practice of a gynecologic oncology service: actual impact beyond clinical trials data. Ann Surg Oncol. 2009;16:2305Y2314. Fader AN, Seamon LG, Escobar PF, et al. Minimally invasive surgery versus laparotomy in women with high grade endometrial cancer: a multi-site study performed at high volume cancer centers. Gynecol Oncol. 2012;126:180Y185. Vaknin Z, Perri T, Lau S, et al. Outcome and quality of life in a prospective cohort of the first 100 robotic surgeries for endometrial cancer, with focus on elderly patients. Int J Gynecol Cancer. 2010;20:1367Y1373. Leitao MM Jr, Briscoe G, Santos K, et al. Introduction of a computer-based surgical platform in the surgical care of patients with newly diagnosed uterine cancer: outcomes and impact on approach. Gynecol Oncol. 2012;125:394Y399. ElSahwi KS, Hooper C, De Leon MC, et al. Comparison between 155 cases of robotic vs. 150 cases of open surgical staging for endometrial cancer. Gynecol Oncol. 2012;124:260Y264. Dowdy SC, Aletti G, Cliby WA, et al. Extra-peritoneal laparoscopic para-aortic lymphadenectomyVa prospective cohort study of 293 patients with endometrial cancer. Gynecol Oncol. 2008;111:418Y424. Bogani G, Cromi A, Uccella S, et al. Peri-operative and long-term outcomes of laparoscopic, open abdominal and vaginal surgery for endometrial cancer in patients aged 80 years or more. Int J Gynecol Cancer. 2014;24:894Y900. Ghezzi F, Cromi A, Siesto G, et al. Use of laparoscopy in older women undergoing gynecologic procedures: is it time to overcome initial concerns? Menopause. 2010;17:96Y103. Bogani G, Cromi A, Serati M, et al. Predictors of postoperative morbidity after laparoscopic versus open radical hysterectomy plus external beam radiotherapy: a propensity-matched comparison. J Surg Oncol. 2014;110:893Y898. Jennings TS, Dottino P, Rahaman J, et al. Results of selective use of operative laparoscopy in gynecologic oncology. Gynecol Oncol. 1998;70:323Y328.
750
& Volume 25, Number 4, May 2015
17. Chi DS, Abu-Rustum NR, Sonoda Y, et al. Ten-year experience with laparoscopy on a gynecologic oncology service: analysis of risk factors for complications and conversion to laparotomy. Am J Obstet Gynecol. 2004;191:1138Y1145. 18. Barakat RR, Lev G, Hummer AJ, et al. Twelve-year experience in the management of endometrial cancer: a change in surgical and postoperative radiation approaches. Gynecol Oncol. 2007;105:150Y156. 19. Fagotti A, Vizzielli G, Fanfani F, et al. Introduction of staging laparoscopy in the management of advanced epithelial ovarian, tubal and peritoneal cancer: impact on prognosis in a single institution experience. Gynecol Oncol. 2013;131:341Y346. 20. Bogani G, Cromi A, Serati M, et al. Laparoscopic and open abdominal staging for early stage ovarian cancer: our experience, systematic review and meta-analysis of comparative studies. Int J Gynecol Cancer. 2014;24:1241Y1249. 21. Bogani G, Cromi A, Uccella S, et al. Laparoscopic staging in women older than 75 years with early-stage endometrial cancer: comparison with open surgical operation. Menopause. 2014;21:945Y951. 22. Ghezzi F, Cromi A, Uccella S, et al. Transumbilical versus transvaginal retrieval of surgical specimens at laparoscopy: a randomized trial. Am J Obstet Gynecol. 2012;207:112.e1Y112.e6. 23. Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol. 2008;9:297Y303. 24. Strasberg SM, Linehan DC, Hawkins WG. The accordion severity grading system of surgical complications. Ann Surg. 2009;250:177Y186. 25. Martin RC 2nd, Brennan MF, Jaques DP. Quality of complication reporting in the surgical literature. Ann Surg. 2002;235:803Y813. 26. Dowdy SC, Borah BJ, Bakkum-Gamez JN, et al. Factors predictive of postoperative morbidity and cost in patients with endometrial cancer. Obstet Gynecol. 2012;120:1419Y1427. 27. Barnett JC, Judd JP, Wu JM, et al. Cost comparison among robotic, laparoscopic, and open hysterectomy for endometrial cancer. Obstet Gynecol. 2010;116:685Y693. 28. Lau S, Vaknin Z, Ramana-Kumar AV, et al. Outcomes and cost comparisons after introducing a robotics program for endometrial cancer surgery. Obstet Gynecol. 2012;119:717Y724.
* 2015 IGCS and ESGO
Copyright © 2015 by IGCS and ESGO. Unauthorized reproduction of this article is prohibited.
