Original Study
Oncologic Results of Retroperitoneoscopic Versus Open Surgery for T2 Upper Tract Urothelial Carcinoma Hongli Shan,1 Xiaoqing Wang,2 Qingnian Sun,3 Qihui Chen,2 Bo Xu,2 Yuanyuan Hao,2 Wei Xu1 Abstract The oncologic results of laparoscopic nephroureterectomy for pathological tumor stage T2 (pT2) upper tract urothelial carcinoma (UTUC) remain controversial. This study was designed to compare oncologic outcomes of T2 UTUC patients treated with retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy. The results showed that RNU represents a safe, minimally invasive procedure, and it produces equally beneficial oncologic results as the traditional, and more risky, open surgery procedure. Background: The present study was designed to compare oncologic outcomes of T2 upper tract urothelial carcinoma patients treated with retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy (ONU). Patients and Methods: T2 upper tract urothelial carcinoma patients were treated with RNU (n ¼ 110) or ONU (n ¼ 118) and followed-up for > 5 years. Demographic and clinical data, including preoperative indexes, intraoperative indexes, and oncological outcomes, were retrospectively compared to determine the efficacy of the 2 procedures. Results: The RNU and ONU groups were statistically similar in age, sex, tumor location, and tumor pathologic grade. The original surgery time required for RNU and ONU was statistically similar, but RNU was associated with a significantly smaller volume of intraoperative estimated blood loss and shorter length of postoperative hospital stay. Follow-up (average: 43.2 months; range, 6-72 months) revealed that the estimated 5-year overall survival rate and the estimated 5-year disease-specific survival rate after RNU was slightly worse than after ONU (66.0% vs. 67.1%, and 80.8% vs. 83.8%, respectively), and the estimated 5-year recurrence-free survival rate and the estimated 5-year intravesical recurrence-free survival rates were slightly better than ONU (79.5% vs. 77.9%, and 68.3% vs. 65.6%, respectively). However, none of these differences were statistically significant. Conclusion: The open surgery strategy and the RNU strategy are equally effective for treating T2 upper tract urothelial carcinoma. However, the RNU procedure is safer, less invasive, and requires a shorter duration of postoperative hospitalized care; thus, RNU is recommended as the preferred strategy. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2015 Elsevier Inc. All rights reserved. Keywords: Minimal invasive, Retroperitoneoscopic nephroureterectomy, Surgery strategy, Tumor relapse, T2 stage
Introduction 1
Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, Jilin, P.R. China 2 Department of Urology, General Hospital of Jinlin Oil Field, Songyuan, P.R. China 3 Department of Urology, The First Hospital of Jilin University, Changchun, Jilin, P.R. China Submitted: Mar 26, 2015; Revised: May 20, 2015; Accepted: May 29, 2015 Address for correspondence: Wei Xu, MD, Department of Clinical Laboratory, the First Hospital of Jilin University, Xinmin Street 71#, Changchun, Jilin 130021, China Fax: þ86-431-8878-2622; e-mail contact: [email protected] Address for correspondence: Xiaoqing Wang, MD, Department of Urology, the First Hospital of Jilin University, Xinmin Street 71#, Changchun, Jilin 130021, China Fax: þ86-431-8187-5807; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2015.05.011
Upper tract urothelial carcinoma (UTUC) is considered a relatively rare tumor type, and no internationally validated guidelines have been established for their treatment. Open radical nephroureterectomy (ONU) with the excision of a bladder cuff represents the gold standard of treatment for UTUC. In the first large-scale, singlesite, long-term retrospective study of UTUC, Hall et al found that surgical intervention produced 5-year disease-free survival rates of 100% for pathological tumor stage Ta (pTa), 91.7% for pT1, 72.6% for pT2, 40.5% for pT3, and 0% for pT4 tumors, respectively.1 Bladder recurrence is a common phenomenon after surgical treatment, and the recurrence rate is reported to be between
Clinical Genitourinary Cancer Month 2015
-1
Oncologic Results of Laparoscopic Surgery for T2 UTCC 15% and 40%.2-6 In 1991, Clayman et al7 reported the first laparoscopic nephroureterectomy; since then, several reports have been published that demonstrated superior short-term results and comparable oncologic outcomes with this procedure, compared with open surgery.8,9 Unfortunately, no randomized trials have been carried out to date and comparisons of the open and laparoscopic procedures are limited by differences in patient selection.10 The safety of laparoscopic nephroureterectomy has not yet been fully established,11 but the European Association of Urology has suggested that laparoscopic procedures are sufficiently effective in treating low grade and stage tumors to be approved for clinical use.12 Nephroureterectomy has been described as an excessive treatment approach for low stage UTUC, and endoscopic-based nephronsparing procedures have been suggested as a preferable alternative approach to treat Ta and T1 tumors.13,14 ONU remains the recommended method for T3 and T4 tumors.10 However, the oncologic results of laparoscopic nephroureterectomy for T2 UTUC remain controversial. Thus, we designed a retrospective analysis of 228 patients with pT2 UTUC who had undergone ONU or retroperitoneoscopic nephroureterectomy (RNU), performed by a single surgeon, to evaluate the oncologic efficacy of RNU.
Patients and Methods Clinical Data The electronic patient database of the First Hospital of Jilin University was queried for patients diagnosed with upper urinary tract carcinoma who had undergone radical nephroureterectomy and bladder cuff resection on-site. The resultant patient population was then restricted to only patients with postoperative pathologic results of pT2 stage. From January 2006 to January 2012, 228 consecutive patients with T2 UTUC were enrolled in the study. The patients were diagnosed using computed tomography (CT) urography, intravenous urography, retrograde pyelography, or ureteroscopy with or without biopsy. Preoperative cystoscopy and radiologic examinations were performed to rule out metastasis and concomitant bladder cancer. Before surgical treatment, each patient had been comprehensively informed of the particular advantages of ONU and RNU, and the related complications of each. The type of surgery was selected by the patient. The patients whose clinincal tumor (cT) stage was cT2 received a regional lymph node dissection. The bladder cuff resection for all of the patients who underwent ONU was performed with an open surgery. In the RNU group, the bladder cuff resection was performed via an endourologic approach or open surgery. The transurethral resection of the ureteral orifice was performed before the RNU, and the ureter was not clipped distally during the whole procedure. The Foley catheter was removed at 4 to 5 days after the surgery. For patients who received an endourological approach, a cystogram was not needed to be performed before the removal of the Foley catheter. All patients received a single dose of intravesical mitomycin C within the first 3 days after the surgery to prevent bladder recurrence. The patients who had a lymph node metastasis received postoperative chemotherapy.
Follow-Up
2
-
Follow-up was carried out once every 3 months for the first 3 years, then every 6 months for the following 2 years, and annually
Clinical Genitourinary Cancer Month 2015
thereafter. Follow-up consisted of taking of a history, physical examination, hematocrit measurement, serum creatinine measurement, urinary cytology, chest radiograph, cystoscopic evaluation of the bladder, and CT scan of the abdomen and pelvis. A bone scan, chest CT scan, and magnetic resonance imaging were performed, if necessary. Disease recurrence was defined as local recurrence, intravesical recurrence, and distant metastasis.
Statistical Analysis SPSS software (version 10.0; SPSS Institute, Chicago, IL) was used for all statistical analysis. A Student t test or the ManneWhitney test was used to compare continuous variables, and the c2 test was used to compare categorical variables. Recurrence was evaluated from the date of surgery. The KaplaneMeier method was used to calculate survival rates. Tumor recurrence-free survival was defined as the interval from surgery to the first appearance of local, intravesical recurrence, distant metastasis, or to the end of the study, whichever came first. For all statistical tests, P < .05 was considered to indicate a significant difference.
Results There were no significant differences in age, sex, tumor location, or tumor pathologic grade between the 2 groups. The average surgery time was statistically similar between the 2 groups (P ¼ .12). The intraoperative estimated blood loss in the RNU group showed a significant advantage (220.2 81.9 mL vs. 299.5 118.2 mL; P < .001). In addition, the time until the first meal (in hours) and postoperative hospital stay (in days) were significantly shorter in the RNU group (28.9 8.6 hours vs. 39.6 9.7 hours and 5.6 2.1 days vs. 7.6 2.8 days, respectively; P < .001). The intraoperative complications included bleeding, peritoneal and pleural injury, and spleen injury. Fever, incision infection, deep vein thrombosis, and lymphatic fistula were the major postoperative complications. The distribution of complications according to the Clavien grading system was similar in the 2 groups (P ¼ .45; Table 1). The median follow-up time was 43.2 months (range, 6-72 months). In the RNU group, 17 (15.5%) patients died of UTUC and 19 (17.3%) patients died of other disease. The estimated 5-year overall survival rate was 66.0% and the estimated 5-year diseasespecific survival rate was 80.8%. In the ONU group, 19 (16.1%) patients died of UTUC and 16 (13.6%) patients died from other causes. The ONU estimated 5-year overall survival rate was 67.1% and the disease-specific survival rate was 83.8%. Neither of the survival rates was statistically different between the 2 groups (Figures 1 and 2). The patients who had a lymph node metastasis died during the follow-up time. There are 2 types of UTUC tumor recurrence: intravesical and local. No distant metastasis occurred before local recurrence. Of all patients, 32.5% experienced any type of recurrence and 4 patients experienced both types of recurrence. Intravesical recurrence occurred in 48 (21.1%) (RNU, n ¼ 22; ONU, n ¼ 26) and local recurrence occurred in 26 (11.4%) (RNU, n ¼ 12; ONU, n ¼ 14). The estimated 5-year recurrence-free survival rate in the RNU group was 68.3%, and 65.6% in the ONU group; the recurrence-free probabilities were similar between the 2 groups (Figure 3). The estimated 5-year intravesical recurrence-free
Hongli Shan et al Table 1 Patient Characteristics Variable Mean Age (Range), Years
RNU (n [ 110)
ONU (n [ 118)
P
67.9 (50-81)
67.7 (32-87)
.42
Sex, n (%)
.59
Male
68 (61.8)
77 (65.3)
Female
42 (38.2)
41 (37.7)
Renal pelvis
67 (60.9)
74 (62.7)
Ureter
43 (41.9)
44 (37.3)
Upper
18 (41.9)
21 (47.7)
Middle
9 (20.9)
10 (22.7)
Lower
16 (37.2)
13 (29.6)
Yes
9 (8.2)
11 (9.3)
No
101 (91.8)
107 (90.7)
Tumor Location, n (%)
.79
Previous Bladder Tumor, n (%)
.76
cT Stage, n (%) 1
12 (10.9)
9 (7.6)
2
77 (70.0)
85 (72.0)
3
21 (19.1)
24 (20.4)
0
107 (97.3)
113 (95.8)
1
3 (2.7)
5 (4.2)
1
40 (36.4)
48 (40.7)
2
56 (50.9)
58 (49.2)
3
14 (12.7)
12 (10.1)
.74
pN Stage, n (%)
.54
Grade, n (%)
.73
Oncologic Results of Retroperitoneoscopic Versus Open Surgery for T2 Upper Tract Urothelial Carcinoma Hongli Shan,1 Xiaoqing Wang,2 Qingnian Sun,3 Qihui Chen,2 Bo Xu,2 Yuanyuan Hao,2 Wei Xu1 Abstract The oncologic results of laparoscopic nephroureterectomy for pathological tumor stage T2 (pT2) upper tract urothelial carcinoma (UTUC) remain controversial. This study was designed to compare oncologic outcomes of T2 UTUC patients treated with retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy. The results showed that RNU represents a safe, minimally invasive procedure, and it produces equally beneficial oncologic results as the traditional, and more risky, open surgery procedure. Background: The present study was designed to compare oncologic outcomes of T2 upper tract urothelial carcinoma patients treated with retroperitoneoscopic nephroureterectomy (RNU) or open radical nephroureterectomy (ONU). Patients and Methods: T2 upper tract urothelial carcinoma patients were treated with RNU (n ¼ 110) or ONU (n ¼ 118) and followed-up for > 5 years. Demographic and clinical data, including preoperative indexes, intraoperative indexes, and oncological outcomes, were retrospectively compared to determine the efficacy of the 2 procedures. Results: The RNU and ONU groups were statistically similar in age, sex, tumor location, and tumor pathologic grade. The original surgery time required for RNU and ONU was statistically similar, but RNU was associated with a significantly smaller volume of intraoperative estimated blood loss and shorter length of postoperative hospital stay. Follow-up (average: 43.2 months; range, 6-72 months) revealed that the estimated 5-year overall survival rate and the estimated 5-year disease-specific survival rate after RNU was slightly worse than after ONU (66.0% vs. 67.1%, and 80.8% vs. 83.8%, respectively), and the estimated 5-year recurrence-free survival rate and the estimated 5-year intravesical recurrence-free survival rates were slightly better than ONU (79.5% vs. 77.9%, and 68.3% vs. 65.6%, respectively). However, none of these differences were statistically significant. Conclusion: The open surgery strategy and the RNU strategy are equally effective for treating T2 upper tract urothelial carcinoma. However, the RNU procedure is safer, less invasive, and requires a shorter duration of postoperative hospitalized care; thus, RNU is recommended as the preferred strategy. Clinical Genitourinary Cancer, Vol. -, No. -, --- ª 2015 Elsevier Inc. All rights reserved. Keywords: Minimal invasive, Retroperitoneoscopic nephroureterectomy, Surgery strategy, Tumor relapse, T2 stage
Introduction 1
Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, Jilin, P.R. China 2 Department of Urology, General Hospital of Jinlin Oil Field, Songyuan, P.R. China 3 Department of Urology, The First Hospital of Jilin University, Changchun, Jilin, P.R. China Submitted: Mar 26, 2015; Revised: May 20, 2015; Accepted: May 29, 2015 Address for correspondence: Wei Xu, MD, Department of Clinical Laboratory, the First Hospital of Jilin University, Xinmin Street 71#, Changchun, Jilin 130021, China Fax: þ86-431-8878-2622; e-mail contact: [email protected] Address for correspondence: Xiaoqing Wang, MD, Department of Urology, the First Hospital of Jilin University, Xinmin Street 71#, Changchun, Jilin 130021, China Fax: þ86-431-8187-5807; e-mail contact: [email protected]
1558-7673/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clgc.2015.05.011
Upper tract urothelial carcinoma (UTUC) is considered a relatively rare tumor type, and no internationally validated guidelines have been established for their treatment. Open radical nephroureterectomy (ONU) with the excision of a bladder cuff represents the gold standard of treatment for UTUC. In the first large-scale, singlesite, long-term retrospective study of UTUC, Hall et al found that surgical intervention produced 5-year disease-free survival rates of 100% for pathological tumor stage Ta (pTa), 91.7% for pT1, 72.6% for pT2, 40.5% for pT3, and 0% for pT4 tumors, respectively.1 Bladder recurrence is a common phenomenon after surgical treatment, and the recurrence rate is reported to be between
Clinical Genitourinary Cancer Month 2015
-1
Oncologic Results of Laparoscopic Surgery for T2 UTCC 15% and 40%.2-6 In 1991, Clayman et al7 reported the first laparoscopic nephroureterectomy; since then, several reports have been published that demonstrated superior short-term results and comparable oncologic outcomes with this procedure, compared with open surgery.8,9 Unfortunately, no randomized trials have been carried out to date and comparisons of the open and laparoscopic procedures are limited by differences in patient selection.10 The safety of laparoscopic nephroureterectomy has not yet been fully established,11 but the European Association of Urology has suggested that laparoscopic procedures are sufficiently effective in treating low grade and stage tumors to be approved for clinical use.12 Nephroureterectomy has been described as an excessive treatment approach for low stage UTUC, and endoscopic-based nephronsparing procedures have been suggested as a preferable alternative approach to treat Ta and T1 tumors.13,14 ONU remains the recommended method for T3 and T4 tumors.10 However, the oncologic results of laparoscopic nephroureterectomy for T2 UTUC remain controversial. Thus, we designed a retrospective analysis of 228 patients with pT2 UTUC who had undergone ONU or retroperitoneoscopic nephroureterectomy (RNU), performed by a single surgeon, to evaluate the oncologic efficacy of RNU.
Patients and Methods Clinical Data The electronic patient database of the First Hospital of Jilin University was queried for patients diagnosed with upper urinary tract carcinoma who had undergone radical nephroureterectomy and bladder cuff resection on-site. The resultant patient population was then restricted to only patients with postoperative pathologic results of pT2 stage. From January 2006 to January 2012, 228 consecutive patients with T2 UTUC were enrolled in the study. The patients were diagnosed using computed tomography (CT) urography, intravenous urography, retrograde pyelography, or ureteroscopy with or without biopsy. Preoperative cystoscopy and radiologic examinations were performed to rule out metastasis and concomitant bladder cancer. Before surgical treatment, each patient had been comprehensively informed of the particular advantages of ONU and RNU, and the related complications of each. The type of surgery was selected by the patient. The patients whose clinincal tumor (cT) stage was cT2 received a regional lymph node dissection. The bladder cuff resection for all of the patients who underwent ONU was performed with an open surgery. In the RNU group, the bladder cuff resection was performed via an endourologic approach or open surgery. The transurethral resection of the ureteral orifice was performed before the RNU, and the ureter was not clipped distally during the whole procedure. The Foley catheter was removed at 4 to 5 days after the surgery. For patients who received an endourological approach, a cystogram was not needed to be performed before the removal of the Foley catheter. All patients received a single dose of intravesical mitomycin C within the first 3 days after the surgery to prevent bladder recurrence. The patients who had a lymph node metastasis received postoperative chemotherapy.
Follow-Up
2
-
Follow-up was carried out once every 3 months for the first 3 years, then every 6 months for the following 2 years, and annually
Clinical Genitourinary Cancer Month 2015
thereafter. Follow-up consisted of taking of a history, physical examination, hematocrit measurement, serum creatinine measurement, urinary cytology, chest radiograph, cystoscopic evaluation of the bladder, and CT scan of the abdomen and pelvis. A bone scan, chest CT scan, and magnetic resonance imaging were performed, if necessary. Disease recurrence was defined as local recurrence, intravesical recurrence, and distant metastasis.
Statistical Analysis SPSS software (version 10.0; SPSS Institute, Chicago, IL) was used for all statistical analysis. A Student t test or the ManneWhitney test was used to compare continuous variables, and the c2 test was used to compare categorical variables. Recurrence was evaluated from the date of surgery. The KaplaneMeier method was used to calculate survival rates. Tumor recurrence-free survival was defined as the interval from surgery to the first appearance of local, intravesical recurrence, distant metastasis, or to the end of the study, whichever came first. For all statistical tests, P < .05 was considered to indicate a significant difference.
Results There were no significant differences in age, sex, tumor location, or tumor pathologic grade between the 2 groups. The average surgery time was statistically similar between the 2 groups (P ¼ .12). The intraoperative estimated blood loss in the RNU group showed a significant advantage (220.2 81.9 mL vs. 299.5 118.2 mL; P < .001). In addition, the time until the first meal (in hours) and postoperative hospital stay (in days) were significantly shorter in the RNU group (28.9 8.6 hours vs. 39.6 9.7 hours and 5.6 2.1 days vs. 7.6 2.8 days, respectively; P < .001). The intraoperative complications included bleeding, peritoneal and pleural injury, and spleen injury. Fever, incision infection, deep vein thrombosis, and lymphatic fistula were the major postoperative complications. The distribution of complications according to the Clavien grading system was similar in the 2 groups (P ¼ .45; Table 1). The median follow-up time was 43.2 months (range, 6-72 months). In the RNU group, 17 (15.5%) patients died of UTUC and 19 (17.3%) patients died of other disease. The estimated 5-year overall survival rate was 66.0% and the estimated 5-year diseasespecific survival rate was 80.8%. In the ONU group, 19 (16.1%) patients died of UTUC and 16 (13.6%) patients died from other causes. The ONU estimated 5-year overall survival rate was 67.1% and the disease-specific survival rate was 83.8%. Neither of the survival rates was statistically different between the 2 groups (Figures 1 and 2). The patients who had a lymph node metastasis died during the follow-up time. There are 2 types of UTUC tumor recurrence: intravesical and local. No distant metastasis occurred before local recurrence. Of all patients, 32.5% experienced any type of recurrence and 4 patients experienced both types of recurrence. Intravesical recurrence occurred in 48 (21.1%) (RNU, n ¼ 22; ONU, n ¼ 26) and local recurrence occurred in 26 (11.4%) (RNU, n ¼ 12; ONU, n ¼ 14). The estimated 5-year recurrence-free survival rate in the RNU group was 68.3%, and 65.6% in the ONU group; the recurrence-free probabilities were similar between the 2 groups (Figure 3). The estimated 5-year intravesical recurrence-free
Hongli Shan et al Table 1 Patient Characteristics Variable Mean Age (Range), Years
RNU (n [ 110)
ONU (n [ 118)
P
67.9 (50-81)
67.7 (32-87)
.42
Sex, n (%)
.59
Male
68 (61.8)
77 (65.3)
Female
42 (38.2)
41 (37.7)
Renal pelvis
67 (60.9)
74 (62.7)
Ureter
43 (41.9)
44 (37.3)
Upper
18 (41.9)
21 (47.7)
Middle
9 (20.9)
10 (22.7)
Lower
16 (37.2)
13 (29.6)
Yes
9 (8.2)
11 (9.3)
No
101 (91.8)
107 (90.7)
Tumor Location, n (%)
.79
Previous Bladder Tumor, n (%)
.76
cT Stage, n (%) 1
12 (10.9)
9 (7.6)
2
77 (70.0)
85 (72.0)
3
21 (19.1)
24 (20.4)
0
107 (97.3)
113 (95.8)
1
3 (2.7)
5 (4.2)
1
40 (36.4)
48 (40.7)
2
56 (50.9)
58 (49.2)
3
14 (12.7)
12 (10.1)
.74
pN Stage, n (%)
.54
Grade, n (%)
.73
