Accepted Manuscript Laparoscopic versus Open Abdominal Management of Cervical Cancer: Long-Term Results from a Propensity-Matched Analysis Giorgio Bogani, M.D. Antonella Cromi, Ph.D Stefano Uccella, M.D. Maurizio Serati, M.D. Jvan Casarin, M.D. Ciro Pinelli, M.D. Fabio Ghezzi, M.D. PII:
S1553-4650(14)00213-1
DOI:
10.1016/j.jmig.2014.03.018
Reference:
JMIG 2284
To appear in:
The Journal of Minimally Invasive Gynecology
Received Date: 18 February 2014 Revised Date:
18 March 2014
Accepted Date: 19 March 2014
Please cite this article as: Bogani G, Cromi A, Uccella S, Serati M, Casarin J, Pinelli C, Ghezzi F, Laparoscopic versus Open Abdominal Management of Cervical Cancer: Long-Term Results from a Propensity-Matched Analysis, The Journal of Minimally Invasive Gynecology (2014), doi: 10.1016/ j.jmig.2014.03.018. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Laparoscopic versus Open Abdominal Management of Cervical Cancer: Long-Term
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Results from a Propensity-Matched Analysis
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Authors: Giorgio BOGANI, M.D.; Antonella CROMI, Ph.D; Stefano UCCELLA, M.D.;
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Maurizio SERATI, M.D.; Jvan CASARIN, M.D.; Ciro PINELLI, M.D.; Fabio GHEZZI, M.D.
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Dept. of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital, Varese,
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Italy (all authors)
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Address correspondence and reprint requests to:
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Giorgio BOGANI, M.D.
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Dept. Obstetrics and Gynecology - University of Insubria
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Piazza Biroldi, 1 - Varese, 21100, Italy
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Tel.
+39-0332-299-309
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Fax
+39-0332-299-307
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E-mail:
[email protected] 18
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Conflicts of interest:
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The Authors declare no conflicts of interest.
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No funding sources supported this investigation.
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Précis:
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Laparoscopic radical hysterectomy upholds radicality and long-term survival outcomes of
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open surgical operation, improving short-term outcomes and minimizing surgery-related
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morbidity
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ABSTRACT
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laparoscopic and open abdominal surgical management of cervical cancer.
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Design: Propensity-matched comparison of prospectively collected data.
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Design Classification: Canadian Task Force classification II-1.
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Setting: University teaching hospital.
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Patients:
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laparoscopy vs. open abdominal surgical operations for cervical cancer
propensity-matched
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Study Objective: To compare peri-operative and long-term outcomes related to
Intervention: Radical hysterectomy plus lymphadenectomy executed via laparoscopic
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(LRH) or open abdominal approach (RAH).
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Measurement and Main Results: Baseline characteristics of the study populations were
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similar. In the LRH group two (2%) patients were converted to open surgery. Patients
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undergoing LRH experienced lower blood loss (200 vs. 500 mL; p=36 months (only for non-recurrent patients), (4) presence of gross metastatic
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disease. Laparoscopic radical hysterectomy (LRH) was introduced in our department for
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primary treatment of early stage cervical cancer (stage IA2-IB1, IIA4cm, IIB) cervical cancer in 2004 and 2005 respectively. Patients with
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gross peritoneal disease (who were selected to surgical approach) underwent open
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surgery. Laparoscopic approach was offered to all patients presenting with cervical cancer,
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unless specific contraindications existed (such as documented severe cardiopulmonary
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disease). We started to perform LRH after having acquired adequate background in
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laparoscopic surgery (since 1999, 2002 and 2003 for the treatment of benign disease,
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endometrial cancer and apparent early stage ovarian cancer, respectively).
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Generally, surgical treatment included radical hysterectomy plus systematic pelvic
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lymphadenectomy; while para-aortic lymphadenectomy is limited for patients with bulky
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pelvic and/or para-aortic nodes or in case of suspicious lesions in the para-aortic area
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detected at preoperative radiological examination. LRHs were classified in accord to
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classification adopted by the Gynecological Cancer Group of the EORTC [13]. Type II and
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III radical hysterectomies were performed in accord to tumor diameter and stage of
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disease (type II radical hysterectomy was performed in patients with stage IA2 or stage
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ACCEPTED MANUSCRIPT IB1 and tumor diameter ≤ 2cm). Detailed description of our surgical technique is reported
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elsewhere [14,15].
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Patients undergoing LRH were compared to a historical cohort of patients undergoing
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open abdominal radical hysterectomy (RAH) before the incorporation of laparoscopic
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surgery (1995-2004). Since procedure was not randomly assigned to LRH or RAH group,
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we performed a propensity score analysis in order to obtain a less biased estimate of the
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effects of procedures on each outcome. Patients who underwent LRH were matched 1:1
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to patients who underwent RAH using a matching algorithm matching on the logit of the
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propensity score. Any patient undergoing LRH was matched with a patient undergoing
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RAH selected from a pool of 125 patients undergoing RAH and achieving at least 36
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months of follow-up (only for non-recurrent patients). Propensity score attempts reducing
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the bias due to confounding variables that could be found in an estimate of the treatment
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effect obtained from simply comparing outcomes among patients who had one treatment
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versus another treatment, by accounting for the covariates that predict receiving the
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treatment. Propensity score attempts to mimic a randomization process by creating a
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sample of units that received the treatment (e.g., LRH) that is comparable on all observed
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covariates to a sample of units that received another treatment (e.g., RAH).
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Over the study period, there were no significant differences in the facilities available for
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patient care and in the referral patterns of our service. Other aspects of patient
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management unrelated to surgical approach remained consistent over time. All surgical
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procedures were performed by the senior author (FG), helped by two assistants selected
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from the a team of skilled laparoscopists.
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Patients were thoroughly counseled about the different possible treatments (radiotherapy
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(± chemotherapy) vs. surgery), especially if they were diagnosed with locally-advanced
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stage of disease. Age, body mass index (BMI), comorbidity level (assessed using
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Charlson comorbidity index [16]) and disease characteristics were extracted by dedicated
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designate histologic subtypes [17]. The degree of glandular differentiation and cytologic
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atypia to determine architectural grade and stage were in accord with the International
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Federation of Obstetrics and Gynecologists (FIGO) criteria [18]. Operative times were
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recorded from the first skin incision to the last suture (skin to skin). Blood loss was
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estimated from the contents of suction devices. Hospital stay was counted from the 1st
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postoperative day. Intraoperative complications included procedural organ damage and
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events for which intravenous medications (including blood transfusions) were needed.
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Postoperative complications were graded per the Accordion Severity Score [19]. For the
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purpose of this study only grade >= 3 complications, occurred within eight weeks after
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surgery, were reported [19].
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Detailed description of adjuvant treatment and follow-up evaluation are reported elsewhere
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[15,20]. Survival data were abstracted from a dedicated database maintained by trained
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residents and prospectively up-dated on a regular basis. Rigorous efforts, including
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telephonic interviews, were done to improve quality of data reporting. Dates and sites of
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recurrence were recorded. Recurrences were classified in local (vaginal), regional
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(lymphatic pelvic and para-aortic) and distant (hematogenous, peritoneal and other
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lymphatic).
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Statistical analysis was performed with GraphPad Prism version 6.0 for Mac (GraphPad
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Software, San Diego CA) and IBM-Microsoft SPSS version 22.0 for Mac. Propensity score
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for an individual is defined as the probability of having been treated with an intervention
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based on different variables. Age, body mass index (BMI), stage (early vs. advanced),
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FIGO grade (FIGO grade 1&2 vs. 3), histotype (squamous cell vs. other), previous
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abdominal surgery (yes vs. no) and comorbidity levels were included in the model.
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Patients undergoing LRH were matched 1:1 to patients selected to a cohort of women
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undergoing RAH before the incorporation of LRH in our department, using a caliper width
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ACCEPTED MANUSCRIPT ≤0.2 standard deviations of the logit odds of the estimated propensity score. Incidence of
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events among the groups was analyzed for statistical significance by using the Fisher
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exact test. Odds ratio (OR) and 95% confidence intervals (CI) were calculated for each
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comparison. Normality testing (D’Agostino and Pearson test) was performed to determine
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whether data were sampled from a Gaussian distribution. The t–test and Mann–Whitney U
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test were used to compare continuous parametric and nonparametric variables,
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respectively. Disease-free and overall survivals, within the first 5 years after surgery, were
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estimated using the Kaplan-Meier method and compared between groups using the log-
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rank test. P values were two sided. P values less than 0.05 were considered statistically
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ACCEPTED MANUSCRIPT RESULTS
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Sixty-five propensity-matched patient pairs (130 patients) undergoing LRH vs. RAH
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represented the study group. Figure 1 shows the flow of patients thorough the study
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design. Baseline characteristics of the study populations were similar (Table 1). In the LRH
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group two patients were converted to open surgery; reason for conversions included:
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technical difficulties due to dense adhesions (n=1) in a patient with history of pelvic
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inflammatory disease and presence of gross disease (n=1) in a patient who had had
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NACT plus surgery due to the presence of locally advanced cervical cancer.
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We observed that patients undergoing LRH experienced lower blood loss (200 vs. 500 mL;
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p