A Randomized Trial of Lymphadenectomy in Patients with Advanced Ovarian Neoplasms.

BACKGROUND: Systematic pelvic and paraaortic lymphadenectomy has been widely used in the surgical treatment of patients with advanced ovarian cancer, although supporting evidence from randomized clinical trials has been limited. METHODS: We intraoperatively randomly assigned patients with newly diagnosed advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage IIB through IV) who had undergone macroscopically complete resection and had normal lymph nodes both before and during surgery to either undergo or not undergo lymphadenectomy. All centers had to qualify with regard to surgical skills before participation in the trial. The primary end point was overall survival. RESULTS: A total of 647 patients underwent randomization from December 2008 through January 2012, were assigned to undergo lymphadenectomy (323 patients) or not undergo lymphadenectomy (324), and were included in the analysis. Among patients who underwent lymphadenectomy, the median number of removed nodes was 57 (35 pelvic and 22 paraaortic nodes). The median overall survival was 69.2 months in the no-lymphadenectomy group and 65.5 months in the lymphadenectomy group (hazard ratio for death in the lymphadenectomy group, 1.06; 95% confidence interval [CI], 0.83 to 1.34; P = 0.65), and median progression-free survival was 25.5 months in both groups (hazard ratio for progression or death in the lymphadenectomy group, 1.11; 95% CI, 0.92 to 1.34; P = 0.29). Serious postoperative complications occurred more frequently in the lymphadenectomy group (e.g., incidence of repeat laparotomy, 12.4% vs. 6.5% [P = 0.01]; mortality within 60 days after surgery, 3.1% vs. 0.9% [P = 0.049]). CONCLUSIONS: Systematic pelvic and paraaortic lymphadenectomy in patients with advanced ovarian cancer who had undergone intraabdominal macroscopically complete resection and had normal lymph nodes both before and during surgery was not associated with longer overall or progression-free survival than no lymphadenectomy and was associated with a higher incidence of postoperative complications. (Funded by Deutsche Forschungsgemeinschaft and the Austrian Science Fund; LION ClinicalTrials.gov number, NCT00712218.).

The importance of the Peritoneal Cancer Index (PCI) to predict surgical outcome after neoadjuvant chemotherapy in advanced ovarian cancer.

PURPOSE: Achieving complete cytoreduction (CCR) is crucial for a patient's prognosis with advanced epithelial ovarian cancer (EOC). So far, prognostic predictors have failed to predict surgical outcome after neoadjuvant chemotherapy (NACT). In clinical trials, scores were used to predict operability in recurrent ovarian cancer (Harter et al. in N Engl J Med 385(23):2123-2131, 2021) but there is no known prediction score for CCR after NACT. The Peritoneal Cancer Index (PCI) is an established tool to predict surgical outcome in primary setting (Lampe et al. in 25:135-144, 2015). We now examined the predictive power of the PCI to achieve CCR after NACT. METHODS: In this single-center study, the data of patients with advanced stage EOC (FIGO > IIIb) treated between 01/2015 and 12/2020 were analyzed retrospectively. Inclusion criteria were a mandatory staging laparoscopy, a PCI score > 25, and NACT. CT scans were analyzed in blinded fashion according to RECIST criteria (Borgani et al. in 237; 93-99, 2019) Reaction of PCI after NACT was compared with the analysis of radiologic imaging and CA-125 levels. RESULTS: Three hundred and sixteen patients were screened, 62 were treated with NACT, and 23 were included in our analysis. 87% of cases presented with an FIGO IIIc stadium. The reduction of PCI itself after NACT showed to be the most powerful predictor for achieving CCR. The reduction of the initial PCI score by minimum of 8.5 points was a better predictor for CCR than reaching a PCI < 25. In contrast to data deriving from patients undergoing primary debulking surgery (PDS), we found a PCI of 17, rather than 25, to be a more valuable cut-off for CCR in neoadjuvant-treated patients. CONCLUSION: The extend of PCI reduction after NACT is a better predictor for achieving CCR compared with CA125 levels and radiologic imaging. The PCI must be assessed differently in neoadjuvant setting than in a primary situation. CCR was most likely for a post-NACT PCI < 17.

Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6).

BACKGROUND: The impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident. PRIMARY OBJECTIVE: Evaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence. STUDY HYPOTHESIS: Comprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65. TRIAL DESIGN: Open label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended. MAJOR INCLUSION CRITERIA: Patients with histologically confirmed endometrial cancer stages pT1b-pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible. EXCLUSION CRITERIA: Patients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease. PRIMARY ENDPOINT: Overall survival calculated from the date of randomization until death. SAMPLE SIZE: 640 patients will be enrolled in the study. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: At present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031. TRIAL REGISTRATION: NCT03438474.

Heated IntraPEritoneal Chemotherapy (HIPEC) for Patients With Recurrent Ovarian Cancer: A Systematic Literature Review.

BACKGROUND: Despite advances in surgical oncology, most patients with primary ovarian cancer develop a recurrence that is associated with a poor prognosis. The aim of this review was to establish the impact of Heated IntraPEritoneal Chemotherapy (HIPEC) in the overall survival of patients with recurrent ovarian cancer. METHODS: A search of PubMed/MEDLINE databases was performed in February 2015 using the terms "recurrent ovarian cancer," "cytoreductive surgery/cytoreduction," and "heated/hyperthermic intraperitoneal chemotherapy." Only English articles with available abstracts assessing the impact of HIPEC in patients with recurrent ovarian cancer were examined. The primary outcome measure was overall survival, whereas secondary outcomes included disease-free survival and HIPEC-related morbidity. RESULTS: Sixteen studies with 1168 patients were analyzed. Most studies were Level IV, with 4 studies graded as Level III and 1 Level II. Cisplatin was the main chemotherapeutic agent used, but variations were observed in the actual technique, temperature of perfusate, and duration of treatment. In patients undergoing cytoreductive surgery and HIPEC, the overall survival ranged between 26.7 and 35 months, with disease-free survival varying between 8.5 and 48 months. Heated IntraPEritoneal Chemotherapy seems to confer survival benefits to patients with recurrent disease, with a randomized controlled study reporting that the overall survival is doubled when cytoreductive surgery is compared with cytoreductive surgery and chemotherapy (13. 4 vs 26.7 months). Heated IntraPEritoneal Chemotherapy-related morbidity ranged between 13.6% and 100%, but it was mainly minor and not significantly different from that experienced by patients who only underwent cytoreduction. CONCLUSIONS: Cytoreductive surgery and HIPEC seem to be associated with promising results in patients with recurrent ovarian cancer. Large international prospective studies are required to further quantify the true efficacy of HIPEC and identify the optimal treatment protocol for a maximum survival benefit.

Maternal Outcome in Pregnant Women Undergoing Third Caesarean Section After Onset of Labor.

BACKGROUND/AIM: Our study compares repeat cesarian section with and without labor in progress and evaluates adverse maternal outcomes that could discourage pregnant women in planning labor at term or at least after 39 weeks of gestation as recommended due to benefits in neonatal outcome. PATIENTS AND METHODS: In this retrospective study, we analyzed 191 patients undergoing third C-section and compared two groups of women of undergoing C-section either before or after the onset of labor. The primary outcome measure was the incidence of maternal morbidity. Values of p≤0.05 were regarded as significant. RESULTS: Comparing the two subgroups, we did not find any significant differences in the occurrence of maternal complications or severe acute morbidity except for incomplete uterine rupture (p=0.04). CONCLUSION: Undergoing a third C-section after the start of labor has no relevant or adverse impact on maternal outcome. Therefore, elective repeat C-section can be planned in late weeks of gestation aiming at reducing neonatal morbidity. The higher rate of uterine dehiscence was not associated with other issues of severe acute maternal morbidity.

Pelvic Exenteration for Recurrent Vulvar Cancer: A Retrospective Study.

Pelvic exenteration (PE) is one of the most radical surgical approaches. In earlier times, PE was associated with high morbidity and mortality. Nowadays, due to improved selection of suitable patients, perioperative settings, and postoperative care, patients' outcomes have been optimized. To investigate patients' outcomes and identify possible influencing clinical and histopathological factors, we analysed 17 patients with recurrent vulvar cancer who underwent PE in our department between 2007 and 2022. The median age was 64.9 years, with a difference of 40 years between the youngest and the oldest patient (41 vs. 81 years). The mean overall survival time was 55.7 months; the longest survival time reached up to 164 months. The achievement of complete cytoreduction (p = 0.02), the indication for surgery (curative vs. palliative), and the presence of distant metastases (both p = 0.01) showed a significant impact on overall survival. The presence of lymphatic metastases (p = 0.11) seems to have an influence on overall survival (OS) time. Major complications appeared in 35% of the patients. Our results support the existing data for PE in cases of recurrent vulvar cancer; for a group of selected patients, PE is a treatment option with good overall survival times and acceptable morbidity.

Pelvic Exenteration for Recurrent Endometrial Cancer: A 15-Year Monocentric Retrospective Study.

Treatment options for recurrent endometrial adenocarcinoma are limited. In those cases, secondary surgical procedures such as pelvic exenteration form the only possible curative approach. The aim of this study was analyzing the outcomes of patients who underwent pelvic exenteration during the treatment of recurrent endometrial cancer intending to identify prognostic factors. More than 300 pelvic exenterations were performed. Fifteen patients were selected that received pelvic exenteration for recurrent endometrial adenocarcinoma. Data regarding patient characteristics, indication for surgery, complete cytoreduction, tumor grading and p53- and L1CAM-expression were collected and statistically evaluated. Univariate Cox regression was performed to identify predictive factors for long-term survival. The mean survival after pelvic exenteration for the whole patient population was 22.7 months, with the longest survival reaching up to 69 months. Overall survival was significantly longer for patients with a curative treatment intention (p = 0.015) and for patients with a well or moderately differentiated adenocarcinoma (p = 0.014). Complete cytoreduction seemed favorable with a mean survival of 32 months in contrast to 10 months when complete cytoreduction was not achieved. Pelvic exenteration is a possible treatment option for a selected group of patients resulting in a mean survival of nearly two years, offering a substantial prognostic improvement.

Ileal conduit and continent ileocecal pouch for patients undergoing pelvic exenteration: comparison of complications and quality of life.

OBJECTIVES: Creating a continent urinary pouch has become an alternative to the ileal conduit for patients undergoing exenteration for advanced gynecologic malignancies. The objective of this study was to compare clinical outcomes for the 2 methods. METHODS: In this retrospective study, we compared intraoperative and postoperative complications and quality-of-life scores for the modified ileocecal pouch and the ileal conduit in anterior or total pelvic exenteration. RESULTS: In 33 of 100 patients, an ileal pouch (IP) was created; the other 67 were treated by an ileal conduit (IC). Creating an IP prolonged the exenterative procedure by 97 minutes compared to an IC (IC, 453 minutes vs IP, 550 minutes; P = 0.009). Overall complication rates were similar, but patients with an IP had significantly more complications of urinary diversion (48%) than patients with an IC (31%; P = 0.03). Follow-up showed urinary loss and frequency of micturition to be comparable, but in patients with an IP, surgery for stomal complications (n = 2) and treatment of bladderstones were necessary more frequently (n = 3). Quality of life according to the 12-item Short Form Health Survey questionnaire was similar in both groups. CONCLUSION: A continent IP is an alternative to the IC in cases of pelvic exenteration. Early complications are more frequent with an IP than with an IC. The mode of urinary diversion has little influence on the quality of life in patients with advanced genital cancer.

Ileal conduit and continent ileocecal pouch for patients undergoing pelvic exenteration: comparison of complications and quality of life.

OBJECTIVES: Creating a continent urinary pouch has become an alternative to the ileal conduit for patients undergoing exenteration for advanced gynecologic malignancies. The objective of this study was to compare clinical outcomes for the 2 methods. METHODS: In this retrospective study, we compared intraoperative and postoperative complications and quality-of-life scores for the modified ileocecal pouch and the ileal conduit in anterior or total pelvic exenteration. RESULTS: In 33 of 100 patients, an ileal pouch (IP) was created; the other 67 were treated by an ileal conduit (IC). Creating an IP prolonged the exenterative procedure by 97 minutes compared to an IC (IC, 453 minutes vs. IP, 550 minutes; P = 0.009). Overall complication rates were similar, but patients with an IP had significantly more complications of urinary diversion (48%) than patients with an IC (31%; P = 0.03). Follow-up showed urinary loss and frequency of micturition to be comparable, but in patients with an IP, surgery for stomal complications (n = 2) and treatment of bladderstones were necessary more frequently (n = 3). Quality of life according to the 12-item Short Form Health Survey questionnaire was similar in both groups. CONCLUSION: A continent IP is an alternative to the IC in cases of pelvic exenteration. Early complications are more frequent with an IP than with an IC. The mode of urinary diversion has little influence on the quality of life in patients with advanced genital cancer.

Opportunities and Limitations of Pelvic Exenteration Surgery.

PURPOSE: The practice of exenterative surgery is sometimes controversial and has garnered a certain scepticism. Surgical studies are difficult to conduct due to insufficient data. The aim of this review is to present the current standing of pelvic exenteration from a surgical, gynaecological and urological point of view. METHODS: This review is based upon a literature review (MEDLINE (PubMed), CENTRAL (Cochrane) and EMBASE (Elsevier)) of retrospective studies on exenterative surgery from 1993-2020. Using MeSH (Medical Subject Headings) search terms, 1572 publications were found. These were evaluated and screened with respect to their eligibility using algorithms and well-defined inclusion and exclusion criteria. Therefore, the guidelines for systematic reviews (PRISMA) were used. RESULTS: A complete tumour resection (R0) often represents the only curative option for advanced pelvic carcinomas and their recurrences. A recent systematic review showed significant symptom relief in 80% of palliative patients after pelvic exenteration. Surgical limitations (distant metastases, involvement of the pelvic wall, etc.) are diminished by adequate surgical expertise and close interdisciplinary cooperation. While the mortality rate is low (2-5%), the still relatively high morbidity rate (32-84%) can be minimized by optimizing the perioperative setting. Following exenterations, roughly 79-82% of patients report satisfying results according to PROs (patient-reported outcomes). CONCLUSION: Due to multimodality treatment strategies combined with extended surgical expertise and patients' preferences, pelvic exenteration can be offered nowadays with low mortality and acceptable postoperative quality of life. The possibilities of surgical treatment are often underestimated. A multi-centre database (PelvEx Collaborative) was established to collect data and experiences to optimize the research in this field.

Intestinal complications after pelvic exenterations in gynecologic oncology.

OBJECTIVES AND METHODS: The present study reviews the frequency of intestinal complications in patients having undergone pelvic exenteration in our department between July 1999 and June 2008. RESULTS: Ninety patients with pelvic exenteration were included. R0 resection was achieved in 61 patients (67.8%), R1 in 20 patients (22.2%), and R2 in 9 patients (10.0%). Sixty-four patients had a rectal resection, all less than 7 cm from the anal verge. Forty-two of them had a rectal anastomosis; in 23 cases, with a protective colostomy. The other 22 patients had a terminal colostomy. Fifty-three patients had an ileal anastomosis for bladder reconstruction by ileal conduit, and 29 patients had an ileo-ascendostomy for an ileocecal pouch.Twenty-three patients (25.6%) needed surgical intervention for complications; anastomotic dehiscence being most frequent with 7 cases (7.8%). Three leakages appeared in ileal anastomoses (3/53, 5.7%) and 4 in rectal anastomoses (4/42, 9.5%). Although not significantly, the risk of symptomatic leakage was lower for patients with a protective colostomy (1/23, 4.3%) than for those without (3/19, 15.7%). We found no correlation between the preceding radiotherapy or chemotherapy and the frequency of breakdown of rectal anastomosis. CONCLUSIONS: The risk of intestinal complications in exenterative surgery is moderate and not higher than in surgery for rectal cancer. Clinical appearance and, hence, relevance of anastomotic leakage may be reduced by a temporary diverting stoma.

Updated Opinion of the Uterus Commission of the Gynecological Oncology Working Group (AGO) and the Gynecological Endoscopy Working Group (AGE) of the German Society of Gynecology and Obstetrics (DGGG) on the Randomized Study Comparing Minimally Invasive with Abdominal Radical Hysterectomy for Early-stage Cervical Cancer (LACC).

In this opinion on the randomized study comparing minimally invasive with abdominal radical hysterectomy for early-stage cervical cancer (LACC), the Uterus Commission of the Gynecological Oncology Working Group (AGO) and the Gynecological Endoscopy Working Group (AGE) of the Germany Society of Gynecology and Obstetrics (DGGG) state that, based on their examination of the published data, patients with FIGO stage IA1 (with LVSI), IA2 or IB1 cervical cancer must be informed about the results of this LACC study prior to making a decision on the route for radical hysterectomy.

Can clitoris-conserving surgery for early vulvar cancer improve the outcome in terms of quality of life and sexual sensation?

OBJECTIVES: Vulvar carcinomas (VC) and vulvar in situ cancers (VCIS) are rare genital malignancies. Total vulvectomy as the standard of care has been replaced by local excision during the early stages of the disease. We studied whether conservation of the clitoris in vulvar surgery has a positive effect on either the quality of life (QoL) or the sexual sensation of the patient. STUDY DESIGN: In a retrospective study, patients with and without clitoris-sparing surgery were interviewed using the Female Sexual Function Index questionnaire (FSFI) and the Short Form 12(®) questionnaire (SF-12). The frequencies of high and low levels and the medians were compared using the Cox-Mantel, Chi(2) and Fisher's exact tests. RESULTS: We identified 24 patients who had surgery in our department for VCIS or VC stage I/II, between 2006 and 2008. Ten of these patients required total inguinal lymphadenectomies and another five required sentinel node biopsies. In twelve patients, the clitoris had been spared, whereas in the remaining twelve, the clitoris had needed to be removed. These groups did not differ in terms of tumor size, stage, type of surgery or age of the patients. The evaluation of the SF-12 indicated high satisfaction in the physical scores for 33% of patients with clitoris-sparing surgery vs. 67% after clitoris resection (n.s.). For the mental domain, the rates were 58% and 67% (n.s.), respectively. In the FSFI, both groups showed comparable values <18 (n = 7) and >18 (n = 5) in sexual sensation. CONCLUSION: Reducing the surgical resection is oncologically acceptable, but improvement in the patients' quality of life or sexual sensation is not achieved solely by conserving the clitoris.