Secondary Surgical Cytoreduction Research Articles

Outcomes after recurrence of low-grade endometrial stromal sarcoma (LGESS) (150)

Objectives: To evaluate clinical characteristics of patients with recurrent low-grade endometrial sarcoma (LGESS) and identify prognostic factors associated with improved outcomes. Methods: All patients with a diagnosis of recurrent LGESS treated for their first recurrence at our institution between 1980 and 2019 were retrospectively identified. All recurrent uterine pathologies were reviewed, and pertinent clinical data were abstracted from the medical record. Survival outcomes were estimated using Kaplan-Meier method and differences in survival were analyzed using Logrank tests. Results: Among 28 patients with recurrent LGESS, the median time to first recurrence after the initial diagnosis was 49.5 months (range: 5.1-265.5). The median age at the time of recurrence was 54 years (range: 26-83). The sites of first recurrence were abdomen/pelvis (20, 71%), lung only (7, 25%), lung/spine (1, 4%). Eighteen patients (65%) had multi-site recurrent disease. The median follow-up time was 75.9 months (range: 8.3-232.7). Twenty-two patients (79%) experienced subsequent recurrence(s) with median progression-free survival (PFS) of 34.3 months (95% CI: 14.5-54.2). Median overall survival (OS) after the first recurrence was 136.2 months (95% CI: 87.4-185.0). At the time of the first recurrence, 21 patients (75%) underwent secondary surgical cytoreduction (SSR), and seven (25%) received non-surgical management alone. Reasons for non-surgical management included bony involvement (n=2), diffuse metastatic disease (n=2), short disease-free interval (DFI) (n=1), local extent of disease (n=1), and patient declining resection (n=1). Of those who underwent SSR, complete gross resection (CGR) was obtained in 15 (71%). CGR was not associated with PFS or OS, as most subsequent recurrences were salvaged. Seventeen of 21 (81%) SSR patients received postoperative therapy. ER+ and PR+ recurrent tumors and single-site recurrent disease were factors associated with a significant improvement in PFS (p=0.005 and p=0.03, respectively), but these did not impact OS (p=0.5 and p=0.2, respectively). An initial DFI of >4 years was associated with improved PFS (p=0.06) but no improvement in OS (p=0.1). Conclusions: Patients with a first recurrence of LGESS are likely to recur again. Longer DFI, ER+/PR+ tumors and single-site disease are associated with greater time to subsequent recurrence. Outcomes are generally favorable with this rare tumor, and all multi-modality therapy options should be considered for salvage, including surgical resection. Objectives: To evaluate clinical characteristics of patients with recurrent low-grade endometrial sarcoma (LGESS) and identify prognostic factors associated with improved outcomes. Methods: All patients with a diagnosis of recurrent LGESS treated for their first recurrence at our institution between 1980 and 2019 were retrospectively identified. All recurrent uterine pathologies were reviewed, and pertinent clinical data were abstracted from the medical record. Survival outcomes were estimated using Kaplan-Meier method and differences in survival were analyzed using Logrank tests. Results: Among 28 patients with recurrent LGESS, the median time to first recurrence after the initial diagnosis was 49.5 months (range: 5.1-265.5). The median age at the time of recurrence was 54 years (range: 26-83). The sites of first recurrence were abdomen/pelvis (20, 71%), lung only (7, 25%), lung/spine (1, 4%). Eighteen patients (65%) had multi-site recurrent disease. The median follow-up time was 75.9 months (range: 8.3-232.7). Twenty-two patients (79%) experienced subsequent recurrence(s) with median progression-free survival (PFS) of 34.3 months (95% CI: 14.5-54.2). Median overall survival (OS) after the first recurrence was 136.2 months (95% CI: 87.4-185.0). At the time of the first recurrence, 21 patients (75%) underwent secondary surgical cytoreduction (SSR), and seven (25%) received non-surgical management alone. Reasons for non-surgical management included bony involvement (n=2), diffuse metastatic disease (n=2), short disease-free interval (DFI) (n=1), local extent of disease (n=1), and patient declining resection (n=1). Of those who underwent SSR, complete gross resection (CGR) was obtained in 15 (71%). CGR was not associated with PFS or OS, as most subsequent recurrences were salvaged. Seventeen of 21 (81%) SSR patients received postoperative therapy. ER+ and PR+ recurrent tumors and single-site recurrent disease were factors associated with a significant improvement in PFS (p=0.005 and p=0.03, respectively), but these did not impact OS (p=0.5 and p=0.2, respectively). An initial DFI of >4 years was associated with improved PFS (p=0.06) but no improvement in OS (p=0.1). Conclusions: Patients with a first recurrence of LGESS are likely to recur again. Longer DFI, ER+/PR+ tumors and single-site disease are associated with greater time to subsequent recurrence. Outcomes are generally favorable with this rare tumor, and all multi-modality therapy options should be considered for salvage, including surgical resection.

Neoadjuvant chemotherapy with interval debulking surgery versus chemotherapy alone for advanced epithelial ovarian cancer

<h3>Objectives:</h3> The treatment of advanced epithelial ovarian cancer (EOC) involves a combination of cytoreductive surgery and chemotherapy. For patients with unresectable disease or extensive comorbidities at the time of diagnosis, administration of neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) has been shown to be a non-inferior treatment approach compared with primary cytoreduction, and has gained wider acceptance in the past decade[i],[ii]. Additionally, GOG 213 showed that in patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone[iii], The approach of chemotherapy without IDS has not been reassessed since the advent of VEG-F and PARP inhibitors and checkpoint blockade. This study aims to examine the survival outcomes of patients treated with chemotherapy alone versus those who underwent IDS. <h3>Methods:</h3> A retrospective cohort study was conducted at a single institution after IRB approval. Patients with Stage III or IV EOC diagnosed between 2005 and 2019 who received NACT due to unresectable disease or medical comorbidities were included. Patient demographics and clinical characteristics were collected. The primary outcome was the hazard of death in patients who underwent IDS (treated as a time-dependent covariate), compared to those who received chemotherapy alone. Age was categorized into groups: < 50 years, 50-64 years, and 65+ years. Kaplan-Meier curves stratified by IDS status were estimated using a landmark analysis conditional upon surviving at least 6 months post-diagnosis. <h3>Results:</h3> 81 patients met inclusion criteria, 50 (62%) received NACT + IDS, and 31 (38%) received chemotherapy alone. Four (5%) patients had <i>BRCA</i> mutations. Of the 50 patients who underwent IDS, 41 (82%) patients had an optimal debulking and 40 (80%) received additional adjuvant chemotherapy. The major surgical complication rate was 14% and the rate of upper abdominal surgery was 22%. The rate of chemotherapy toxicity was 29% in the chemotherapy alone group and 34% in the IDS group. The univariate estimate for the hazard of death in women who underwent IDS was 0.85, with a 95% CI: (.32, 2.3), p-value=.75. Adjusting for age, parity and BMI, the hazard ratio was estimated to be 1.03 with a 95% CI: (.35, 3.0), p-value=.96. There was no statistically significant difference in survival when comparing IDS status in patients who survived at least 6 months from diagnosis (p=0.45). <h3>Conclusions:</h3> While the observed hazard of death was lower in the patients who underwent IDS versus those who did not, the results were not statistically significant. While this study is underpowered to validate chemotherapy only as a treatment regimen for patients with EOC, the results warrant further large-scale investigation to assess the utility of treating advanced EOC with chemotherapy alone, particularly among the <i>BRCA</i> mutated/HRD population with chemosensitive tumors.

Laparotomy vs. minimally invasive surgery for ovarian cancer recurrence: a systematic review.

The objective of the present review is to thoroughly investigate the role of minimally invasive surgery (MIS) in the setting of secondary cytoreduction for ovarian cancer recurrence, comparing this approach to traditional open surgery. PubMed, ClinicalTrials.gov, Scopus and Web of Science databases (between 1st January 1989 and 1st January 2020), have been systematically queried to identify all articles reporting either laparoscopic or robotic-assisted secondary surgical cytoreduction for recurrent ovarian cancer. We also manually searched the reference lists of the identified studies. Only English language papers were considered. Two independent reviewers screened and identified the reports. A sub-analysis was performed including studies comparing MIS vs. open abdominal secondary cytoreduction. A total of 617 articles were considered. Among them, we included 12 retrospective studies on minimally invasive secondary cytoreduction, enrolling 372 patients (260 of whom were submitted to whether robotics or laparosopy). Three studies compared 69 patients who underwent MIS vs. 112 cases of open abdominal secondary cytoreduction. Other 9 articles described a total of 191 patients who had minimally invasive secondary cytoreduction for recurrent ovarian cancer without a comparative arm. The quality of the evidence was low. The decision regarding the use of MIS was left to surgeon's discretion; in general, the candidates to MIS were selected patients with single-site disease or few localizations of relapse. Compared to open surgery, MIS was associated with significantly lower blood loss, shorter hospital stay and less postoperative complications; the rate of complete cytoreduction to residual tumor =0 was 95.5% in MIS cases vs. 87.5% in laparotomy cases. The risk of complications was generally low. Disease-free and overall survival were comparable between groups. There is no consensus on the criteria to select patients for laparoscopic or robotic secondary cytoreduction. Intra-operative ultrasound has been proposed as a possible tool to better identify the site of recurrence and for confirmation of complete resection of disease. In conclusion, MIS is an option in selected patients with recurrent ovarian cancer, provided there is no widespread disease. Selection of patients appears of utmost importance to obtain satisfactory survival outcomes.

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

(Abstracted from N Engl J Med 2019;381:1929–1939) The National Comprehensive Cancer Network recommends secondary cytoreduction for ovarian cancer patients with recurrent disease who have received no treatment for a period of 6 months following a complete response from prior chemotherapy. Retrospective reviews and meta-analyses have shown the most benefit from this operation in those with platinum-sensitive disease and those with little or no postoperative residual disease.

Maintenance Therapy in the Treatment of Recurrent Epithelial Ovarian Cancer.

A diagnosis of recurrent epithelial ovarian cancer carries with it a very poor prognosis despite aggressive chemotherapy with or without secondary surgical cytoreduction. Recently, maintenance treatment after second-line chemotherapy has gained momentum given promising results of antiangiogenics and PARP inhibitors used in this setting. When used appropriately, these agents may provide a meaningful survival benefit with minimal effects on quality of life. This paper reveals the current literature evaluating the use of maintenance therapy in the recurrent setting for the epithelial ovarian, fallopian tube, or primary peritoneal cancers.

Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer

BackgroundSecondary surgical cytoreduction in women with platinum-sensitive, recurrent epithelial ovarian, primary peritoneal, or fallopian-tube (“ovarian”) cancer is widely practiced but has not been evaluated in phase 3 investigation.MethodsWe randomly assigned patients with recurrent ovarian cancer who had received one previous therapy, had an interval during which no platinum-based chemotherapy was used (platinum-free interval) of 6 months or more, and had investigator-determined resectable disease (to no macroscopic residual disease) to undergo secondary surgical cytoreduction and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Adjuvant chemotherapy (paclitaxel–carboplatin or gemcitabine–carboplatin) and use of bevacizumab were at the discretion of the investigator. The primary end point was overall survival.ResultsA total of 485 patients underwent randomization, 240 to secondary cytoreduction before chemotherapy and 245 to chemotherapy alone. The median follow-up was 48.1 months. Complete gross resection was achieved in 67% of the patients assigned to surgery who underwent the procedure. Platinum-based chemotherapy with bevacizumab followed by bevacizumab maintenance was administered to 84% of the patients overall and was equally distributed between the two groups. The hazard ratio for death (surgery vs. no surgery) was 1.29 (95% confidence interval [CI], 0.97 to 1.72; P=0.08), which corresponded to a median overall survival of 50.6 months and 64.7 months, respectively. Adjustment for platinum-free interval and chemotherapy choice did not alter the effect. The hazard ratio for disease progression or death (surgery vs. no surgery) was 0.82 (95% CI, 0.66 to 1.01; median progression-free survival, 18.9 months and 16.2 months, respectively). Surgical morbidity at 30 days was 9%; 1 patient (0.4%) died from postoperative complications. Patient-reported quality of life decreased significantly after surgery but did not differ significantly between the two groups after recovery.ConclusionsIn this trial involving patients with platinum-sensitive, recurrent ovarian cancer, secondary surgical cytoreduction followed by chemotherapy did not result in longer overall survival than chemotherapy alone. (Funded by the National Cancer Institute and others; GOG-0213 ClinicalTrials.gov number, NCT00565851.)

Survival and prognostic factors in patients with recurrent low-grade epithelial ovarian cancer: An analysis of five prospective phase II/III trials of NOGGO metadata base

ObjectiveLow-grade epithelial ovarian cancers (EOC), constitute the minority among all epithelial cancers. Our study objective was to focus on low-grade recurrent EOC and compare the survival with high-grade disease, as well as in regard to “platinum-sensitive” and “-resistant” recurrences according to platinum-free interval. MethodsThis is an exploratory analysis within the North-Eastern German Society of Gynecological Oncology (NOGGO) database including five randomized phase II/III trials comparing different chemotherapy regimens in recurrent EOC. We conducted survival analyses and cox-proportional regression models. ResultsOut of 1050 patients having the first recurrence, 42 (4%) patients had low-grade and 1008 (96%) patients had high-grade disease. In the subgroup of platinum-sensitive recurrences, progression-free survival (PFS) (8.7 m vs 9.7 m, p = 0.7) and overall survival (OS) (23.9 m vs 24.8 m, p = 0.9) did not differ between low-grade and high-grade diseases. In platinum-resistant recurrences, patients with low-grade ovarian cancer had significantly better PFS (7.6 m vs 3.6 m, p = 0.03) and OS (41.9 m vs 9.5 m p = 0.002) in comparison to those with high-grade cancer. At low-grade EOC, there were no significant PFS (p = 0.91) and OS (p = 0.25) differences between platinum-sensitive and –resistant recurrences. Patients with low-grade non-serous histology had lower PFS with compared to those with low-grade serous histology (p = 0.004). At cox regression analysis presence of ascites and residual disease after secondary cytoreductive surgery were independently associated with poor PFS within low-grade recurrent EOC. ConclusionOur study indicates, platinum-free interval does not have any prognostic significance at recurrent low-grade EOC and non-serous histology is associated with poorer outcome in recurrence. Secondary surgical cytoreduction to no-gross residual disease and ascites are independently associated with disease progression.

Treatment of patients with recurrent epithelial ovarian cancer for whom platinum is still an option.

Ovarian cancer remains the most deadly gynecologic cancer with the majority of patients relapsing within 3 years of diagnosis. Traditional treatment paradigms linked to platinum sensitivity or resistance are currently being questioned in the setting of new diagnostic methods and treatment options. Authors carried out review of the literature on key topics in treatment of recurrent epithelial ovarian cancer (EOC) when platinum is still an option; including secondary surgical cytoreduction, chemotherapy, novel treatment options, and maintenance therapy. A treatment algorithm is proposed. Molecular characterization of EOC is critical to help guide treatment decisions. The role of secondary cytoreductive surgery is currently being evaluated with results from Gynecologic Oncology Group (GOG) 213 and anticipated results from DESKTOP III clinical trials. Chemotherapy backbone has remained relatively unchanged but utilizing non-platinum-based regimens is under investigation. In addition, maintenance therapy with anti-angiogenic therapy and Poly (ADP-ribose) Polymerase (PARP) inhibitors has emerged as the standard of care. Novel combinations, including immunotherapy and anti-angiogenesis agents, may further change the current landscape. The treatment of recurrent EOC is rapidly changing. Clinical trial design will need to continue to evolve as many novel therapies move to the upfront setting. Ultimately, the treatment of patients with recurrent EOC must incorporate individual patient and tumor factors.

A phase III randomized controlled trial of secondary surgical cytoreduction (SSC) followed by platinum-based combination chemotherapy (PBC), with or without bevacizumab (B) in platinum-sensitive, recurrent ovarian cancer (PSOC): A NRG Oncology/Gynecologic Oncology Group (GOG) study.

5501Background: GOG-0213 is an international, open-label, randomized phase 3 trial in women with PSOC with two objectives: 1) to study the addition of B to paclitaxel/carboplatin concurrently and a...

Rezidiviertes Ovarialkarzinom: „Minimal Access Surgery“ vs. Laparotomie

Eriksson AGZ et al. Minimal access surgery compared to laparotomy for secondary surgical cytoreduction in patients with recurrent ovarian carcinoma: Perioperative and oncologic outcomes. Gynecol Oncol 2017; 146: 263 – 267

Minimal access surgery compared to laparotomy for secondary surgical cytoreduction in patients with recurrent ovarian carcinoma: Perioperative and oncologic outcomes

ObjectivesTo assess the perioperative outcomes of minimal access surgery (MAS) in secondary surgical cytoreduction (SSCR) for recurrent epithelial ovarian cancer (ROC); to compare oncologic outcomes with laparotomy (LAP). MethodsUsing an institutional database, we identified all patients with ROC undergoing SSCR from 1/5/09–6/14/14. Selection for MAS or LAP was based on surgeon preference. To minimize selection bias, preoperative imaging was reviewed for all LAP cases. In this manner, we identified potential MAS candidates, who were used in the comparison. Intent-to-treat analyses were undertaken using statistical testing. Results170 cases were identified (131 LAP, 8 LSC, 31 RBT). 68/131 (52%) LAP cases were deemed potential candidates for MAS. Feasibility analyses included 68 LAP and 39 MAS cases. Six (15%) MAS cases were converted to LAP. Median age, BMI, operative time did not differ significantly between the groups. Complete gross resection was achieved in 37/39 (95%) MAS, 63/68 (93%) LAP (P=1.0). Median estimated blood loss was 50cm3 (range, 5–500) MAS, 150cm3 (range, 0–1500) LAP (P=0.001). Median length of stay was 1day (range, 0–23) MAS, 5days (range, 1–21) LAP (P<0.001). Complications occurred in 3/39 (8%) MAS, 15/68 (22%) LAP (P=0.06). The 2-year progression-free survival was 56.1% (SE 9%) MAS, 63.5% (SE 6%) LAP (P=1.0). The 2-year overall survival was 92.2% (SE 5.4%) MAS, 81.4% (SE 5.5%) LAP (P=0.7). ConclusionsMAS for SSCR is feasible in properly selected cases. MAS is associated with favorable perioperative outcomes and similar oncologic outcomes, compared to LAP.

Bevacizumab and paclitaxel–carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial

Platinum-based chemotherapy doublets are a standard of care for women with ovarian cancer recurring 6 months after completion of initial therapy. In this study, we aimed to explore the roles of secondary surgical cytoreduction and bevacizumab in this population, and report the results of the bevacizumab component here. The multicentre, open-label, randomised phase 3 GOG-0213 trial was done in 67 predominantly academic centres in the USA (65 centres), Japan (one centre), and South Korea (one centre). Eligible patients were adult women (aged ≥18 years) with recurrent measurable or evaluable epithelial ovarian, primary peritoneal, or fallopian tube cancer, and a clinical complete response to primary platinum-based chemotherapy, who had been disease-free for at least 6 months following last infused cycle of platinum. Patients were randomly assigned (1:1) to standard chemotherapy (six 3-weekly cycles of paclitaxel [175 mg/m2 of body surface area] and carboplatin [area under the curve 5]) or the same chemotherapy regimen plus bevacizumab (15 mg/kg of bodyweight) every 3 weeks and continued as maintenance every 3 weeks until disease progression or unacceptable toxicity. Individuals who participated in both the bevacizumab objective and surgical objective (which is ongoing) were randomly assigned (1:1:1:1) to receive either of these two chemotherapy regimens with or without prior secondary cytoreductive surgery. Randomisation for the bevacizumab objective was stratified by treatment-free interval and participation in the surgical objective. The primary endpoint was overall survival, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00565851. Between Dec 10, 2007, and Aug 26, 2011, 674 women were enrolled and randomly assigned to standard chemotherapy (n=337) or chemotherapy plus bevacizumab (n=377). Median follow-up at the end of the trial on Nov 5, 2014, was 49·6 months in each treatment group (IQR 41·5-62·2 for chemotherapy plus bevacizumab; IQR 40·8-59·3 for chemotherapy), at which point 415 patients had died (214 in the chemotherapy group and 201 in the chemotherapy plus bevacizumab group). Based on pretreatment stratification data, median overall survival in the chemotherapy plus bevacizumab group was 42·2 months (95% CI 37·7-46·2) versus 37·3 months (32·6-39·7) in the chemotherapy group (hazard ratio [HR] 0·829; 95% CI 0·683-1·005; p=0·056). We identified incorrect treatment-free interval stratification data for 45 (7%) patients (equally balanced between treatment groups); a sensitivity analysis of overall survival based on the audited treatment-free interval stratification data gave an adjusted HR of 0·823 (95% CI 0·680-0·996; p=0·0447). In the safety population (all patients who initiated treatment), 317 (96%) of 325 patients in the chemotherapy plus bevacizumab group had at least one grade 3 or worse adverse event compared with 282 (86%) of 332 in the chemotherapy group; the most frequently reported of these in the chemotherapy plus bevacizumab group compared with the chemotherapy group were hypertension (39 [12%] vs two [1%]), fatigue (27 [8%] vs eight [2%]), and proteinuria (27 [8%] vs none). Two (1%) treatment-related deaths occurred in the chemotherapy group (infection [n=1] and myelodysplastic syndrome [n=1]) compared with nine (3%) in the chemotherapy plus bevacizumab group (infection [n=1], febrile neutropenia [n=1], myelodysplastic syndrome [n=1], secondary malignancy [n=1]; deaths not classified with CTCAE terms: disease progression [n=3], sudden death [n=1], and not specified [n=1]). The addition of bevacizumab to standard chemotherapy, followed by maintenance therapy until progression, improved the median overall survival in patients with platinum-sensitive recurrent ovarian cancer. Although the intention-to-treat analysis for overall survival was not significant, our sensitivity analysis based on corrected treatment-free interval stratification indicates that this strategy might be an important addition to the therapeutic armamentarium in these patients. National Cancer Institute and Genentech.

Beyond the Beyond: First Case of 9 Cytoreductive Surgeries in a Long-Surviving Ovarian Cancer Patient: Case Report

The role of surgery in recurrent ovarian cancer (ROC) is debated. Multiple prospective and retrospective series reported improved survival with optimal secondary surgical cytoreduction, but definitive results from randomized trials are needed. Up to the fourth cytoreductive surgery for recurrent disease in an attempt to improve patients' prognosis has been reported. We report the first case of multiple ROC in an Italian woman, 50 years old at diagnosis, who underwent 9 cytoreductive surgeries during her 17 years of disease with no serious postoperative complications. Multiple surgeries should not be considered as the standard treatment for ROC. In carefully selected patients, optimal cytoreductive surgery performed by highly specialized gynecologic oncologists might represent a useful tool in adjunction to chemotherapy for the management of ROC.

Predicting overall survival after secondary surgical cytoreduction for platinum-sensitive recurrent ovarian cancer: A prognostic nomogram

Objective: Patients with platinum-sensitive epithelial ovarian cancer (EOC) recurrence who undergo secondary surgical cytoreduction (SSCR) have heterogeneous outcomes. Our objective was to identify prognostic factors for overall survival (OS) to develop a nomogram that could predict OS for an individual patient undergoing SSCR.

Nomogram predicting 5-year progression-free survival after secondary surgical cytoreduction for platinum-sensitive recurrent ovarian cancer

Nomogram predicting 5-year progression-free survival after secondary surgical cytoreduction for platinum-sensitive recurrent ovarian cancer

Feasibility and perioperative outcomes of robotic-assisted surgery in the management of recurrent ovarian cancer: A multi-institutional study

ObjectivesMinimally invasive surgery for recurrent ovarian cancer is generally not performed. The aim of this study was to assess the feasibility and surgical outcomes of robotic-assisted surgery in the management of recurrent ovarian cancer. MethodsEligible patients included those with confirmed recurrent ovarian cancer amenable to surgical resection and in which a complete resection was thought to be feasible with the use of the robotic platform. Patients with evidence of carcinomatosis were not considered for a robotic approach. Clinical and pathologic data were abstracted from the medical records. Appropriate statistical tests were performed using SPSS statistical software program (SPSS 20.0 Inc., Chicago, IL). ResultsA total of 48 patients were identified. Thirty-six (75%) patients had a recurrent mass or masses isolated to one anatomic region (pelvis or abdomen). Conversion to laparotomy was necessary in 4 (8.3%) cases. In cases not requiring conversion to laparotomy, the median operative time, EBL, and length of stay were 179.5min, 50cc, and 1day, respectively. An optimal debulking was achieved in 36 (82%) cases. Complications occurred in 6 (13.6%) cases. The median operative time, EBL, length of stay, and complications were all statistically significantly lower in the cases not converted to laparotomy compared to those that were (p<0.001). ConclusionsThis study suggests that select patients with recurrent ovarian cancer in the absence of carcinomatosis may be candidates for secondary surgical cytoreduction via a robotic approach. Surgical and postoperative outcomes appear to be favorable compared to reports of laparotomy in recurrent ovarian cancer.

Secondary Cytoreduction Versus Chemotherapy Alone in the Treatment of Patients with Recurrent Ovarian Cancer: Is a Randomized Trial Worthwhile?

The review by Harter et al. [1] entitled “Surgery for relapsed ovarian cancer: when should it be offered?” appropriately analyzes major concerns related to surgery for recurrent ovarian cancer. Despite underlining published reports from various series on secondary cytoreduction in platinum-sensitive patients, seeking a satisfactory answer to the question what should be considered standard care in these patients, they present two ongoing randomized trials (AGO-OVAR DESKTOP III and GOG 213) evaluating cytoreductive surgery versus chemotherapy alone in patients with platinum-sensitive recurrent ovarian cancer. Even though we agree that these studies are needed to obtain level 1 evidence for choosing the optimal treatment in similar clinical scenarios, we feel obliged to express and draw to the scientific community’s attention certain doubts. From currently available data, no one can deny that in selected cases such as the categories identified by the inclusion criteria for the AGO-OVARDESKTOP III trial, the results obtained after secondary surgical cytoreduction in patients with recurrent ovarian cancer are better than those after chemotherapy alone [2, 3]. This consideration raises ethical and practical concerns. As physicians engaged in scientific research, it is our duty to suggest to our patients the therapeutic option likely to guarantee the best outcome. Equally important, when asking patients to take part in a randomized trial, we have the duty to inform them about the reasons for the trial and the results that the two alternative procedures proposed can guarantee. Giving correct information could presumably lead to an accrual dropout. No less important in this context are the latest developments from cytogenetic studies on ovarian carcinoma. In their critical review published on the pathogenesis of ovarian cancer, Kurman and Shih [4] divide epithelial ovarian carcinoma into two groups designated type I and type II that distinctly differ in phenotype, genotype, and clinical behavior. These new concepts on ovarian carcinogenesis inescapably imply that a “blanket approach” to the treatment of ovarian carcinoma no longer suffices. The overriding need now is to develop targeted therapies adapted to the molecular and genetic features shown by the two main tumor types. Randomized trials that fail to take these differences into account can hardly provide reliable results.

Cytoreductive surgery plus chemotherapy versus chemotherapy alone for recurrent epithelial ovarian cancer

Most women with advanced epithelial ovarian cancer will ultimately develop recurrent disease after completion of initial treatment with primary surgery and adjuvant chemotherapy. Secondary cytoreductive surgery may have survival benefits in selected patients. However, a number of chemotherapeutic agents are active in recurrent ovarian cancer and the standard treatment of patients with recurrent ovarian cancer remains poorly defined. To evaluate the effectiveness and safety of secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. We searched the Cochrane Gynaecological Cancer Group Trials Register, The Cochrane Register of Controlled Trials, (CENTRAL) Issue 1 2009, MEDLINE and EMBASE up to February 2009. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of review articles and contacted experts in the field. We searched for RCTs, quasi-randomised trials and non-randomised studies that compared secondary cytoreductive surgery and chemotherapy to chemotherapy alonein women with recurrent epithelial ovarian cancer. Three reviewers independently assessed whether potentially relevant studies met the inclusion criteria. No trials were found and therefore no data were analysed. The search strategy identified 1431 unique references of which all were excluded on the basis of title and abstract. We found no evidence from RCTs to inform decisions about secondary surgical cytoreduction and chemotherapy compared to chemotherapy alone for women with recurrent epithelial ovarian cancer. Ideally, a large randomised controlled trial or, at the very least, well designed non-randomised studies that use multivariate analysis to adjust for baseline imbalances are needed to compare these treatment modalities.

Ovarian cancer in 2010

Ovarian cancer remains responsible for the most gynecologic cancer-related deaths in women worldwide, and is the fifth leading cause of death overall [1]. The careful development of a series of randomized trials involving numerous patients, investigators and clinical trial groups encompassing many countries have led to an improvement in median overall survival from 1 year in 1975 to approximately 5 years in 2009 for optimally debulked patients with stage III disease [2–4]. This issue of Therapy reviews ongoing studies on numerous fronts that have the potential to further improve outcomes related to the prevention, diagnosis and treatment of patients with ovarian cancer. Improved cancer outcomes are associated with the need to further improve fertility preservation techniques for women with ovarian cancer. However, a recent study suggested that only 47% of oncologists refer cancer patients of childbearing age to a reproductive endo crinologist [5]. This important issue is reviewed by Herzog and colleagues [6]. They review data supporting the appropriate setting to consider fertility preservation for patients with low malignant potential, germ cell tumors and early-stage epithelial ovarian cancer. The lack of large random ized studies to direct choices in an evidence-based fashion is acknowledged, but the careful interpretation of smaller studies has allowed the development of consensus-based recommendations. In addition to the technical aspects of fertility-sparing surgery, the lack of an apparent negative effect of modern adjuvant therapy on subsequent fertility is also discussed [7]. The second part of the review addresses the emerging technology with regard to fertility preservation options. Embryo, oocyte and ovarian tissue cryo preservation allow for a wide variety of options not heretofore possible. The retrieval of oocytes also no longer requires surges in estrogen, which is important in patients with potentially estrogensensitive malignancies [8]. In addition, in vitro maturation techniques are further improving the viability of oocyte and embryo cryopreservation specimens [9]. The challenges presented here are how to integrate these technologies in a way that does not compromise cancer outcome, and this requires a careful collaboration of medical and gynecologic oncology with reproductive endocrinologists and maternal–fetal specialists. The association with improved survival and optimal primary surgical cytoreduction remains well established and recent data support the goal of complete surgical cytoreduction as having the best outcome [10]. As with many important questions in oncology, the role of secondary surgical cytoreduction is not as well defined due to a variety of factors, including patient hetero geneity, physician and patient biases, and the lack of multiple random ized prospective trials. Chi and colleagues summarize the available data supporting this approach [11]. Theoretical support is derived from older mathematical models suggesting that there is an increased rate of growth (hence chemo therapy sensitivity) in small-volume tumors, and decreasing the number of tumor cells lessens the chance for resistance-inducing mutations. The case is made that the goal of secondary surgical cyto reduction must be a complete resection if a benefit is to be achieved. The article goes on to examine selection criteria proposed to predict a successful surgical outcome (utilizing the DESKTOP I and II trials), estimates the frequency with which this can be accomplished and, finally, identifies the prognostic factors to predict prolonged survival after secondary surgical cytoreduction [12]. Most importantly, both the AGO and GOG are conducting large random ized trials addressing the value of secondary cyto reduction followed by chemo therapy versus chemo therapy only, and participation in these trials is essential to define the role of this potentially important approach for patients.

The role of secondary cytoreductive surgery for recurrent mucinous epithelial ovarian cancer (mEOC)

Background Mucinous epithelial ovarian cancer (mEOC) may exhibit a distinct biological behavior in epithelial ovarian cancer (EOC). The role of secondary cytoreductive surgery was evaluated in patients with recurrent mEOC, and the prognosis was assessed. Methods Twenty-one patients with stages IIc to IV mEOC who experienced disease recurrence and received secondary cytoreductive surgery at Fudan University Cancer Hospital between Jan. 1997 and Dec. 2005 were retrospectively reviewed. Survival curves were generated using the Kaplan–Meier method and the significant comparison of survival rate was estimated by the log-rank test. Results The median progression-free interval (PFI) was 14 months (range, 5–46 months) after the first cytoreduction. Seven patients (33%) who received secondary cytoreductive surgery were optimally cytoreduced with residual disease less than or equal 1 cm, and the other 14 patients (67%) underwent suboptimal surgical cytoreduction. The overall median survival time was 27 months (range, 8–64 months). The median survival time after recurrence was 10 months (range, 3–32 months). There was no significant statistical difference in median survival between patients with optimal and suboptimal secondary surgical cytoreduction, with an estimated survival of 10 months and 9.8 months, respectively ( P > 0.05). Conclusion Optimal primary cytoreductive surgery for advanced mEOC was very important. Once it recurs, the prognosis is very poor. Patients with recurrent mEOC should be carefully assessed before performing secondary cytoreductive surgery, as this may have limited impact on the overall survival rates.