To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer.
The Society of Gynecologic ...Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature.
Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are noninferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality.
All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
Abstract Objective To review the current evidence on the effects of intra-abdominal morcellation on survival outcomes of patients affected by unexpected uterine leiomyosarcoma (ULMS) and to estimate ...the risk of recurrence in those patients. Methods PubMed (MEDLINE), Scopus, Embase, Web of Science databases as well as ClinicalTrails.gov, were searched for data evaluating the effects of intra-abdominal morcellation on survival outcomes of patients with undiagnosed ULMS. Studies were evaluated per the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) and the American College of Obstetricians and Gynecologists (ACOG) guidelines. Results Sixty manuscripts were screened, 11 (18%) were selected and four (7%) were included. Overall, 202 patients were included: 75 (37%) patients had morcellation of ULMS, while 127 (63%) patients had not. A meta-analysis of these studies showed that morcellation increased the overall (62% vs. 39%; OR: 3.16 (95% CI: 1.38, 7.26)) and intra-abdominal (39% vs. 9%; OR: 4.11 (95% CI: 1.92, 8.81)) recurrence rates as well as death rate (48% vs. 29%; OR: 2.42 (95% CI: 1.19, 4.92)). No between-group difference in cumulative extra-abdominal recurrence (OR: 0.34 (95% CI: 0.07, 1.59)) rate was observed. Conclusions Our data support a significant correlation between uterine morcellation and an increased risk of intra-abdominal recurrence in patients affected by unexpected ULMS. However, the limited data on this issue and the absence of high level of evidence suggest the need of further studies designed to estimate the risk to benefit ratio of morcellation in patients with uterine fibroids and undiagnosed ULMS.
Abstract Purpose To provide guidance to clinicians regarding the use of neoadjuvant chemotherapy and interval cytoreduction among women with stage IIIC or IV epithelial ovarian cancer. Methods The ...Society of Gynecologic Oncology and the American Society of Clinical Oncology convened an Expert Panel and conducted a systematic review of the literature. Results Four phase III clinical trials form the primary evidence base for the recommendations. The published studies suggest that for selected women with stage IIIC or IV epithelial ovarian cancer, neoadjuvant chemotherapy and interval cytoreduction are non-inferior to primary cytoreduction and adjuvant chemotherapy with respect to overall and progression-free survival and are associated with less perioperative morbidity and mortality. Recommendations All women with suspected stage IIIC or IV invasive epithelial ovarian cancer should be evaluated by a gynecologic oncologist prior to initiation of therapy. The primary clinical evaluation should include a CT of the abdomen and pelvis, and chest imaging (CT preferred). Women with a high perioperative risk profile or a low likelihood of achieving cytoreduction to < 1 cm of residual disease (ideally to no visible disease) should receive neoadjuvant chemotherapy. Women who are fit for primary cytoreductive surgery, and with potentially resectable disease, may receive either neoadjuvant chemotherapy or primary cytoreductive surgery. However, primary cytoreductive surgery is preferred if there is a high likelihood of achieving cytoreduction to < 1 cm (ideally to no visible disease) with acceptable morbidity. Before neoadjuvant chemotherapy is delivered, all patients should have confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer. Additional information is available at www.asco.org/NACT-ovarian-guideline and www.asco.org/guidelineswiki.
Mesenchymal (MES) subtype of high-grade serous ovarian cancer (HGSOC) is associated with worse outcomes including survival and resectability compared with other molecular subtypes. Molecular subtypes ...have historically been derived from ‘tumor’, consisting of both cancer and stromal cells. We sought to determine the origins of multiple MES subtype gene signatures in HGSOC.
Fifteen patients with MES subtype of HGSOC diagnosed between 2010 and 2013 were identified. Formalin-fixed paraffin-embedded (FFPE) blocks from primary surgery were sectioned for immunohistochemistry (IHC) staining of relevant proteins. Eight genes (ACTA2, COL5A1, COL11A1, FAP, POSTN, VCAN, ZEB1 and p-SMAD2) were selected for IHC staining based on their differential expression in MES vs. non-MES subtypes of HGSOC. Slides were scored for intensity and localization and simple statistics were used to compare expression results in cancer vs. stroma and between primary and metastatic sites.
COL5A1, VCAN, FAP, and ZEB1 proteins were almost exclusively expressed by stroma as opposed to cancer cells. In addition, stromal expression was dominant for ACTA2, COL11A1, POSTN and p-SMAD2. In general there were minimal differences in expression of proteins between primary and metastatic sites, exceptions being COL5A1 (reduced in metastases) and COL11A1 (increased in metastases). Nuclear p-SMAD2 expression was more common in metastatic stroma.
The existing molecular classification of HGSOC MES subtype reflects a significant stromal contribution, suggesting an important role in HGSOC behavior and thus stroma may be a relevant therapeutic target. Specific patterns of expression indicate that collagens and TGF-β signaling are involved in the metastatic process.
•Stroma significantly contributes to the molecular classification of MES subtype of HGSOC.•Collagen expression is associated with metastases of MES subtype of HGSOC but with different roles.•Activated TGF-β signaling is associated with metastases of MES subtype of HGSOC.
Background Advanced ovarian cancer (OC) is associated with impaired performance status and comorbidities for many patients. These factors have an impact on the decision to perform extended surgical ...cytoreduction. However, the trade-off between short-term morbidity and overall survival is complex, and few data are available analyzing the combined effects of these variables. Purpose The purpose of the study was to evaluate the impact of patients’ age and American Society of Anesthesiologists (ASA) and surgical complexity score (SCS) on short-term morbidity and overall survival. Study Design Presurgical patient characteristics, surgical procedures performed, and outcomes were assessed in a cohort of consecutive primary OC patients. An SCS from 1 to 3 was developed to adjust for the extent of surgery (simple to complex, respectively). Primary outcomes were 30 day major morbidity (sepsis, thromboembolic, cardiac, or reoperation), 3 month mortality, and overall survival (OS). Results Two hundred nineteen consecutive patients with stage IIIC-IV OC were included. We observed a correlation between ASA and both short-term morbidity ( P = .006) and 3 month mortality ( P = .006). Age was independently associated with both short-term morbidity ( P = .010) and 3 month mortality ( P = .005). SCS correlated directly with morbidity ( P < .001) but was not correlated with mortality ( P = .266). The independent predictors of morbidity (ASA, age, and SCS) were used to develop risk prediction categories: risk of expected complications ranged from 2.5% to 67.6%, depending on category. Despite the increased risk of complications, however, more complex surgery carried a survival benefit in all the risk groups, owing to the observation that residual disease (RD) and SCS held a prognostic significance independent of age and ASA ( P < .001 and P = .001, respectively). Conclusion Because of the survival benefit from lower RD, a less aggressive surgical effort results in poorer OS. However, the risk of complications are substantial for complex surgeries in the highest-risk patients: risk stratification should be used to help plan perioperative care and consider optimal treatment planning.
The aim of the present review is to summarize the current evidence on the role of pelvic and para‐aortic lymphadenectomy in endometrial cancer. In 1988, the International Federation of Obstetrics and ...Gynecology recommended surgical staging for endometrial cancer patients. However, 25 years later, the role of lymph node dissection remains controversial. Although the findings of two large independent randomized trials suggested that pelvic lymphadenectomy provides only adjunctive morbidity with no clear influence on survival outcomes, the studies have many pitfalls that limit interpretation of the results. Theoretically, lymphadenectomy may help identify patients with metastatic dissemination, who may benefit from adjuvant therapy, thus reducing radiation‐related morbidity. Also, lymphadenectomy may eradicate metastatic disease. Because lymphatic spread is relatively uncommon, our main effort should be directed at identifying patients who may potentially benefit from lymph node dissection, thus reducing the rate of unnecessary treatment and associated morbidity. This review will discuss the role of lymphadenectomy in endometrial cancer, focusing on patient selection, extension of the surgical procedure, postoperative outcomes, quality of life and costs. The need for new surgical studies and efficacious systemic drugs is recommended.
The relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care and survival outcome are unclear.
A population-based analysis of National ...Cancer Data Base (NCDB) records for invasive primary epithelial ovarian cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis.
A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio HR = 1.43, 95% confidence interval CI = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio OR = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11).
These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.
Abstract Objective To prospectively assess pelvic and para-aortic lymph node metastases in endometrial cancer with lymphatic dissemination, emphasizing the examination of para-aortic metastases ...relative to the inferior mesenteric artery (IMA). Methods Over 36 months, 422 consecutive patients were managed by predefined surgical guidelines differentiating low-risk patients from patients at risk for dissemination requiring systematic lymphadenectomy. Low risk was defined as grade 1 or 2 endometrioid type with myometrial invasion (MI) ≤ 50% and primary tumor diameter (PTD) ≤ 2 cm. Pelvic and para-aortic lymph nodes were submitted separately, with nodes identified from all 8 pelvic and 4 para-aortic node-bearing basins. Surgical quality assessments examined median node counts (primary surrogate for quality) and nodes harvested above and below the IMA and excised gonadal veins (secondary surrogates). Results Lymphadenectomy was not required in 27% of patients (all low risk) and in 33% ( n = 112) of endometrioid cases. However, 22 patients (20%) of this latter cohort had lymphadenectomy and all lymph nodes were negative. Sixty-three (22%) of 281 patients undergoing lymphadenectomy had lymph node metastases: both pelvic and para-aortic in 51%, only pelvic in 33%, and isolated to the para-aortic area in 16%. Therefore, 67% of patients with lymphatic dissemination had para-aortic lymph node metastases. Furthermore, 77% of patients with para-aortic node involvement had metastases above the IMA, whereas nodes in the ipsilateral para-aortic area below the IMA and ipsilateral common iliac basin were declared negative in 60% and 71%, respectively. Gonadal veins were excised in 25 patients with para-aortic node metastases; 7 patients (28%) had documented metastatic involvement of gonadal veins or surrounding soft tissue. Conclusions The high rate of lymphatic metastasis above the IMA indicates the need for systematic pelvic and para-aortic lymphadenectomy (vs sampling) up to the renal vessels. The latter should include consideration of excision of the gonadal veins. Conversely, lymphadenectomy does not benefit patients with grade 1 and 2 endometrioid lesions with MI ≤ 50% and PTD ≤ 2 cm.
Abstract Objective To: a) identify prognostic factors in patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy (NACT) and interval debulking surgery (IDS), and b) compare ...post-surgical survival between patients treated with NACT/IDS for presumed unresectable disease and stage IIIC/IV patients who underwent suboptimal primary debulking surgery (PDS). Methods This was a retrospective study of consecutive stage IIIC or IV patients undergoing IDS after NACT at Mayo Clinic from January 2007 to December 2013. A subset of patients receiving NACT/IDS for the indication of unresectable disease were matched 1:1 on age and stage to a cohort of patients who underwent suboptimal PDS between 2003 and 2011. Hazard ratios and corresponding 95% confidence intervals were estimated from Cox proportional hazards models. Results We identified 87 patients treated with NACT/IDS: the median OS and PFS following surgery was 2.4 and 1.0 years, respectively. Factors associated with significantly worse OS were older age (adjusted HR 1.60 per 10-year increase in age, 95% CI 1.18, 2.16) and elevated CA-125 before IDS (adjusted HR 2.30 for CA-125 > 35 U/mL, 95% CI 1.25, 4.23). Number of adjuvant chemotherapy cycles administered did not have a significant effect on survival. In the matched cohort analysis of presumed unresectable cases undergoing NACT/IDS vs suboptimal PDS cases (n = 45 each), the NACT/IDS group had a significant OS advantage (HR 0.53; 95% CI 0.32, 0.88), and fewer patients experienced a 30-day postoperative Accordion grade 3/4 complication (11% vs 36%, P = 0.01). Conclusions Younger age and normalization of CA-125 prior to IDS are associated with improved survival with NACT/IDS. For primary EOC where resection to residual disease of 1 cm or less is unlikely, NACT/IDS is associated with improved survival and reduced perioperative morbidity compared to PDS. As these patients are likely best served by NACT/IDS, more reliable predictors of resectability would be valuable.
Abstract Objective To examine the effect of hospital procedure volume and other prognostic variables on overall survival outcome and likelihood of receiving standard recommended care among patients ...with advanced-stage epithelial ovarian cancer. Methods The National Cancer Data Base (NCDB) was searched for patients undergoing primary treatment for FIGO Stage IIIC/IV epithelial ovarian cancer from 1996 to 2005. The average annual surgical procedure volume was derived for each reporting hospital. Quartile ranking discriminated four groups of hospitals based on annual surgical volume: low (< 9), intermediate (9–20), high (21–35), and very high (> 35). Cox proportional hazards modeling was used to determine the impact on overall survival of hospital surgical volume adjusted for treatment, FIGO/AJCC stage, ethnicity, age, payer status, household income, and tumor grade. Binomial multivariate logistic regression modeling was used to assess differences in patient demographic, tumor, and treatment variables between high/very high volume hospitals and low/intermediate volume hospitals. Results A total of 45,929 patients were identified. After adjusting for other factors, overall survival was significantly correlated with hospital case volume: very high (reference); high (HR 0.98, 95% CI = 0.92–1.04); intermediate (HR 1.08, 95% CI = 1.01–1.15); and low (HR 1.14, 95% CI = 1.07–1.22). Compared to low and intermediate volume hospitals, patients treated at very high and high-volume hospitals were less likely to receive neo-adjuvant chemotherapy (OR = 0.33, 95% CI = 1.18–1.50) or surgery alone (OR = 0.77, 95% CI = 0.73–0.82) instead of initial surgery and adjuvant chemotherapy. Conclusions Hospital ovarian cancer surgical volume ≥ 21 cases/year is associated with a higher likelihood of patients with Stage IIIC/IV epithelial ovarian cancer receiving standard treatment (surgery followed by adjuvant chemotherapy). Even after adjusting for treatment paradigm and other factors, hospital volume ≥ 21 cases/year was significantly predictive of improved overall survival outcome.
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