Trends in peritoneal cytology evaluation at hysterectomy for endometrial cancer in the United States.

OBJECTIVE: The collection of a peritoneal cytologic sample at the time of surgery for endometrial cancer has traditionally been an important part of surgical staging. In 2009, the International Federation of Gynecology and Obstetrics revised the cancer staging schema for endometrial cancer and removed peritoneal cytology from the staging criteria. The current National Comprehensive Cancer Network guidelines and the International Federation of Gynecology and Obstetrics organization, however, recommend evaluation of peritoneal cytology at the time of hysterectomy. This study examined population-based trends, characteristics, and outcomes of peritoneal cytologic sampling for endometrial cancer surgery following the 2009 staging revision in the United States. METHODS: This is a retrospective observational study querying the Surveillance, Epidemiology, and End Results Program to examine women with stage I-III endometrial cancer who underwent hysterectomy from 2010 to 2017. Trends, characteristics, and survival associated with peritoneal cytologic evaluation at the time of hysterectomy were assessed in multivariable analysis and with propensity score weighting. RESULTS: Among 62,809 women who underwent hysterectomy, 43,873 (69.9%) had peritoneal cytologic evaluation at surgery and 18,936 (30.1%) did not. Utilization of peritoneal cytologic evaluation decreased from 75.5% to 64.9% during the study period (P < 0.001). In multivariable analysis, more recent year of surgery was independently associated with a decreased likelihood of performance of peritoneal cytology (adjusted-odds ratio of peritoneal cytology evaluation in 2017 versus 2010 0.56, 95% confidence interval [CI] 0.52-0.60). Peritoneal cytologic evaluation at the time of hysterectomy was associated with improved all-cause mortality (hazard ratio in the whole cohort 0.94, 95%CI 0.89-0.99; and hazard ratio in endometrioid histology 0.90, 95%CI 0.84-0.97). CONCLUSION: Performance of peritoneal cytologic sampling has gradually decreased following the 2009 staging revision in the United States. Our study suggests that peritoneal cytology evaluation at hysterectomy may be associated with improved survival in certain tumor groups.

Hyperthermic intraperitoneal chemotherapy does not improve survival in advanced ovarian cancer.

Despite its widespread use, until recently, there was no randomized evidence for hyperthermic intraperitoneal chemotherapy (HIPEC) versus surgery without HIPEC for ovarian cancer. Recently, a Dutch study (OVHIPEC) reported benefits in both progression-free survival (PFS) and overall survival (OS) gained from the use of HIPEC at the time of interval debulking surgery (IDS) for stage III ovarian carcinoma, whereas a Korean randomized trial failed to show a benefit of HIPEC for patients with ovarian cancer undergoing primary debulking surgery or IDS. In colorectal cancer, 2 randomized trials failed to show an improvement in survival with HIPEC. In addition to these contradictory results, there are a number of aspects of the Dutch OVHIPEC trial in ovarian cancer that can be criticized. Some criticisms include a reduction of the number of patients needed to be randomized because of too slow accrual; much lower PFS and OS in both arms than expected according to the statistical plan; the small size of the study, with imbalances between the 2 arms (eg, more low-grade tumors in the HIPEC arm); the timing of randomization before the start of IDS; the lack of clear inclusion criteria for neoadjuvant chemotherapy; and the heterogeneity of the results, with the largest effect shown at the smaller centers. Furthermore, it is questionable whether the adverse events were reported completely. In conclusion, data about HIPEC for ovarian cancer in general are not convincing, and they do not change the standard of care, which remains for ovarian cancer surgery and intravenous chemotherapy.

Is there a role for HIPEC in ovarian cancer?

Hyperthermic intraperitoneal chemotherapy (HIPEC) is promoted by some as a standard treatment for peritoneal carcinomatosis of epithelial ovarian cancer (EOC) and other tumor entities, despite lack of robust data supporting this. Publicly available evidence addressing the value of HIPEC in EOC is rather inconclusive, revealing contradictory and inconsistent results while some studies even report harm to the patients from a higher morbidity. On this ground, we cannot recommend the implementation and use of HIPEC outside of a randomized clinical trial setting.

Sorafenib plus topotecan versus placebo plus topotecan for platinum-resistant ovarian cancer (TRIAS): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: Antiangiogenic therapy has known activity in ovarian cancer. The investigator-initiated randomised phase 2 TRIAS trial assessed the multi-kinase inhibitor sorafenib combined with topotecan and continued as maintenance therapy for platinum-resistant or platinum-refractory ovarian cancer. METHODS: We did a multicentre, double-blind, placebo-controlled, randomised, phase 2 trial at 20 sites in Germany. Patients (≥18 years) with platinum-resistant ovarian cancer previously treated with two or fewer chemotherapy lines for recurrent disease were stratified (first vs later relapse) in block sizes of four and randomly assigned (1:1) using a web-generated response system to topotecan (1·25 mg/m2 on days 1-5) plus either oral sorafenib 400 mg or placebo twice daily on days 6-15, repeated every 21 days for six cycles, followed by daily maintenance sorafenib or placebo for up to 1 year in patients without progression. Investigators and patients were masked to allocation of sorafenib or placebo; topotecan treatment was open label. The primary endpoint was investigator-assessed progression-free survival, analysed in all patients who received at least one dose of study drug. This completed trial is registered with ClinicalTrials.gov, number NCT01047891. FINDINGS: Between Jan 18, 2010, and Sept 19, 2013, 185 patients were enrolled, 174 of whom were randomly assigned: 85 to sorafenib and 89 to placebo. Two patients in the sorafenib group had serious adverse events before treatment and were excluded from analyses. 83 patients in the sorafenib group and 89 in the placebo group started treatment. Progression-free survival was significantly improved with sorafenib versus placebo (hazard ratio 0·60, 95% CI 0·43-0·83; p=0·0018). Median progression-free survival was 6·7 months (95% CI 5·8-7·6) with sorafenib versus 4·4 months (3·7-5·0) with placebo. The most common grade 3-4 adverse events were leucopenia (57 [69%] of 83 patients in the sorafenib group vs 47 [53%] of 89 in the placebo group), neutropenia (46 [55%] vs 48 [54%]), and thrombocytopenia (23 [28%] vs 20 [22%]). Serious adverse events occurred in 49 (59%) of 83 sorafenib-treated patients and 45 (51%) of 89 placebo-treated patients. Of these, events were fatal in four patients (5%) in the sorafenib group (dyspnoea and poor general condition, septic shock, ascites and dyspnoea, and sigma perforation) and seven (8%) in the placebo group (pulmonary embolism in two patients, disease progression in two patients, and one case each of sepsis with fever, pleural effusion, and tumour cachexia). Sorafenib was associated with increased incidences of grade 3 hand-foot skin reaction (three [13%] vs 0 patients) and grade 2 alopecia (24 [29%] vs 12 [13%]). INTERPRETATION: Sorafenib, when given orally in combination with topotecan and continued as maintenance therapy, showed a statistically and clinically significant improvement in progression-free survival in women with platinum-resistant ovarian cancer. These encouraging results support the crucial role of antiangiogenesis as the treatment backbone in combination with chemotherapy, making this approach attractive for further assessment with other targeted strategies. FUNDING: Bayer, Amgen, and GlaxoSmithKline.

Brief Report About the Role of Hyperthermic Intraperitoneal Chemotherapy in a Prospective Randomized Phase 3 Study in Recurrent Ovarian Cancer From Spiliotis et al.

A published so-called phase 3 study regarding HIPEC in ovarian cancer raised multiple questions. This commentary focusses on the weakness of the publication and discusses this in detail.