Survival of Australian women with Invasive Epithelial Ovarian Cancer: A Population-based Study.

Objective: To describe survival patterns in a nationally complete cohort of Australian women with epithelial ovarian cancer, by sociodemographic and clinical factors. Design, setting and participants: All 1192 women diagnosed with invasive epithelial ovarian cancer in 2005 were identified through state-based cancer registries. We obtained detailed information from their medical records in 2009 and updated survival data in 2012. Main outcome measures: Crude 3-year, 5-year and 7-year survival rates; 3-year and 5-year conditional survival; and hazard ratios (HRs) for the association of participant and cancer characteristics with survival, from multivariable Cox proportional hazards models. Results: Overall crude 5-year survival was 35% (95% CI, 33%-38%). Conditional survival increased moderately for women who lived beyond a year from diagnosis, although for women alive 2 years after diagnosis, the probability of surviving a further 5 years was still only 53% (95% CI, 49%-57%). Increasing age and disease stage were most strongly associated with poor survival. After adjusting for these, survival was significantly worse for women with carcinosarcomas (HR, 2.1 [95% CI, 1.3-3.2]), clear cell (HR, 1.7 [95% CI, 1.2-2.3]) and mucinous (HR, 2.6 [95% CI, 1.6-4.0]) cancers than for women with serous cancers. Presence of ascites at diagnosis (HR, 1.5 [95% CI, 1.3-1.8]), Charlson comorbidity score ≥ 3 (HR, 1.5 [95% CI, 1.1-2.1]), relative socioeconomic disadvantage (HR, 1.2 [95% CI, 1.1-1.4]) and regional-remote residence (HR, 1.2 [95% CI, 1.0-1.4]) were also associated with poorer survival. Conclusions: Along with expected adverse effects of age and stage, we found survival differences by histological subtype, presence of ascites and comorbidities. Whether geographic and socioeconomic differences relate to treatment access or other factors warrants further investigation. Conditional survival estimates confirm the ongoing poor long-term prognosis for women with ovarian cancer, reinforcing the need for prevention and better treatments

Endometrial cancer risk and survival by tumor MMR status

The risk of developing endometrial cancer (EC) and/or survival following a diagnosis of EC might differ by tumor DNA mismatch repair (MMR) status. We assessed the association between tumor MMR status (classified as MMR-proficient, somatic MMR-deficient, germline MMR-deficient) and the risk of developing EC and survival following a diagnosis of EC.We analyzed data from women who participated in the Australian National Endometrial Cancer Study (ANECS) conducted between 2005 and 2007. Risk analyses (698 cases/691 population controls) utilized sociodemographic and lifestyle information obtained from telephone interviews at recruitment. For survival analyses (728 cases), patients' clinical data was abstracted from medical records, and survival data were obtained via linkage with the Australian National Death Index. We used logistic regression analysis to evaluate the associations between tumor MMR status and EC risk, and proportional hazards models to perform survival analyses with adjustment of known prognostic factors.Established risk factors for EC did not differ significantly by tumor MMR status. In analyses including all EC subtypes, overall and EC-specific survival did not differ by tumor MMR status. Among women with the most common endometrioid subtype, EC-specific survival was worse for women with somatic MMR-deficient EC compared to women with MMR-proficient EC (hazard ratio [HR]=2.18; 95% confidence interval [CI]=1.19-4.01).The risk of EC is not associated with MMR status. Accurate separation of germline from somatic causes of MMR deficiency suggests that patients with endometrioid subtype somatic MMR-deficient tumors have poorer EC-specific survival than those with MMR-proficient tumors, after accounting for other prognostic factors

Homologous Recombination DNA Repair Pathway Disruption and Retinoblastoma Protein Loss Are Associated with Exceptional Survival in High-Grade Serous Ovarian Cancer.

Purpose: Women with epithelial ovarian cancer generally have a poor prognosis; however, a subset of patients has an unexpected dramatic and durable response to treatment. We sought to identify clinical, pathological, and molecular determinants of exceptional survival in women with high-grade serous cancer (HGSC), a disease associated with the majority of ovarian cancer deaths.Experimental Design: We evaluated the histories of 2,283 ovarian cancer patients and, after applying stringent clinical and pathological selection criteria, identified 96 with HGSC that represented significant outliers in terms of treatment response and overall survival. Patient samples were characterized immunohistochemically and by genome sequencing.Results: Different patterns of clinical response were seen: long progression-free survival (Long-PFS), multiple objective responses to chemotherapy (Multiple Responder), and/or greater than 10-year overall survival (Long-Term Survivors). Pathogenic germline and somatic mutations in genes involved in homologous recombination (HR) repair were enriched in all three groups relative to a population-based series. However, 29% of 10-year survivors lacked an identifiable HR pathway alteration, and tumors from these patients had increased Ki-67 staining. CD8+ tumor-infiltrating lymphocytes were more commonly present in Long-Term Survivors. RB1 loss was associated with long progression-free and overall survival. HR deficiency and RB1 loss were correlated, and co-occurrence was significantly associated with prolonged survival.Conclusions: There was diversity in the clinical trajectory of exceptional survivors associated with multiple molecular determinants of exceptional outcome in HGSC patients. Concurrent HR deficiency and RB1 loss were associated with favorable outcomes, suggesting that co-occurrence of specific mutations might mediate durable responses in such patients. Clin Cancer Res; 24(3); 569-80. ©2017 AACRSee related commentary by Peng and Mills, p. 508