Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery

Abstract

Objective: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) confers similar outcomes as primary debulking surgery and chemotherapy. Little is known about patients who receive NACT but do not undergo debulking surgery. Our aim was to characterize these patients. Methods: We prospectively identified patients with newly diagnosed stage III/IV ovarian cancer treated with NACT from 7/1/15-12/1/17. Fisher exact and Wilcoxon rank-sum tests were used to compare clinical characteristics by surgical status. The Kaplan-Meier method was used to estimate survival outcomes. Log-rank test and Cox proportional hazards model were applied to assess the relationship of covariates to outcome, and time-dependent covariates were applied to variables collected after diagnosis. Results: Of 224 women who received NACT, 162 (72%) underwent IDS and 62 (28%) did not undergo surgery. The non-surgical group was older (p<0.001), had higher Charlson comorbidity index (CCI; p<0.001), lower albumin levels (p=0.007), lower Karnofsky performance scores (p<0.001), and were more likely to have dose reductions in NACT (p<0.001). Reasons for no surgery included poor response to NACT (39%), death (15%), comorbidities (24%), patient preference (16%), and loss to follow-up (6%). The no surgery group had significantly worse overall survival (OS) than the surgery group (hazard ratio=3.34; 95% confidence interval=1.66-6.72; p<0.001), after adjustment for age, CCI, and dose reductions. Conclusions: A significant proportion of women treated with NACT do not undergo IDS, and these women are older, frailer, and have worse OS. More studies are needed to find optimal therapies to maximize outcomes in this high-risk, elderly population.

Neoadjuvant chemotherapy for advanced ovarian cancer: the tail of the scorpion for radical debulking surgery?

“…Real-life reports indicate that more than a quarter of women with advanced ovarian cancer who are treated with neoadjuvant chemotherapy do not ever reach the point of being able to undergo cytoreductive surgery at an interval setting. 5 Even though cytoreductive surgery is the gold standard of national and international guidelines, in actual practice a considerable proportion of patients with advanced ovarian cancer will not have any surgery at all as part of their initial management. 1 The UK National Cancer Data Repository reports that around 40% of patients with newly diagnosed advanced ovarian cancer have never undergone debulking surgery of any timing, with up to 25% receiving palliative care alone.…”

“…As per our intuitive expectation, it has been shown that patients who never underwent surgery had a more than threefold increase in all-cause mortality compared with those who underwent surgery at some point in their disease journey, even after risk adjustment for age, tumor dissemination patterns, and dose reductions. 5 Hence, our focus as gynecological oncology experts for now is not just to have endless debates and hypotheses about the timing of surgery in advanced disease; the prospectively randomized phase III international TRUST trial (AGO-OVAR-OP.7/NCT02828618) has Editorial been perfectly designed to answer this in appropriately specialized settings with adequate experience in radical debulkings despite the high tumor load. 6 Our goal should be to direct patients with advanced disease to expert dedicated centers that will be able to adequately treat them, despite their high tumor load, and the challenges arising from that.…”

How to predict treatment failure in frail patients with advanced epithelial ovarian cancer: strategies to personalize surgical effort

“…In this issue by Liu et al [8], the team from Memorial Sloan Kettering Cancer Center has demonstrated that more than a quarter of women with advanced EOC who are treated with neoadjuvant chemotherapy (NACT) do not ever reach the point of being able to undergo cytoreductive surgery at an interval setting (IDS). Advanced age, lower albumin levels, frailty scores and extensive disease of predominantly high-grade serous histology, were identified as the most significant risk factors for inability to undergo surgery.…”

“…Advanced age, lower albumin levels, frailty scores and extensive disease of predominantly high-grade serous histology, were identified as the most significant risk factors for inability to undergo surgery. The reasons of that were mainly quoted as 1) extent of disease not amenable to surgery or lack of response to NACT; 2) patient comorbidities preventing surgery; 3) both extent of disease and patient comorbidity [8]. The findings of this study confirmed the intuitive expectation that these, never operated, patients will have a >3-fold increase in all-cause mortality compared to those who underwent surgery at some point in their journey, even after risk adjustment for age, tumor dissemination patterns and dose reductions.…”

“…In times of significant and continuous increase of the elderly population worldwide and hence the increased average age of the patients that we, as gynecological oncology community, are called to treat, it is high time we developed and established validated geriatric scores for the adequate stratification of our patients. In the paper by Liu et al [8] 74% of the patients in the non-surgical group was ≥70 years of age compared with only 36% in the surgical group. The non-surgical group was also on average 8.8 years older compared to the surgical group; data correlating with similar experiences in numerous other studies, where the aging population represents a considerate challenge in the implementation of traditional treatment strategies [8].…”