NACT Use Is Growing in Rare Ovarian Cancers, but Certain Patients May Not Benefit


The findings come amidst growing use of the treatment approach.

Neoadjuvant chemotherapy (NACT) may be associated with poorer survival outcomes for certain patients with more uncommon types of epithelial ovarian cancer, suggest study findings, which found that use of the treatment approach has gradually increased.

The findings, published in JAMA Network Open, come amidst a shift in the sequence of chemotherapy and surgery for advanced ovarian cancer. Recent data has suggested that neoadjuvant chemotherapy for advanced ovarian cancer yields outcomes comparable to those from primary debulking surgery. However, data from phase 3 NACT-focused trials have primarily included patients with the most common types of ovarian cancer, leaving knowledge gaps in outcomes among patients with less common subtypes.

“Ovarian cancer is heterogenous, with distinct clinical and biological differences across its histologic subtypes. The most prevalent histologic subtype of epithelial ovarian cancer is high-grade serous carcinomas, and clear cell, low-grade serous, and mucinous carcinomas represent less common histologic subtypes in the US (2%-7%),” explained the researchers. “Due to their rarity, the use and survival outcomes associated with NACT in these less common epithelial carcinomas have been relatively understudied. Even with the available data, limited sample size and lack of comparator groups make their findings difficult to interpret and adopt.”

The researchers of this new study analyzed data from over 3800 patients from the National Cancer Database who had advanced stages of less common ovarian cancers, including clear cell, low-grade serous, or mucinous disease. The group found that among patients with low-grade serous carcinomas, those receiving NACT had worse overall survival (OS) rates at 4 years than those receiving primary surgery (56.4% vs 81%).

Throughout the years studied—2006 and 2017—the use of NACT increased for low-grade serous carcinomas, increasing from 7.7% to 14.2%.

Use also increased among those with clear cell carcinomas, from 10.2% in 2006 to 16.2% in 2017, and among those with mucinous carcinomas, from 8.6% in 2006 to 13.9% in 2017; however, the increase in patients with mucinous carcinomas was statistically nonsignificant. Four-year OS associated with NACT and primary surgery was comparable for both patients with clear cell (31.4% vs 37.7%) and mucinous (27% vs 26.7%) carcinomas.

Additional data from 1400 patients included in the Surveillance, Epidemiology, and End Results Program confirmed the researchers’ findings. OS for the 2 treatment approaches was comparable for patients with clear cell (HR, 0.93; 95% CI, 0.74-1.16) and mucinous (HR, 1.13; 95% CI, 0.72-1.78) carcinomas, while OS was inferior for patients with low-grade serous carcinomas receiving NACT compared with those receiving primary surgery (HR, 3.17; 95% CI, 1.57-6.40).

In this cohort, use of NACT increased from 6.2% to 15.3% in low-grade serous and from 10.2% to 26.1% in clear cell carcinomas between 2006 and 2019. Patients who were older and patients who had stage 4 disease were more likely to receive NACT.

“The reason for the increase in NACT use in less common ovarian cancer subtypes was not assessed in this study, but it is likely multifactorial. The most compelling reason may be the influence of previous phase 3 randomized clinical trials,” noted the researchers.

Based on their findings, amidst growing use of NACT for these more uncommon ovarian cancer subtypes, the researchers suggested the utility of developing clinical practice guidelines and consensus for the role of NACT in this setting.

“The comparable survival outcomes of those studies between NACT and PDS approaches may cause NACT to be favored by surgeons and patients who are not medically optimized for major abdominopelvic surgery," they wrote. "Whether the health care professional and patient knew that less common histologic subtypes represented a small portion of patientsincluded in the earlier trials was not known in this study, warranting further investigation.”


Matsuo K, Matsuzaki S, Maeda M, et al. Uptake and outcomes of neoadjuvant chemotherapy among US patients with less common epithelial ovarian carcinomas. JAMA Netw Open. 2023;6(6):e2318602. doi:10.1001/jamanetworkopen.2023.18602

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