Neoadjuvant Chemotherapy Optimal for Subset of Patients With Ovarian Cancer

While some women with ovarian cancer will benefit most from primary cytoreductive surgery (PCS), the optimal treatment for others is likely neoadjuvant chemotherapy, according to a report that was recently published in the Journal of Clinical Oncology.

This observational study found that patients with stage 3C disease who neoadjuvant chemotherapy had significantly decreased overall survival (OS) compared with those treated with PCS (median, 33 vs 43 months). Among patients with stage 4 disease, however, there was no significant difference in OS (median, 31 vs 36 months).

“Our results suggest that primary cytoreductive surgery may improve survival for patients with stage 3C ovarian cancer who are likely to achieve an optimal cytoreduction, while neoadjuvant chemotherapy may be the preferred option for many women with stage 4 ovarian cancer,” Larissa A. Meyer, M.D., assistant professor, Department of Gynecologic Oncology and Reproductive Medicine, Division of Surgery, The University of Texas MD Anderson Cancer Center, said in an interview with CURE.

These results are consistent with a subset analysis in the EORTC study, which demonstrated improved survival in patients with stage 3C disease and less than 45 mm of disease who received PCS versus neoadjuvant chemotherapy .

The current study examined the use of neoadjuvant chemotherapy , as well as outcomes associated with it, at six National Cancer Institute—designated cancer centers between 2003 and 2012. Patients were assigned to a treatment arm (neoadjuvant chemotherapy or PCS) on the basis of whether they initially received chemotherapy or surgery.

In the first cohort of patients, the authors examined neoadjuvant chemotherapy use over time among 1,538 patients diagnosed between 2003 and 2012 and treated within 12 weeks of diagnosis. In the second cohort, the goal was to examine factors and outcomes associated with neoadjuvant chemotherapy versus PCS within a subset of 1,158 patients from the first cohort. This subset excluded patients who had received intraperitoneal and intravenous (IP/IV) chemotherapy, as few patients treated with neoadjuvant chemotherapy receive IP/IV chemotherapy, and it is associated with its own independent survival benefit.

The results of the study showed that, between 2003 and 2011, the use of neoadjuvant chemotherapy increased steadily over time from 16 percent to 34 percent among patients with stage 3C ovarian cancer, and from 41 percent to 62 percent among patients with stage 4 disease.

The authors noted that the degree of variation in the use of neoadjuvant chemotherapy between such similar academic institutions suggests that uptake of neoadjuvant chemotherapy is influenced by local culture, clinical practice leaders within institutions and maybe even patients’ preferences.

PCS was found to be associated with significantly improved survival in women with stage 3C, but not stage 4 disease, compared with neoadjuvant chemotherapy .

Patients with stage 3C and 4 disease treated with neoadjuvant chemotherapy were more likely to achieve more than 1 cm or microscopic residual disease after interval cytoreductive surgery (ICS) compared with PCS. However, few differences were found in complexity, aggressiveness, or complications of surgery.

The authors wrote that it was important to note that, although patients with stage 3C disease who received neoadjuvant chemotherapy were significantly more likely to have less than 1 cm or R0 microscopic residual disease after ICS, this finding was not associated with a survival benefit.

In contrast, patients who achieved less than 1 cm of residual disease after PCS, rather than neoadjuvant chemotherapy and ICS, had significantly longer survival. Future research should prospectively compare the survival outcomes of patients treated with PCS versus neoadjuvant chemotherapy stratified by residual disease after surgery, according to the authors.

These results come shortly after the publication of ASCO’s new neoadjuvant chemotherapy ovarian cancer guideline, which recommends neoadjuvant chemotherapy as the optimal first-line treatment for some women with newly diagnosed, advanced ovarian cancer.

“The findings in our study are aligned with the recently issued ASCO/SGO guideline for neoadjuvant chemotherapy,” said Meyer.

One of the guideline recommendations states that neoadjuvant chemotherapy is favored over PCS for women who are fit for PCS, but are also deemed unlikely to achieve cytoreduction to less than 1 cm (ideally to no visible disease) by a gynecologic oncologist. Meyer says the findings of the current study support that recommendation.

The choice between PCS and neoadjuvant chemotherapy remains highly controversial, as the optimal treatment of advanced ovarian cancer includes both surgical cytoreduction and platinum-based chemotherapy.

“The bottom line is a one-size-fits-all strategy no longer works for treatment of ovarian cancer,” said Meyer.