Repeat surgery plus chemo may improve survival in recurrent ovarian cancer

The DESKTOP* III trial has shown that patients whose ovarian cancer recurs have better overall survival (OS) following secondary cytoreductive surgery plus platinum-based chemotherapy compared with a platinum-based chemotherapy regimen alone.

The researchers enrolled 407 patients with recurrent epithelial ovarian cancer who first relapsed following a platinum chemotherapy-free interval of ≥6 months (75 percent had an interval of >12 months). They were randomized 1:1 to receive platinum-based chemotherapy either alone (non-surgery group; median age 62.2 years) or following secondary cytoreductive surgery (surgery group; median age 60.8 years). To be included, the patients needed to have a positive AGO** score (ECOG performance status score of 0, ascites <500 mL, and complete resection at initial surgery).

The median time between randomization and surgery in the surgery group was 16 days, with chemotherapy initiated a median 35 days post-surgery. In the non-surgery group, chemotherapy was initiated a median 15 days post-randomization. Sixteen percent of patients in the no-surgery group crossed over to receive surgery due to relapse.

Over a median 69.8 months of follow-up, there was a significant improvement in OS among those who underwent cytoreductive surgery plus platinum-based chemotherapy compared with platinum-based chemotherapy alone (median 53.7 vs 46.0 months; hazard ratio [HR], 0.75, 95 percent confidence interval [CI], 0.59–0.96; p=0.02). [N Engl J Med 2021;385:2123-2131]

Among those who underwent secondary cytoreductive surgery, complete resection was achieved in 75.5 percent. These patients appeared to derive the greatest benefit, with a median OS of 61.9 months compared with 27.7 months in patients who did not have complete resection.

The benefits appeared to be consistent regardless of age, International Federation of Gynecology and Obstetrics stage at first diagnosis, tumour histologic subtype, treatment history (including prior maintenance therapy), and platinum-free interval (6–12 months or >12 months).

The median progression-free survival was 18.4 and 14.0 months in the surgery and non-surgery groups, respectively (HR, 0.66, 95 percent CI, 0.54–0.82).

Quality of life (QoL) was assessed at baseline, 6 months, and 12 months post-randomization using the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-C30) and the National Comprehensive Cancer Network Functional Assessment of Cancer Therapy (FACT)–General and FACT–Ovarian and its corresponding FACT–Ovarian Symptom Index.

“[There were no] between-group differences with respect to global health status, QoL, or any functional subscale at baseline, [6 months, or 12 months],” the authors said.

Seven patients required re-operation. No deaths occurred within 30 days post-surgery.

“The standard of care in relapsed ovarian cancer has mainly been systemic treatment,” noted the authors. However, little evidence exists on the OS benefits of systemic therapy in this setting, they added. [Lancet 2003;361:2099-2106; Lancet Oncol 2020;21:699-709]

Aside from the benefits of subsequent cytoreductive surgery in relapsed ovarian cancer noted in the trial, the study highlighted the usefulness of the AGO score.

“All patients with a first relapse after a platinum-free interval of at least 6 months may be evaluated to assess whether surgery is an option, and the AGO score may be incorporated into this process,” the authors said.

“Eligible patients could receive counselling about the options for cytoreductive surgery in centres of gynaecologic oncology that have experience in surgery for relapsed ovarian cancer. In contrast, patients who have a high probability of incomplete resection on the basis of disease or clinical characteristics should not be exposed to a potentially harmful surgical treatment,” they continued.

The authors noted that the results do not apply to patients with ovarian cancer who relapse after more lines of treatment or those who receive interval debulking following chemotherapy, both of which are avenues for future research.