Erin Crane, MD, MPH

As gynecologic oncologists treating women with recurrent ovarian cancer, we are repeatedly faced with the question: “Why can’t you just take it out again?”

The answer is not so simple.

Several trials have addressed the question of whether secondary cytoreductive surgery offers benefit to these women, and whether specific preoperative criteria can predict the likelihood of such benefit.

The retrospective DESKTOP trial demonstrated an OS benefit among women who underwent “optimal” secondary cytoreduction to less than 1 cm of residual disease. Preoperative ascites less than 500 mL, ECOG performance status of 0 and no residual disease at the time of primary surgery predicted the likelihood of optimal cytoreduction.

This paved the way for DESKTOP II, which prospectively validated DESKTOP and assigned women with a favorable score to secondary cytoreduction, achieving a 75% rate of complete resection.

Thus, DESKTOP III was born, for which researchers randomly assigned women with a favorable score to surgery and chemotherapy vs. chemotherapy alone. OS was improved in the surgery group (median, 53.7 months vs. 46 months), with the most benefit limited to those with no gross residual disease (median, 61.9 months vs. 28.8 months with residual disease).

The much-anticipated results of GOG-213 conflicted with those of DESKTOP III. Similarly, researchers of GOG-213 randomly assigned women with recurrent platinum-sensitive disease to surgery and chemotherapy vs. chemotherapy alone but found no survival benefit to surgery (median OS, 50.6 months vs. 64.7 months). Women assigned to surgery reported an overall decreased quality of life. Interestingly, 84% of women received bevacizumab (Avastin, Genentech) maintenance, compared with 25% of women on the DESKTOP III trial.

Although controversial in the United States, secondary cytoreductive surgery is considered standard of care in China. In the SOC1 trial, Zang and colleagues randomly assigned 365 women with recurrent platinum-sensitive disease with a favorable score to surgery and chemotherapy vs. chemotherapy alone. Median PFS was prolonged in the surgery group (17.4 months vs. 11.9 months), specifically for those women with no residual disease (19.1 months), with 77% of women achieving complete resection.

Although survival data are immature, the 3-year survival rate was 68% with surgery vs. 66% in no-surgery arm.

Notably, the crossover rate was 37% in the no-surgery arm, and 1% of women received bevacizumab maintenance. Although there were no mortalities in the surgery arm, 5.2% of women experienced a grade 3 or worse complication.

How do we put these disparate findings into clinical practice?

GOG-213 suggested that surgery may actually shorten survival but, interestingly, OS in this group exceeded that seen in DESKTOP III. Differences in patient selection, the use of bevacizumab, surgical skill and inherent biases all likely account for the incongruent results.

In short, secondary cytoreduction may benefit a small subset of carefully selected women with small-volume, platinum-sensitive disease who undergo complete gross resection. However, the benefit must be weighed against the risks for surgical harm, decreased quality of life and limitations of imaging in guiding patient selection.

The debate is far from over. 

References:

• Coleman RL, et al. N Engl J Med. 2019;doi:10.1056/NEJMoa1902626.
• Du Bois A, et al. Abstract 6000. Presented at: ASCO20 Virtual Scientific Program; May 29-31, 2020.
• Harter P, et al. Ann Surg Oncol. 2006;doi:10.1245/s10434-006-9058-0.
• Harter P, et al. Int J Gynecol Cancer. 2011;doi:10.1097/IGC.0b013e31820aaafd.