Study: Second surgery may not benefit women with recurrent ovarian cancer

IN-DEPTH REVIEW OF RESEARCH

Study background:

Surgery followed by chemotherapy is the standard of care for treating newly diagnosed ovarian cancer.  While the majority of ovarian cancer patients respond well to primary surgery and chemotherapy, most women (about 80%) develop recurrent disease. While not the standard of care, treating recurrent ovarian cancer with a second surgery followed by chemotherapy is a relatively common practice.

Researchers of this study wanted to know:

Whether a second surgery would increase overall survival among women with platinum-sensitive, recurrent ovarian cancer.

Populations looked at in this study:

Eligible study participants had measurable recurrent platinum-sensitive ovarian cancer who previously chas a omplete clinical response to at least three cycles of platinum-based primary chemotherapy. Patient’s surgeons assessed participants and felt that surgical resection was feasible.

Study design:

From December 2007 through June 2017, patients were randomly assigned to surgery plus chemotherapy or to receive chemotherapy alone. The type of chemotherapy used (paclitaxel-carboplatin or gemcitabine-carboplatin) and the use or not of bevacizumab (Avastin), a non-chemotherapy drug treatment, were up to the investigator. 

• 225 patients had surgery then received chemotherapy.
• 240 patients received chemotherapy only.

Study findings:  

As of April 2019 with a median follow-up of 48 months:

• 197 deaths occurred.
• 135 patients (56%) in the surgery plus chemotherapy group were still alive.
• 153 (62%) in the chemotherapy alone group were still alive.

Patients surviving at three years included 67% in the surgery plus chemotherapy group and 74% in the chemotherapy alone group. Median overall survival was:

• 50.6 months in the surgery plus chemotherapy group.
• 64.7 months in the chemotherapy alone group.

Patients surviving at three years without disease progression included 29% in the surgery plus chemotherapy group compared to 20% in the chemotherapy alone group. Median progression free survival was:

• 18.9 months in the surgery group
• 16.2 months in the chemotherapy alone group

While the median progression-free survival was longer in the surgery plus chemotherapy group compared to the chemotherapy alone, these results are not strong enough to indicate that a combination of surgery plus chemotherapy was superior to chemotherapy alone.

Patient-reported quality of life decreased significantly after surgery.  However, by six weeks post-surgery patient-reported quality of life in the surgery plus chemotherapy group was similar to quality of life reported by patients in the chemotherapy alone group. 

Limitations:

This study had multiple limitations.

First, it is difficult to conduct a clinical trial to evaluate a surgical intervention due to inherent bias in patient selection.  For example, patients who enrolled in this trial had relatively limited tumor volume; more than half had two or fewer sites of recurrent disease.  Patients were also very sensitive to platinum chemotherapy.  These factors likely influenced the effect of a second surgery.

Second, earlier results from this trial and others have shown benefit of bevacizumab (for both adjuvant treatment and maintenance) for women who were treated with a second line of platinum-based chemotherapy.  Some of the patients in this trial did not receive bevacizumab, and it is unclear whether they were less likely to receive bevacizumab in subsequent lines of chemotherapy.  This imbalance in treatment with bevacizumab may have impacted long-term outcomes.

Finally, the median overall survival for everyone in the trial was almost three times longer than expected when the trial was initially designed.  The reasons for this are unknown but are likely due to improvements in clinical care and development of more effective treatments such as PARP inhibitors.  If these factors contributed to increased survival, they may have masked the effect of surgery.

Conclusions:

The findings of this trial suggest that a second surgery while possible may have little to no survival benefit for patients with platinum-sensitive recurrent ovarian cancer.  The European DESKTOP study is also looking at the benefit of surgery plus chemotherapy compared to chemotherapy alone. While the overall survival data for DESKTOP is not yet mature, progression free survival was slightly longer in the surgery plus chemotherapy group, which is similar to the finding in this study. If overall survival in the DESKTOP study is consistent with this study, the question of whether a second surgery has benefit for patients with platinum-sensitive recurrent ovarian cancer should be put to rest. 

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