Characteristics and outcome of recurrence in molecularly defined adult-type ovarian granulosa cell tumors

abstract

Highlights

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Tumor rupture is the strongest predictive factor for AGCT recurrence.

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AGCT requires active follow up for ten to fifteen years after primary diagnosis.

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Recurrences may develop asymptomatically and in multiple anatomical locations.

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Recurrences significantly increase disease-related mortality.

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Objective

Adult-type ovarian granulosa cell tumors (AGCTs) have an unpredictable tendency to relapse. In a carefully validated patient cohort, we evaluated the prognostic factors related to AGCT recurrence.

Methods

We identified all patients diagnosed with AGCT during 1956–2014 in Helsinki University Hospital, with a minimum follow-up of one year (n = 240). After a histological review supplemented with FOXL2 (402C-G) mutation status analysis, we analyzed the clinical data for association with relapse.

Results

The final cohort included 164 (68%) molecularly defined AGCTs (MD-AGCTs). The majority of the women were postmenopausal (63%), and 92% of tumors were stage I. The median follow-up time was 15.5 years. Fifty-two (32%) patients developed tumor recurrence, of whom 55% had successive recurrences. Multiple-site recurrences were common, and nearly half of the recurrences were asymptomatic. The median time to the first relapse was 7.4 years, and 75% of relapses occurred within ten years after primary diagnosis. The median disease-free survival was 11.3 years. Premenopausal status at initial diagnosis, FIGO stage Ic versus Ia, and tumor rupture associated with relapse. However, tumor rupture was the only independent predictive factor. Of the relapsed patients, 48% died of AGCT in a median time of 15.3 years.

Conclusion

Tumor rupture is the strongest predictive factor for recurrence, and these patients might benefit from a more aggressive initial treatment approach. AGCT requires active follow up for 10 to 15 years after primary diagnosis, since recurrences may develop late, asymptomatically and in multiple anatomical locations.