Abstract
No data exist regarding whether any first-line treatment for metastatic uveal melanoma provides overall survival (OS) benefit, if staged and compared to best supportive care (BSC). We analyzed OS in a nationwide, consecutive cohort diagnosed with metastatic uveal melanoma between January 1999 and December 2016. The Helsinki University Hospital Working Formulation was used to assign patients to stage IVa, IVb and IVc, corresponding to predicted median OS ≥12, <12-6 and <6 months, respectively. OS of 216 actively treated patients was compared by treatment and working formulation stage against 108 similarly staged, concurrent patients managed with BSC using Kaplan-Meier analysis and Cox regression. The median OS with active treatment was 18 (range, 0.7-162), 6.9 (range, 1.3-30) and 1.9 (range, 0.2-18) months in working formulation stage IVa, IVb and IVc, respectively. Patients who received chemoimmunotherapy, selective internal radiation therapy, or underwent surgical resection survived longer - median OS 13, 16 and 24 months, respectively - than those receiving conventional chemotherapy - median OS 5.1 months - but only with surgical resection their OS exceeded that with BSC, both overall and in stage IVa (P < 0.001, P = 0.010). In stage IVb and IVc, no difference in OS was observed in any comparison. Staging of patients is crucial when comparing survival after metastatic uveal melanoma. Only surgical resection for stage IVa disease provided longer OS in our national cohort. We additionally recommend stage-specific comparison of novel treatments against available BSC data.
Highlights
IntroductionThe liver is the most common first site, and local treatments have been suggested to prolong [3,4,5,6] the otherwise limited median overall survival (OS) of approximately 13 months [1,7]
More than half of patients with primary uveal melanoma develop metastases [1,2]
Treatment categories Based on our previous meta-analysis [7], we prospectively identified the following systemic treatment modalities: conventional chemotherapy, chemoimmunotherapy, checkpoint inhibitors (CPI), protein kinase inhibitors (PKI) and vaccine therapies
Summary
The liver is the most common first site, and local treatments have been suggested to prolong [3,4,5,6] the otherwise limited median overall survival (OS) of approximately 13 months [1,7]. The largest one found among 171 patients no difference in OS between intravenous and intra-arterial fotemustine, a chemotherapeutic agent that concentrates in the liver [8]. One registry study of 175 patients of whom 106 received active treatment was nationwide [14]. The other four were cohorts from single tertiary referral centers with 62–539 actively treated patients [4,6,15,16]. The key limitation common to them was that patients were not staged and often lacked a proper control group.
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