Abstract
BackgroundAfter radical resection, patients with adrenocortical carcinoma (ACC) frequently experience recurrence and, therefore, effective adjuvant treatment is urgently needed. The aim of the study was to investigate the role of adjuvant platinum-based therapy.MethodsIn this retrospective multicentre cohort study, we identified patients treated with adjuvant platinum-based chemotherapy after radical resection and compared them with patients without adjuvant chemotherapy. Recurrence-free and overall survival (RFS/OS) were investigated in a matched group analysis and by applying a propensity score matching using the full control cohort (n = 268). For both approaches, we accounted for immortal time bias.ResultsOf the 31 patients in the platinum cohort (R0 n = 25, RX n = 4, R1 n = 2; ENSAT Stage II n = 11, III n = 16, IV n = 4, median Ki67 30%, mitotane n = 28), 14 experienced recurrence compared to 29 of 31 matched controls (median RFS after the landmark at 3 months 17.3 vs. 7.3 months; adjusted HR 0.19 (95% CI 0.09–0.42; P < 0.001). Using propensity score matching, the HR for RFS was 0.45 (0.29–0.89, P = 0.021) and for OS 0.25 (0.09–0.69; P = 0.007).ConclusionsOur study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence.
Highlights
Adrenocortical carcinoma (ACC) is a rare and aggressive disease with limited therapeutic options and a high rate of recurrence even after complete resection [1,2,3,4,5]
Our study provides the first evidence that adjuvant platinum-based chemotherapy may be associated with prolonged recurrence-free and overall survival in patients with ACC and a very high risk for recurrence
In comparison to the entire control group, the median Ki67 index was higher (30% vs. 20%, P = 0.008), more patients had ENSAT tumour Stages III and IV, and more patients were treated with adjuvant mitotane in the platinum-based chemotherapy group
Summary
Adrenocortical carcinoma (ACC) is a rare and aggressive disease with limited therapeutic options and a high rate of recurrence even after complete resection [1,2,3,4,5]. Mitotane is the only drug approved for the treatment of advanced ACC and is used as adjuvant therapy [1, 7,8,9,10,11]. All published data on adjuvant mitotane are retrospectively collected, and randomised trials are lacking. The recruitment of the prospective randomised ADIUVO trial (NCT00777244), investigating the efficacy of adjuvant mitotane versus observation only in patients with low-intermediate risk of recurrence is stopped, but the results are still pending. Awaiting the results of the ADIUVO trail, both the comprehensive ESE-ENSAT guidelines 2018 and the new ESMO-EURACAN guidelines 2020 recommend an adjuvant treatment with mitotane in patients who have a high risk of recurrence (i.e., Stage III or IV, R1 or RX resection, or Ki67 >10%) [1, 9]. The recurrence rate is still about 50% even after mitotane treatment [7]
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