Durable outcomes in aggressive-variant prostate cancer treated with first-line carboplatin–docetaxel: A 10-year tertiary centre experience.

Abstract

93 Background: Aggressive-variant prostate cancer (AVPC) is a rare but clinically significant subset of prostate cancer, often emerging after hormone therapy. There is no accepted first-line regimen for AVPC but often responds to platinum-based therapy. Carboplatin-docetaxel (CARBO-DOCE) is a recognised option with promising phase 2 results, but long-term outcomes are poorly defined. Methods: We retrospectively identified patients treated with both de-novo hormone-naïve (DN-AVPC) and treatment-emergent castrate-resistant AVPC (CR-AVPC) who received first-line CARBO-DOCE between 2015 and 2025. AVPC was defined with Aparicio et al’s (2013) criteria. Overall (OS) and progression-free survival (PFS) were estimated using Kaplan-Meier and univariate Cox regression. Due to presence of PSA non-secretors, biochemical response (BR50) was defined as a 50% reduction in PSA, CEA, and/or LDH. Results: 36 patients with AVPC were identified (23 CR-AVPC; 13 DN-AVPC). Baseline age (73 vs 74 years; p =0.7) and PSA (1.77 vs 9.72ng/mL; p =0.4) were similar in both groups. 36.3% and 22.2% had a performance status (PS) of 2 and 3 respectively. CR-AVPC was associated with higher rates of liver metastases (57% vs 15%; p =0.016 ) and anaemia (Hb 104 vs 131g/L, p =0.005 ). 34.8% of CR-AVPC patients had ≥2 prior therapy lines including AR pathway inhibitor (ARPI) (30.4%) and docetaxel (17.4%). Compared with DN-AVPC, CR-AVPC had shorter median OS (8.7 vs N.R months; p <0.001) and PFS (5.0 vs 15.5 months; p =0.001). Of the biomarker secretors in CR-AVPC (n=17/23) and DN-AVPC (n=8/13), BR50 occurred in 64.7% and 75.0% respectively. In non-secretors, overall response rate was 50% and 75% respectively. Univariate analysis showed only baseline Hb and albumin to be prognostic for OS in CR-AVPC. PS 2-3 did not correlate with inferior OS (HR 1.93; 95%CI 0.82-4.54) and PFS (HR 1.57; 95%CI 0.74-3.34). Median number of cycles were 4. Dose reductions occurred in 27.8% cases. 77.8% had grade ≥3 adverse events; commonly neutropenia (44.4%), anaemia (30.6%), and fatigue (13.9%). One death occurred from neutropenic sepsis. Of those who progressed, 50% and 88.9% received second-line treatment. In the CR-AVPC group, BR50 occurred with epirubicin-carboplatin-capecitabine (n=3/3) and cisplatin-etoposide (cis-etop) (n=2/2). Post-second line, there was no response to cis-etop (n=2/2), ARPI (n=2/2), or Lu-177 (n=1/1). BR50 occurred with diethylstilbestrol-dexamethasone (DAS) in second- and third-line (n=2/2). Conclusions: CARBO-DOCE achieves respectable response as first-line regimen for AVPC. DN-AVPC had higher chemosensitivity, suggesting biological differences. Platinum-rechallenge with other combinations achieved high response rates. Intriguingly, two CR-AVPC cases responded to DAS but not ARPIs, suggesting some sensitivity to oestrogen-based therapy in this heterogenous group.