Effect of docetaxel added to bicalutamide in Hormone-Naïve non-metastatic prostate cancer with rising PSA, a randomized clinical trial (SPCG-14)

Historically, endocrine therapy was used in a range of scenarios in patients with rising PSA, both as a treatment for locally advanced non-metastatic prostate cancer and PSA recurrence following curative intended therapy. In the present study the objective was to investigate if chemotherapy added to endocrine therapy could improve progression-free survival (PFS).
Patients with hormone-naïve, non-metastatic prostate cancer and rising prostate-specific antigen (PSA), enrolled from Sweden, Denmark, the Netherlands, and Finland, were randomized to long-term bicalutamide (150 mg daily) or plus docetaxel (75 mg/m2, q3w, 8–10 cycles) without prednisone, after stratification for the site, prior local therapy or not, and PSA doubling time. The primary endpoint was 5-year PFS analyzed with a stratified Cox proportional hazards regression model on intention to treat basis.
Between 2009 and 2018, a total of 348 patients were randomized; 315 patients had PSA relapse after radical treatment, 33 patients had no prior local therapy. Median follow-up was 4.9 years (IQR 4.0–5.1). Adding docetaxel improved PFS (HR 0.68, 95% CI 0.50–0.93; p = 0.015). Docetaxel showed an advantage for patients with PSA relapse after prior local therapy (HR 0.67, 95% CI 0.49–0.94; p = 0.019). One event of neutropenic infection/fever occurred in 27% of the patients receiving docetaxel. Limitations were slow recruitment, lack of enrolling patients without radical local treatment, and too short follow-up for evaluation of overall survival in patients with PSA relapse.
Docetaxel improved PFS in patients starting bicalutamide due to PSA relapse after local therapy or localized disease without local therapy. Confirmatory studies of the efficacy of docetaxel in the setting of PSA-only relapse in addition to endocrine therapies may be justified if longer follow-up will show increased metastatic-free survival.

长期以来，前列腺特异性抗原（prostate-specific antigen, PSA）升高患者的内分泌治疗应用场景广泛，既可用于局部进展性非转移性前列腺癌的治疗，也可用于根治性意向治疗后出现PSA复发的患者。本研究旨在探讨在内分泌治疗基础上加用化疗能否改善无进展生存期（progression-free survival, PFS）。
本研究纳入来自瑞典、丹麦、荷兰及芬兰的激素初治、非转移性前列腺癌且PSA升高的患者，按研究中心、是否接受过局部治疗及PSA倍增时间进行分层后，随机分为两组：一组接受长期比卡鲁胺（每日150mg）治疗，另一组在比卡鲁胺基础上加用多西他赛（75mg/m²，每3周1次（q3w），共8~10个周期），且两组均不使用泼尼松。本研究的主要终点为基于意向性治疗分析，采用分层Cox比例风险回归模型评估的5年PFS。
2009年至2018年间，共计348例患者被随机分组；其中315例患者在根治性治疗后出现PSA复发，33例患者未接受过局部治疗。中位随访时间为4.9年（四分位距4.0~5.1年）。加用多西他赛可改善患者的无进展生存期（风险比0.68，95%置信区间0.50~0.93；p=0.015）。对于既往接受过局部治疗后出现PSA复发的患者，多西他赛展现出明确获益优势（风险比0.67，95%置信区间0.49~0.94；p=0.019）。接受多西他赛治疗的患者中，27%发生了中性粒细胞减少性感染/发热事件。本研究的局限性包括入组速度缓慢、未纳入未接受根治性局部治疗的患者，以及随访时间过短，无法有效评估PSA复发患者的总生存期。
对于因局部治疗后PSA复发或未接受局部治疗的局限性前列腺癌而启动比卡鲁胺治疗的患者，多西他赛可改善其无进展生存期。若更长时间的随访结果显示患者无转移生存期得以延长，则有必要开展确证性研究，以评估在内分泌治疗基础上加用多西他赛对仅出现PSA复发患者的临床疗效。