Conteduca Vincenza, Di Tullio Piergiorgio, Allamprese Rossana, Bruno Giuseppina, Lolli Cristian, Schepisi Giuseppe, Rosano Aldo, Giordano Guido, Garofoli Marianna, Chiuri Vincenzo Emanuele, Fratino Lucia, Zanardi Elisa, Galli Luca, Massari Francesco, Falagario Ugo, Rescigno Pasquale, Fornarini Giuseppe, Sanguedolce Francesca, Santini Daniele, Procopio Giuseppe, Caffo Orazio, Carrieri Giuseppe, Landriscina Matteo, De Giorgi Ugo
Unit of Medical Oncology and Biomolecular Therapy, Department of Medical and Surgical Sciences, University of Foggia, Policlinico Riuniti, 71122, Foggia, Italy.
Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCSCROB), Rionero in Vulture, Italy.
Prostate Cancer Prostatic Dis. 2025 Jun;28(2):370-377. doi: 10.1038/s41391-024-00800-8. Epub 2024 Feb 12.
Currently, several therapies are available for metastatic castration-resistant prostate cancer (mCRPC) but no specific clinical factors to personalize treatment. We first sought the prognostic value of duration on androgen-deprivation therapy (ADT) for hormone-sensitive prostate cancer (HSPC) in patients receiving androgen-receptor-signaling inhibitors (ARSI) for mCRPC.
A multicenter cohort of mCRPC patients who started ARSI between July 2011 and October 2021 was identified. Based on their initial disease burden and duration on ADT for HSPC, primary progressive (PP) men were classified into four groups: low/intermediate-risk localized disease (LOC) and high-risk localized/locally advanced disease (LAD) and short-term (ST) < 24 vs. long-term (LT) ADT ≥ 24 months, whereas de novo (DN) mHSPC were subdivided into short-time vs. long-time to CRPC.
We included 919 mCRPC patients with a median age of 77 years [interquartile range (IQR) = 71-82)]. Median ADT duration in HSPC was 24 months (IQR = 14-40). Median follow-up was 91 months (IQR = 62-138), median OS and PFS from ARSI start were 20 (IQR 10-32) and 10 months (IQR = 5-19), respectively. In PP developing metastatic disease (n = 655, 71.3%), LOC and LAD with ST ADT had a greater than almost double-risk of death compared to LT ADT (LOC/ST: hazard ratio [HR] = 2.01; 95% CI 1.54-2.64; LAD/ST: HR = 1.73; 95% CI 1.34-2.24; p < 0.001). In the multivariate analysis including age, prognostic cohort, Gleason, ECOG, radical radiotherapy and prostatectomy, groups with ST ADT were associated with worse OS compared to LT ADT (LOC/ST: HR = 1.84; 95% CI 1.38-2.45; p < 0.001; LAD/ST: HR = 1.59; 95% CI 1.21-2.10; p < 0.001), along with ECOG > 2 (HR = 1.55; 95% CI 1.06-2.26; p = 0.03). There were also similar results of PFS. Moreover, long-time to CRPC in patients with history of DN mHSPC (n = 264, 28.7%) resulted in a better OS/PFS (HR = 0.76, 95% CI 0.56-1.02, p = 0.064 and HR = 0.74, 95% CI 0.55-0.99, p = 0.042, respectively).
Our study showed that duration on ADT for mHSPC was significantly associated with survival in mCRPC undergoing ARSI. These findings suggest a possible connection between initial management of prostate tumour and a better prognostication in mCRPC. Prospective trials are warranted.
目前，转移性去势抵抗性前列腺癌（mCRPC）有多种治疗方法，但尚无用于个性化治疗的特定临床因素。我们首先探讨了激素敏感性前列腺癌（HSPC）接受雄激素剥夺治疗（ADT）的持续时间对接受雄激素受体信号抑制剂（ARSI）治疗的mCRPC患者的预后价值。
确定了一个多中心队列的mCRPC患者，他们在2011年7月至2021年10月期间开始使用ARSI。根据他们最初的疾病负担和HSPC接受ADT的持续时间，原发性进展（PP）男性被分为四组：低/中风险局限性疾病（LOC）和高风险局限性/局部进展性疾病（LAD），以及短期（ST）<24个月与长期（LT）ADT≥24个月，而新发（DN）mHSPC则细分为至CRPC的短时间与长时间。
我们纳入了919例mCRPC患者，中位年龄为77岁[四分位间距（IQR）=71-82]。HSPC中ADT的中位持续时间为24个月（IQR=14-40）。中位随访时间为91个月（IQR=62-138），从开始使用ARSI起的中位总生存期（OS）和无进展生存期（PFS）分别为20个月（IQR 10-32）和10个月（IQR=5-19）。在发生转移性疾病的PP患者中（n=655，71.3%），与LT ADT相比，ST ADT的LOC和LAD患者死亡风险几乎高出一倍以上（LOC/ST：风险比[HR]=2.01；95%置信区间1.54-2.64；LAD/ST：HR=1.73；95%置信区间1.34-2.24；p<0.001）。在包括年龄、预后队列、Gleason评分、美国东部肿瘤协作组（ECOG）评分、根治性放疗和前列腺切除术的多变量分析中，与LT ADT相比，ST ADT组的OS更差（LOC/ST：HR=1.84；95%置信区间1.38-2.45；p<0.001；LAD/ST：HR=1.59；95%置信区间1.21-2.10；p<0.001），同时ECOG>2时也是如此（HR=1.55；95%置信区间1.06-2.26；p=0.03）。PFS也有类似结果。此外，有DN mHSPC病史的患者（n=264，28.7%）至CRPC的时间较长，其OS/PFS较好（HR分别为0.76，95%置信区间0.56-1.02，p=0.064和HR为0.74，95%置信区间0.55-0.99，p=0.042）。
我们的研究表明，mHSPC接受ADT的持续时间与接受ARSI治疗的mCRPC患者的生存显著相关。这些发现提示前列腺肿瘤的初始管理与mCRPC更好的预后之间可能存在联系。有必要进行前瞻性试验。
