Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Cristian Lolli, Giuseppe Schepisi, Aldo Rosano, Guido Giordano, Marianna Garofoli, Vincenzo Emanuele Chiuri, Lucia Fratino, Elisa Zanardi, Luca Galli, Francesco Massari, Ugo Falagario, Pasquale Rescigno, Giuseppe Fornarini, Francesca Sanguedolce, Daniele Santini, Giuseppe Procopio, Orazio Caffo, Giuseppe Carrieri, Matteo Landriscina, Ugo De Giorgi
{"title":"局部/局部晚期疾病的初始治疗方法对于指导转移性耐受性前列腺癌的治疗至关重要。","authors":"Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Cristian Lolli, Giuseppe Schepisi, Aldo Rosano, Guido Giordano, Marianna Garofoli, Vincenzo Emanuele Chiuri, Lucia Fratino, Elisa Zanardi, Luca Galli, Francesco Massari, Ugo Falagario, Pasquale Rescigno, Giuseppe Fornarini, Francesca Sanguedolce, Daniele Santini, Giuseppe Procopio, Orazio Caffo, Giuseppe Carrieri, Matteo Landriscina, Ugo De Giorgi","doi":"10.1038/s41391-024-00800-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20727,"journal":{"name":"Prostate Cancer and Prostatic Diseases","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care.\",\"authors\":\"Vincenza Conteduca, Piergiorgio Di Tullio, Rossana Allamprese, Giuseppina Bruno, Cristian Lolli, Giuseppe Schepisi, Aldo Rosano, Guido Giordano, Marianna Garofoli, Vincenzo Emanuele Chiuri, Lucia Fratino, Elisa Zanardi, Luca Galli, Francesco Massari, Ugo Falagario, Pasquale Rescigno, Giuseppe Fornarini, Francesca Sanguedolce, Daniele Santini, Giuseppe Procopio, Orazio Caffo, Giuseppe Carrieri, Matteo Landriscina, Ugo De Giorgi\",\"doi\":\"10.1038/s41391-024-00800-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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. 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引用次数: 0
摘要
背景：目前，有多种疗法可用于治疗转移性抗性前列腺癌（mCRPC），但没有特定的临床因素可用于个性化治疗。我们首先研究了接受雄激素受体信号抑制剂（ARSI）治疗的激素敏感性前列腺癌（HSPC）患者的雄激素剥夺治疗（ADT）持续时间对预后的影响：对2011年7月至2021年10月期间开始接受ARSI治疗的mCRPC患者进行了多中心队列研究。根据他们的初始疾病负担和ADT治疗HSPC的持续时间，将原发性进展（PP）男性患者分为四组：低/中风险局部疾病（LOC）、高风险局部/局部晚期疾病（LAD）和短期（ST）：我们共纳入了 919 名 mCRPC 患者，中位年龄为 77 岁[四分位数间距 (IQR) = 71-82)]。HSPC患者的中位ADT持续时间为24个月（IQR=14-40）。中位随访时间为91个月（IQR = 62-138），自ARSI开始的中位OS和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 中（n = 655，71.3%），LOC 和 LAD 与 ST ADT 相比，LT ADT 的死亡风险几乎翻了一番（LOC/ST：危险比 [HR] = 2.01；95% CI 1.54-2.64；LAD/ST：HR = 1.73；95% CI 1.34-2.24；p 2（HR = 1.55；95% CI 1.06-2.26；p = 0.03）。PFS的结果也类似。此外，在有DN mHSPC病史的患者（n = 264，28.7%）中，长期服用CRPC可获得更好的OS/PFS（分别为HR = 0.76，95% CI 0.56-1.02，p = 0.064和HR = 0.74，95% CI 0.55-0.99，p = 0.042）：我们的研究表明，mHSPC的ADT持续时间与接受ARSI治疗的mCRPC的生存率显著相关。这些研究结果表明，前列腺肿瘤的初始治疗与mCRPC更好的预后之间可能存在联系。有必要进行前瞻性试验。
Initial management approach for localized/locally advanced disease is critical to guide metastatic castration-resistant prostate cancer care.
Background: 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.
Methods: 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.
Results: 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).
Conclusions: 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.
期刊介绍：
Prostate Cancer and Prostatic Diseases covers all aspects of prostatic diseases, in particular prostate cancer, the subject of intensive basic and clinical research world-wide. The journal also reports on exciting new developments being made in diagnosis, surgery, radiotherapy, drug discovery and medical management.
Prostate Cancer and Prostatic Diseases is of interest to surgeons, oncologists and clinicians treating patients and to those involved in research into diseases of the prostate. The journal covers the three main areas - prostate cancer, male LUTS and prostatitis.
Prostate Cancer and Prostatic Diseases publishes original research articles, reviews, topical comment and critical appraisals of scientific meetings and the latest books. The journal also contains a calendar of forthcoming scientific meetings. The Editors and a distinguished Editorial Board ensure that submitted articles receive fast and efficient attention and are refereed to the highest possible scientific standard. A fast track system is available for topical articles of particular significance.
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