Tsuboi Ichiro, Matsukawa Akihiro, Kardoust Parizi Mehdi, Klemm Jakob, Mancon Stefano, Chiujdea Sever, Fazekas Tamás, Miszczyk Marcin, Laukhtina Ekaterina, Kawada Tatsushi, Katayama Satoshi, Iwata Takehiro, Bekku Kensuke, Karakiewicz Pierre, Wada Koichiro, Rouprêt Morgan, Araki Motoo, Shariat Shahrokh F
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Shimane University Faculty of Medicine, Shimane, Japan; Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Department of Urology, Jikei University School of Medicine, Tokyo, Japan.
Eur Urol Oncol. 2024 Dec;7(6):1185-1194. doi: 10.1016/j.euo.2024.03.007. Epub 2024 Apr 4.
It remains unclear to what extent the therapy of the primary local tumor, such as radical prostatectomy (RP) and radiation therapy (RT), improves overall survival in patients with low-volume metastatic hormone-sensitive prostate cancer (mHSPC). However, data suggest a benefit of these therapies in preventing local events secondary to local tumor progression.
To evaluate the efficacy of adding local therapy (RP or RT) to systemic therapies, including androgen deprivation therapy, docetaxel, and/or androgen receptor axis-targeted agents, in preventing local events in mHSPC patients compared with systemic therapy alone (ie, without RT of the prostate or RP).
Three databases and meeting abstracts were queried in November 2023 for studies analyzing mHSPC patients treated with local therapy. The primary outcome of interest was the prevention of overall local events (urinary tract infection, urinary tract obstruction, and gross hematuria) due to local disease progression. Subgroup analyses were conducted to assess the differential outcomes according to the type of local therapy (RP or RT).
Overall, six studies, comprising two randomized controlled trials, were included for a systematic review and meta-analysis. The overall incidence of local events was significantly lower in the local treatment plus systemic therapy group than in the systemic therapy only groups (relative risk [RR]: 0.50, 95% confidence interval [CI]: 0.28-0.88, p = 0.016). RP significantly reduced the incidence of overall local events (RR: 0.24, 95% CI: 0.11-0.52) and that of local events requiring surgical intervention (RR: 0.08, 95% CI: 0.03-0.25). Although there was no statistically significant difference between the RT plus systemic therapy and systemic therapy only groups in terms of overall local events, the incidence of local events requiring surgical intervention was significantly lower in the RT plus systemic therapy group (RR: 0.70, 95% CI: 0.49-0.99); local events requiring surgical intervention of the upper urinary tract was significantly lower in local treatment groups (RR: 0.60, 95% CI: 0.37-0.98, p = 0.04). However, a subgroup analysis revealed that neither RP nor RT significantly impacted the prevention of local events requiring surgical intervention of the upper urinary tract.
In some patients with mHSPC, RP or RT of primary tumor seems to reduce the incidence of local progression and events requiring surgical intervention. Identifying which patients are most likely to benefit from local therapy, and at what time point (eg, after response of metastases), will be necessary to set up a study assessing the risk, benefits, and alternatives to therapy of the primary tumor in the mHSPC setting.
Our study suggests that local therapy of the prostate, such as radical prostatectomy or radiotherapy, in patients with metastatic hormone-sensitive prostate cancer can prevent local events, such as urinary obstruction and gross hematuria.
目前尚不清楚原发性局部肿瘤的治疗，如根治性前列腺切除术（RP）和放射治疗（RT），在低容量转移性激素敏感性前列腺癌（mHSPC）患者中能在多大程度上提高总体生存率。然而，数据表明这些治疗在预防局部肿瘤进展继发的局部事件方面有好处。
评估在全身治疗（包括雄激素剥夺治疗、多西他赛和/或雄激素受体轴靶向药物）基础上加用局部治疗（RP或RT），与单纯全身治疗（即不进行前列腺RT或RP）相比，在预防mHSPC患者局部事件方面的疗效。
2023年11月查询了三个数据库和会议摘要，以获取分析接受局部治疗的mHSPC患者的研究。感兴趣的主要结局是预防因局部疾病进展导致的总体局部事件（尿路感染、尿路梗阻和肉眼血尿）。进行亚组分析以评估根据局部治疗类型（RP或RT）的不同结局。
总体而言，纳入了六项研究，包括两项随机对照试验，进行系统评价和荟萃分析。局部治疗加全身治疗组的局部事件总体发生率显著低于单纯全身治疗组（相对风险[RR]：0.50，95%置信区间[CI]：0.28 - 0.88，p = 0.016）。RP显著降低了总体局部事件的发生率（RR：0.24，95% CI：0.11 - 0.52）以及需要手术干预的局部事件的发生率（RR：0.08，95% CI：0.03 - 0.25）。虽然RT加全身治疗组和单纯全身治疗组在总体局部事件方面无统计学显著差异，但RT加全身治疗组中需要手术干预的局部事件发生率显著更低（RR：0.70，95% CI：0.49 - 0.99）；局部治疗组中需要对上尿路进行手术干预的局部事件显著更低（RR：0.60，95% CI：0.37 - 0.98，p = 0.04）。然而，亚组分析显示，RP和RT均未对预防需要对上尿路进行手术干预的局部事件产生显著影响。
在一些mHSPC患者中，原发性肿瘤的RP或RT似乎可降低局部进展和需要手术干预的事件的发生率。确定哪些患者最有可能从局部治疗中获益以及在什么时间点（例如转移灶出现反应后），对于开展一项评估mHSPC环境中原发性肿瘤治疗的风险、益处和替代方案的研究是必要的。
我们的研究表明，转移性激素敏感性前列腺癌患者的前列腺局部治疗，如根治性前列腺切除术或放射治疗，可以预防局部事件，如尿路梗阻和肉眼血尿。
