177Lu-PSMA-617 radioligand therapy (177Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of177Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at177Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of177Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon68Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the177Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of177Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent177Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with177Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients.
目前，转移性去势抵抗性前列腺癌（mCRPC）患者接受¹⁷⁷Lu-PSMA-617放射性配体治疗（¹⁷⁷Lu-PSMA-RLT）的方案通常为4–6个周期，每周期给药6.0–7.4 GBq，间隔6–8周。尽管在较大规模的前瞻性试验中已证实，无论开始¹⁷⁷Lu-PSMA-RLT时的肿瘤负荷如何，该疗法均具有安全性和有效性，但对于早期响应、寡转移的mCRPC患者，由于肿瘤“沉没效应”减弱导致肾脏吸收剂量增加，带来了治疗难题。由于担心可能失去疾病控制，目前尚未常规采用响应适应、剂量分配、间歇性治疗（最多六个周期）的策略。本研究对19例早期响应、寡转移肿瘤负荷的患者，在完成2个（四分位距2–3）周期¹⁷⁷Lu-PSMA-RLT（每周期6.5 ± 0.7 GBq）后暂停治疗，待基于⁶⁸Ga-PSMA-11 PET/CT的疾病进展（依据PCWG3标准）时恢复治疗。若后续能实现基于PSMA的影像学响应，则再次实施治疗间歇。患者总共接受了5个（四分位距3–6）周期治疗，累积活度为32 ± 11 GBq。在整个¹⁷⁷Lu-PSMA-RLT及随访期间，定期进行包括血常规、肝肾功能在内的常规血液检查，并依据CTCAE v5.0标准进行毒性分级。生存结局采用Kaplan-Meier法计算。总体而言，实现了累计9个月（四分位距6–17）的无治疗期，¹⁷⁷Lu-PSMA-RLT治疗周期跨越了16个月（四分位距9–22）。15例（84%）患者在首次治疗间歇后对后续周期治疗有响应，其中7/19例（37%）患者的间歇性¹⁷⁷Lu-PSMA-RLT包含≥2次治疗间歇。中位无进展生存期为27个月（95% CI: 23–31），总生存期为45个月（95% CI: 28–62）。在45 ± 21个月的随访期间，未观察到≥3级的血液学或肾脏毒性。肾脏累积平均吸收剂量为16.7 ± 8.3 Gy，单位活度剂量为0.53 ± 0.21 Gy/GBq。对于早期响应的寡转移疾病患者，采用¹⁷⁷Lu-PSMA-617进行间歇性放射性配体治疗是可行的。后续治疗周期后疾病进展出现较晚，且未出现显著毒性，这为在特定患者中进一步研究间歇性治疗理念提供了依据。
肿瘤(癌症)患者之家