The VISION and TheraP trials introduced different PET-based criteria for patient selection for treatment with ¹⁷⁷Lu-PSMA-617 (LuPSMA). TheraP used a higher prostate-specific membrane antigen (PSMA) uptake threshold than VISION and required ¹⁸F-FDG PET to exclude patients with discordant findings. Although the screen-failed patients had shorter overall survival (OS) than those treated with LuPSMA, it remains unclear whether their outcomes might have been modified if they had been exposed to LuPSMA. In this study, we evaluated associations between the TheraP eligibility criteria and subgroups and the treatment outcomes of patients who were deemed suitable and treated on the basis of VISION criteria. Methods: Consecutive patients who were treated with LuPSMA and who underwent pretreatment PSMA and ¹⁸F-FDG PET were classified as TheraP-eligible (TheraP-E) and TheraP-ineligible (TheraP-I), the latter of which were subclassified as low PSMA or discordant. Odds ratios for an at least 50% decline in prostate-specific antigen (PSA50) were computed using logistic regression, and hazard ratios (HRs) for PSA progression-free survival (PSA-PFS) and OS were computed using Cox regressions. Multivariable analyses were adjusted for baseline imaging and clinical parameters. Results: Of 75 patients, 31 (41%) were deemed TheraP-I; of those, 24 were subclassified as having discordant disease. TheraP-I patients had a lower PSA50 rate than that of TheraP-E patients (28% vs. 67%; odds ratio, 0.19; 95% CI, 0.06–0.52; P = 0.002) and a higher risk of PSA progression (HR, 2.0; 95% CI, 1.2–3.3; P = 0.007). OS in the TheraP-I group was numerically shorter than in the TheraP-E group, but the comparison was only marginally significant (10.4 mo vs. not reached; HR, 1.9; 95% CI, 1.0–3.7; P = 0.054). TheraP-I patients with low PSMA had no significantly different risk of death (P = 0.9) from that of TheraP-E patients, but those with discordant findings had higher risk of death (HR, 2.3; 95% CI, 1.1–4.6; P = 0.02). Discordant disease remained prognostic for OS after adjusting for baseline imaging and clinical parameters (HR, 3.0; 95% CI, 1.3–6.8; P = 0.01). Conclusion: In VISION-eligible patients who were treated with LuPSMA, TheraP-I patients with discordant findings had lower PSA50, PSA-PFS, and OS. Our study suggests that the shorter OS of TheraP-I patients is mainly driven by the presence of discordant disease.

VISION 和 TheraP 试验引入了不同的基于 PET 的标准，用于选择接受 ¹⁷⁷Lu-PSMA-617 （LuPSMA） 治疗的患者。TheraP 使用比 VISION 更高的前列腺特异性膜抗原 （PSMA） 摄取阈值，并且需要 ¹⁸F-FDG PET 来排除结果不一致的患者。尽管筛查失败的患者总生存期 （OS） 短于接受 LuPSMA 治疗的患者，但尚不清楚如果他们暴露于 LuPSMA，他们的结局是否会改变。在这项研究中，我们评估了 TheraP 资格标准和亚组之间的关联，以及被认为合适并根据 VISION 标准接受治疗的患者的治疗结果。方法：接受 LuPSMA 治疗并接受治疗前 PSMA 和 ¹⁸例 F-FDG PET 的连续患者被归类为 TheraP 合格 （TheraP-E） 和 TheraP 不合格 （TheraP-I），后者被细分为低 PSMA 或不和谐。使用 logistic 回归计算前列腺特异性抗原 （PSA50） 下降至少 50% 的比值比，使用 Cox 回归计算 PSA 无进展生存期 （PSA-PFS） 和 OS 的风险比 （HR）。根据基线成像和临床参数调整多变量分析。结果：在 75 名患者中，31 名 （41%） 被认为是 TheraP-I;其中，24 例被亚分类为患有不一致的疾病。TheraP-I 患者的 PSA50 率低于 TheraP-E 患者（28% 对 67%;比值比，0.19;95% CI，0.06-0.52;P = 0.002）和 PSA 进展风险较高 （HR， 2.0;95% CI， 1.2-3.3;P = 0.007）。 TheraP-I 组的 OS 在数值上短于 TheraP-E 组，但比较仅略微显著（10.4 个月与未达到;心率，1.9;95% CI，1.0–3.7;P = 0.054）。PSMA 低的 TheraP-I 患者的死亡风险 （P = 0.9） 与 TheraP-E 患者没有显著差异，但结果不一致的患者死亡风险更高 （HR，2.3;95% CI，1.1-4.6;P = 0.02）。在调整基线影像学和临床参数后，不一致的疾病仍然对 OS 预后有预后 （HR，3.0;95% CI，1.3-6.8;P = 0.01）。结论：在接受 LuPSMA 治疗的符合 VISION 条件的患者中，结果不一致的 TheraP-I 患者的 PSA50 、 PSA-PFS 和 OS 较低。我们的研究表明，TheraP-I 患者较短的 OS 主要是由不一致疾病的存在驱动的。