Demirci Ridvan Arda, Ghodsi Alireza, Gulati Roman, Behnia Sanaz, Nelson Peter S, Cheng Heather H, Yezefski Todd A, Haffner Michael C, Hawley Jessica E, Montgomery Robert B, Yu Evan Y, Schweizer Michael T, Chen Delphine L, Iravani Amir
Department of Radiology, University of Washington, Seattle, Washington.
Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.
J Nucl Med. 2025 Jan 3;66(1):47-53. doi: 10.2967/jnumed.124.268167.
The VISION and TheraP trials introduced different PET-based criteria for patient selection for treatment with Lu-PSMA-617 (LuPSMA). TheraP used a higher prostate-specific membrane antigen (PSMA) uptake threshold than VISION and required F-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. Consecutive patients who were treated with LuPSMA and who underwent pretreatment PSMA and F-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. 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; = 0.002) and a higher risk of PSA progression (HR, 2.0; 95% CI, 1.2-3.3; = 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; = 0.054). TheraP-I patients with low PSMA had no significantly different risk of death ( = 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; = 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; = 0.01). 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试验和TheraP试验引入了不同的基于PET的标准，用于选择接受镥-PSMA-617（LuPSMA）治疗的患者。TheraP使用的前列腺特异性膜抗原（PSMA）摄取阈值高于VISION，并且需要F-FDG PET来排除有不一致结果的患者。尽管筛查未通过的患者总生存期（OS）比接受LuPSMA治疗的患者短，但仍不清楚如果他们接受LuPSMA治疗，其结局是否会有所改善。在本研究中，我们评估了TheraP入选标准及亚组与根据VISION标准被认为适合并接受治疗的患者的治疗结局之间的关联。连续接受LuPSMA治疗且接受过治疗前PSMA和F-FDG PET检查的患者被分类为符合TheraP标准（TheraP-E）和不符合TheraP标准（TheraP-I），后者又被细分为低PSMA或不一致。使用逻辑回归计算前列腺特异性抗原至少下降50%（PSA50）的优势比，并使用Cox回归计算PSA无进展生存期（PSA-PFS）和OS的风险比（HR）。多变量分析针对基线影像学和临床参数进行了调整。在75例患者中，31例（41%）被认为不符合TheraP标准；其中，24例被细分为患有不一致疾病。不符合TheraP标准的患者的PSA50率低于符合TheraP标准的患者（28%对67%；优势比，0.19；95%CI，0.06 - 0.52；P = 0.002），且PSA进展风险更高（HR，2.0；95%CI，1.2 - 3.3；P = 0.007）。不符合TheraP标准组的OS在数值上短于符合TheraP标准组，但比较仅具有边缘显著性（10.4个月对未达到；HR，1.9；95%CI，1.0 - 3.7；P = 0.054）。PSMA低的不符合TheraP标准的患者与符合TheraP标准的患者的死亡风险无显著差异（P = 0.9），但有不一致结果的患者死亡风险更高（HR，2.3；95%CI，1.1 - 4.6；P = 0.02）。在针对基线影像学和临床参数进行调整后，不一致疾病仍然是OS的预后因素（HR，3.0；95%CI，1.3 - 6.8；P = 0.01）。在接受LuPSMA治疗的符合VISION标准的患者中，有不一致结果的不符合TheraP标准的患者的PSA50、PSA-PFS和OS更低。我们的研究表明，不符合TheraP标准的患者较短的OS主要是由不一致疾病的存在所致。
