Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is becoming standard of care for men with biochemical recurrence (BCR) of prostate cancer. The implications of a negative PSMA PET/CT scan in this population remain unclear. This study aims to assess the outcome of patients with BCR post radical prostatectomy (RP) who have negative [18F]DCFPyL PET/CT scan at relapse. This is a post-hoc subgroup analysis of a prospective non randomized clinical trial. One hundred and one patients (median age, 75 years) with BCR after RP, who tested negative on [18F]DCFPyL PET/CT and subsequently either underwent salvage radiotherapy (sRT) with or without androgen deprivation therapy (ADT) or were followed without active treatment, were included. Freedom from progression (FFP) after negative PSMA PET/CT was determined based on follow-up imaging selected as per clinical practice. Uni- and multivariate Cox regression analyses were performed to examine the association of patients' characteristics, tumor-specific variables, and treatment with clinical progression at the last follow-up. FFP at 1-, 2-, and 3-year were reported using Kaplan Meier analysis. The median PSA level at PET/CT was 0.56 ng/mL (range, 0.4–11.3). Sixty five (64%) patients were followed without receiving further treatment, and 36 (36%) received sRT (18% to the prostate bed only and 18% to the prostate bed and pelvic lymph nodes) within 3 months of the PSMA PET. Seventeen of the sRT patients (17 of 36, 47%) received concomitant androgen deprivation therapy (ADT). Median follow-up was 39 months. Subsequent clinical progression was detected in 21 patients (21%), with 52% in pelvic lymph nodes, 52% in the prostatic fossa, 19% in distant lymph nodes, 14% in lungs, and 10% in bones. The FFP was 95% (95% CI: 91%-99%) at 12 months, 87% (95% CI: 81%-94%) at 24 months, and 79% (95% CI: 71%-88%) at 36 months. Multivariate Cox regression analysis revealed that an initial International Society of Urological Pathology (ISUP) grade 5 was significantly associated with clinical progression at the last follow-up (hazard ratio, 5.1, P value, 0.04). Furthermore, the receipt of sRT correlated significantly with lower clinical progression at the last follow-up (hazard ratio, 0.2, P value, 0.03), whereas other clinical and tumor-specific parameters did not. Following surveillance-only and sRT, 29% (19 of 65) and 6% (2 of 36) of patients, respectively, showed clinical progression. In the sRT group, no significant difference was observed in FFP between patients who underwent sRT to the prostatic fossa versus those who received sRT to the prostatic fossa and pelvic lymph nodes, although the numbers in these groups were small. This study suggests that salvage radiotherapy is associated with a decreased or delayed clinical progression in patients with biochemical recurrence following radical prostatectomy who have negative PSMA PET/CT scan results. The analysis also underscores the prognostic significance of the initial ISUP grade, with ISUP grade 5 being associated with worse outcomes. Registered September 14, 2016; NCT02899312 .

中文翻译：

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PSMA PET/CT 阴性对前列腺癌生化复发的预后意义


前列腺特异性膜抗原 (PSMA) 正电子发射断层扫描/计算机断层扫描 (PET/CT) 正在成为前列腺癌生化复发 (BCR) 男性的标准治疗方法。 PSMA PET/CT 扫描阴性对这一人群的影响仍不清楚。本研究旨在评估根治性前列腺切除术 (RP) 后复发时 [18F]DCFPyL PET/CT 扫描阴性的 BCR 患者的结果。这是一项前瞻性非随机临床试验的事后亚组分析。 101 名 RP 后出现 BCR 的患者（中位年龄 75 岁），[18F]DCFPyL PET/CT 检测呈阴性，随后接受挽救性放疗 (sRT) 联合或不联合雄激素剥夺疗法 (ADT)，或随访时不进行雄激素剥夺疗法 (ADT)。积极治疗，包括在内。 PSMA PET/CT 阴性后的无进展 (FFP) 是根据根据临床实践选择的后续影像学确定的。进行单变量和多变量 Cox 回归分析，以检查患者特征、肿瘤特异性变量以及治疗与最后一次随访时临床进展的关联。使用 Kaplan Meier 分析报告 1 年、2 年和 3 年的 FFP。 PET/CT 的中位 PSA 水平为 0.56 ng/mL（范围：0.4-11.3）。 65 名 (64%) 患者在未接受进一步治疗的情况下进行随访，36 名 (36%) 患者在 PSMA PET 后 3 个月内接受了 sRT（18% 仅接受前列腺床治疗，18% 接受前列腺床和盆腔淋巴结治疗）。 17 名 sRT 患者（36 名患者中的 17 名，47%）接受了伴随的雄激素剥夺治疗 (ADT)。中位随访时间为 39 个月。 21 名患者 (21%) 检测到随后的临床进展，其中 52% 发生在盆腔淋巴结，52% 发生在前列腺窝，19% 发生在远处淋巴结，14% 发生在肺部，10% 发生在骨骼。 12 个月时 FFP 为 95%（95% CI：91%-99%），24 个月时为 87%（95% CI：81%-94%），79%（95% CI：71%-88%） ）36 个月时。多变量 Cox 回归分析显示，初始国际泌尿病理学会 (ISUP) 5 级与最后一次随访时的临床进展显着相关（风险比，5.1，P 值，0.04）。此外，接受 sRT 与最后一次随访时较低的临床进展显着相关（风险比为 0.2，P 值为 0.03），而其他临床和肿瘤特异性参数则不然。仅监测和 sRT 后，分别有 29%（65 名患者中的 19 名）和 6%（36 名患者中的 2 名）出现临床进展。在 sRT 组中，接受前列腺窝 sRT 的患者与接受前列腺窝和盆腔淋巴结 sRT 的患者之间的 FFP 没有观察到显着差异，尽管这些组中的人数较少。这项研究表明，对于 PSMA PET/CT 扫描结果阴性、根治性前列腺切除术后生化复发的患者，挽救性放疗与临床进展减少或延迟相关。该分析还强调了初始 ISUP 等级的预后意义，ISUP 5 级与更差的结果相关。 2016年9月14日注册； NCT02899312。