The Champalimaud Centre for the Unknown, Lisbon, Portugal.
The Champalimaud Centre for the Unknown, Lisbon, Portugal.
Radiother Oncol. 2022 Apr;169:35-42. doi: 10.1016/j.radonc.2022.02.016. Epub 2022 Feb 18.
The present study explores PSA density (PSA-D) as predictor of biochemical and local failure in organ-confined prostate cancer at 3-6 months after hypofractionated stereotactic ablative radiotherapy (SABR).
A cohort of 219, hormone-naïve, NCCN intermediate-risk prostate cancer patients were derived from a phase 2 study of 5 × 9 Gy prostate cancer SABR. PSA-D was calculated at 3 and 6 months by dividing serum PSA by the MR-derived prostate CTV, while the slope of the 3-6 months curve was used to express the kinetics of PSA-D decay.
The median follow-up was 60.3 (range 46-76) months, and the actuarial 7-year bRFS was 98.0% for intermediate-risk favorable (FIR) patients versus 84.5% for the unfavorable (UIR) subgroup (P = 0.02). Fourteen patients developed a Phoenix-defined biochemical PSA relapse (bRFS) at a median of 34.2 months, 11 confirmed with Ga-PSMA PET/CT scan that revealed tracer uptake at the site of dominant intraprostatic pretreatment lesion in 8 patients. The 3-month PSA-D concertation (cut-off 0.08 ng/ml) and 3-6 months decay slope (cut-off -0.45) values were predictive of long-term bRFS. A dual adverse PSA-D permutation was detected in 25/148 UIR patients, exhibiting 47.5% 7-year bRFS compared with 94.1% for the remaining 123 UIR patients with favorable PSA-D kinetics (P = 0.0006). Intraprostatic local relapse in patients with a 3-month PSA-D > 0.080 ng/ml was 11.0% vs. 1.7% for patients with PSA-D ≤ 0.080 ng/ml (P = 0.01) and 2.3% vs. 4.3%, respectively, for nodal progression (P = 0.68).
Early post-treatment PSA-D kinetics transcends pre-treatment risk stratification of tumor relapse and adds a nuance in the biological characterization of intermediate-risk prostate cancer phenotypes. The dual adverse PSA-D algorithm may serve as a tool to validate current search of classifiers of radioresistance in prostate cancer with therapeutic implications.
本研究探讨了前列腺特异性抗原密度（PSA-D）在接受低分割立体定向消融放疗（SABR）后 3-6 个月时对局限性前列腺癌生化和局部失败的预测作用。
从一项 5×9Gy 前列腺 SABR 的 2 期研究中，我们得到了 219 名激素初治、NCCN 中危前列腺癌患者的队列。通过将血清 PSA 除以 MRI 得出的前列腺CTV，计算 PSA-D 在 3 个月和 6 个月时的值，而 PSA-D 衰减的 3-6 个月曲线斜率则用于表达 PSA-D 衰减的动力学。
中位随访时间为 60.3 个月（范围为 46-76），中危有利（FIR）患者的 7 年生化无复发生存率（bRFS）为 98.0%，而不利（UIR）亚组为 84.5%（P=0.02）。14 名患者在中位时间 34.2 个月时出现了 Phoenix 定义的生化 PSA 复发（bRFS），其中 11 名经 Ga-PSMA PET/CT 扫描证实，在 8 名患者中发现了在治疗前主导的前列腺内病变部位有示踪剂摄取。3 个月时 PSA-D 浓度（截断值为 0.08ng/ml）和 3-6 个月时的衰减斜率（截断值为-0.45）值可预测长期 bRFS。在 148 名 UIR 患者中检测到 25 例双不良 PSA-D 排列，与其余 123 例具有良好 PSA-D 动力学的 UIR 患者（7 年 bRFS 为 94.1%）相比，7 年 bRFS 为 47.5%（P=0.0006）。在 3 个月 PSA-D＞0.080ng/ml 的患者中，局部前列腺内复发率为 11.0%，而 PSA-D≤0.080ng/ml 的患者为 1.7%（P=0.01），淋巴结进展的发生率分别为 2.3%和 4.3%（P=0.68）。
治疗后早期 PSA-D 动力学超越了肿瘤复发的术前风险分层，并为中危前列腺癌表型的生物学特征提供了细微差别。双不良 PSA-D 算法可能成为验证当前具有治疗意义的前列腺癌放射抵抗分类器搜索的工具。
