Introduction:

External beam radiotherapy (EBRT) is a curative treatment modality for localized prostate cancer, but 8–13% of patients treated with radiation and androgen deprivation therapy experience biochemical recurrence (BCR) at five years, as defined by the Phoenix criteria (PSA rise ≥ 2 ng/ml above the nadir). Concerns arise from the Phoenix criteria being based on conventionally fractionated EBRT while newer forms of radiation may have different PSA kinetics. Additionally, periodic PSA testing, while cost-effective, may not differentiate between local and distant recurrence, and conventional imaging has limitations in lower PSA ranges. PSMA-ligand PET/CT imaging has higher sensitivity and detection rates, even with PSA <0.5 ng/ml, increasing its role in BCR evaluation. This study aims to analyze PSMA-ligand PET/CT performance in patients with rising PSA post-radiotherapy comparing those above and below the Phoenix threshold.

Methods:

Retrospective review of PSMA-PET scans performed at our institution until 02/27/2023 was conducted to identify patients with initial BCR detected by PSMA-PET after RT. Primary outcome included lesion detection rate, defined as any positive finding on PSMA-PET. Local and oligometastatic recurrences were deemed potentially salvageable (suitable for focal salvage therapy). Detection rate and potential for salvage focal therapy were compared in patients with BCR above and below the phoenix threshold (≥ 2ng/ml above nadir) using chi-square. Frequencies and percentages were used to report categorical variables. Continuous data were described using mean and standard deviation or, alternatively, median and range/interquartile range. Statistical significance was set at p < 0.05.

Results:

45 patients with BCR after radiation (29 above phoenix threshold and 16 below) were assessed by PSMA-PET. Prebiopsy PSA and age at radiation were comparable in both groups. ADT was utilized after radiation in 51.7% of patients above the threshold and 62.5% below. Median PSA nadir was 0.31 above and 0.1 below threshold while PSA at PSMA-PET was 4 above and 1.2 below threshold. Primary outcome, lesion detection was comparable below and above phoenix threshold (14/16 (87.5%) vs 29/29 (100%); p=0.903). Furthermore, there was a significantly higher proportion of patients with disease potentially amenable to salvage therapy when the PSA was below the Phoenix threshold vs above (14/14 (100%) vs 22/29 (76.8%); p = 0.045. Post-PSMA treatments utilized included ADT (34.5% ≥2 and 31.3% <2), ARSI (10.3% ≥2 and 12.5% <2), chemotherapy (3.4% ≥2 and 6.3% <2), cryoablation/image-guided ablation (17.2% ≥2 and 18.8% <2), and metastasis-directed therapy (27.6% ≥2 and 25% <2).

Conclusion:

PSMA-PET demonstrates significant lesion detection capability even in patients with PSA levels below the Phoenix criteria for BCR. Lesions detected below the threshold can be identified by PSMA-PET, potentially allowing for focal salvage therapy to be administered before the disease progresses to polymetastasis. This emphasizes the utility of PSMA-PET in the early detection and management of recurrent prostate cancer, providing an opportunity for timely and targeted interventions.

Funding: N/A