Prostate specific membrane antigen positron emission tomography (PSMA-PET) has a high detection rate and influences therapeutic decision making in prostate cancer (PCa) patients with biochemical recurrence or persistence after primary prostatectomy. However, the outcome of PET-based salvage radiotherapy (sRT) in terms of metastasis-free survival (MFS) has not yet been extensively studied. MFS is associated with a significant risk of death from PCa and is a surrogate parameter for PCa specific survival. The purpose of this analysis was to assess MFS in the era of PSMA PET/CT which was used for sRT guidance and for restaging in terms of biochemical failure after sRT. Additionally the metastatic pattern on PSMA PET images after sRT was evaluated.
This multicenter (7 centers from 4 countries), retrospective analysis included patients referred for PSMA PET/CT after radical prostatectomy due to biochemically recurrent or persistent disease. Patients with distant metastases (lymph nodes above iliac bifurcation, bone/visceral metastases) in PSMA PET/CT prior to sRT were excluded. MFS was the primary study endpoint. Cox-regression analysis was performed to assess the impact of clinical parameters derived from the MSKCC nomogram as well as of positive findings in pre-sRT PET (recurrent disease in the prostatic fossa / positive lymph nodes in the pelvis) on MFS. Finally, the localization of the metastases in PSMA PET/CT after sRT was assessed.
The final analysis included 502 patients. Nearly all patients (n=481, 96%) received intensity-modulated RT with a median dose of 70 Gy to the prostatic fossa. In case of PET positive lymph nodes (n=198, 39%), elective pelvic lymphatics were irradiated with a dose of 45-50 Gy including a boost to the PET positive regions (up to 60 Gy) in most of the cases. Androgen deprivation therapy was given in 160 (32%) patients. After a medium follow-up time of 40 months (IQR: 27-49), 187 (37.3%) and 113 (22.5%) patients had biochemical recurrent disease and distant metastatic disease, respectively. The 2- and 4-year MFS rates after sRT were 86% and 74%, respectively. In multivariate analysis PSA before sRT, pT stage, local recurrences in PET and pelvic lymph nodes in PET had significant (p<0.05) impact on MFS. The metastases after sRT were localized in subdiaphragmal paraaortic lymph nodes (44%), pelvic bones (23%), non-pelvic bones (19%), supradiaphragmal lymph nodes (9%) and visceral organs (5%).
This analysis on MFS showed promising results in terms of tumor control. Additionally, the present analysis confirmed the strong prognostic effect on MFS of known variables (e.g. PSA level prior to sRT) but also depicted the prognostic impact of PET-derived variables (local recurrences and pelvic lymph nodes metastases). Most of the metastases after sRT were located in abdominal lymph nodes.