Incidence of local prostate cancer recurrence by 68Ga-PSMA-11 PET/CT is higher after definitive Radiation Therapy than after Radical Prostatectomy: a single center post-hoc retrospective analysis of recurrence patterns of 787 patients.

Background: 20 to 50% of patients with prostate cancer (PCa) undergoing radical prostatectomy (RP) or definitive radiation therapy (dRT) will experience disease recurrence. However, anatomical recurrence patterns may differ depending on the therapeutic approaches. The aim of this post-hoc retrospective analysis was to investigate if the relapse pattern as assessed by 68Ga-PSMA-11 PET/CT was different depending on the type of local pelvic therapy (RP, dRT, salvage RT (SRT), pelvic lymph node dissection (PLND), pelvic lymph node RT (PLNRT)) in patients with non-metastatic castrate sensitive (nmCS) recurrent disease after primary definitive therapy.

Methods: Patients who underwent a 68Ga-PSMA-11 PET/CT for nmCS PCa recurrent disease after primary definitive therapy were screened from a database of 4 prospective studies (NCT02940262, NCT03515577, NCT04050215, NCT03582774). Patients who underwent primary staging (n=95), or who did not undergo any definitive therapy (n=68), or with known metastatic disease (M1) (n=68) or with castrate resistant (CR) disease (n=291) were excluded. We examined the relationship between recurrence patterns as assessed by 68Ga-PSMA-11 PET/CT (PROMISE criteria) and the prior local treatments: i) RP, ii) RP + PLND; iii) dRT iv) dRT + PLNRT v) RP + SRT.

Results: 787 patients were included in the analysis. Median PSA levels before the scan were 0.50 (0.02-72.5) ng/ml, 4.40 (0.1-202) ng/ml, and 1.07 (0.04-33) ng/ml for patients who underwent RP (n=464), dRT (n=109); and post-RP SRT (n=214), respectively. Median time from initial therapy to first recurrence was 27.7 months after RP and 54.6 months after dRT (Whitney-Mann U, p=<0.00001). Patients who underwent RP had a lower local recurrence (LR) rate (T+) by PSMA PET than those with dRT (99/464; 21.3% vs 69/109; 63.3%; Chi² p= <0.00001). Furthermore, the extrapelvic metastasis (M1) (93/464; 20.0% vs 51/109; 46.8%; Chi² p= <0.00001) and overall detection rates (279/464; 60.1% vs 102/109; 93.6%; Chi² p= <0.00001) were lower for RP than dRT. The positivity rate of pelvic nodal disease (N1) by 68Ga-PSMA-11 PET/CT was similar between patients who underwent RP with or without PLND (150/379; 39.6% vs. 29/85; 34.1%; Chi² p=0.35). Rate of N1 disease did not differ among patients who underwent dRT with PLNRT (9/19; 47.4%) and those without PLNRT (34/90; 37.8%; Chi² p= 0.44). Median time from post-RP SRT to second recurrence was 22.3 months. In patients who had a second recurrence after RP and SRT the positivity rate of LR (T+), N1 disease and M1 disease by PSMA PET/CT was 11.7% (24/214), 46% (99/214) and 44% (95/214), respectively.

Conclusions: In this cohort of patients with nmCS PCa recurrent disease after primary definitive therapy, the rate of local recurrence as assessed by 68Ga-PSMA-11 PET/CT is higher after dRT than after RP. However, in this cohort median time to recurrence was significantly longer for patients who underwent dRT. Pelvic lymph node treatments, by RT or surgery, did not significantly alter pelvic lymph node recurrence rates as assessed by 68Ga-PSMA-11 PET/CT.