Outcomes in Locally Advanced Non-Metastatic Prostate Cancer Presenting with Low PSA at Diagnosis.

Abstract

Men with low serum prostate-specific antigen (PSA) and high Gleason grade group (GGG) are thought to have poor outcomes compared to high PSA secretors. However, there is limited outcome data to support this. We report clinical outcomes from a single-institutional cohort of men presenting with locally advanced prostate cancer but low serum PSA. Data from electronic database of a UK tertiary cancer center was acquired for men with histological diagnosis of prostate adenocarcinoma, GGG 4 or 5, stage ≥cT3a, and PSA <10ug/L at diagnosis. Men with metastatic disease, or prior androgen deprivation therapy (ADT) were excluded. Biochemical progression was defined as per Phoenix criteria (PSA > nadir+2) for primary radiotherapy, or PSA >0.2 ug/L after primary prostatectomy (and post-operative radiotherapy, if received). Overall survival (OS, from date of diagnosis to death), metastasis-free survival (MFS, from diagnosis to first recorded metastasis or death), and biochemical progression free survival (bPFS, from diagnosis to biochemical progression or death) were estimated by Kaplan Meier method, and multivariable analysis performed using Cox proportional hazards method. Medical records of 7,200 men presenting with non-metastatic prostate cancer from 2013 to 2021 were screened, of which 270 men satisfying the eligibility criteria were included for this study. Initial analysis of 123 men shows median PSA at presentation 7.1 ug/L (IQR 5.6-8.5), and median age 70 years (IQR 65-75). Histology was GGG 4 in 47.6% and 5 in 52.4%. Tumor stage was cT3a in 56.6%, cT3b in 36.9%, and T4 in 6.6%. Pelvic nodes were involved in 5% patients. Majority (83.7%) were treated with radical radiotherapy (external beam alone 64.2%, brachytherapy boost 19.5%), with 24 months ADT; 11.4% underwent radical prostatectomy, and 4.9% received ADT alone. Three men (2.4%) received docetaxel, and one received abiraterone. At a median follow up of 66 months (IQR 27-77), 36 (29.3%) patients had biochemical failure. Total 23 (18.6%) patients had metastases at recurrence, which were visceral in 4%, bone-only in 10%, and nodal-only in 4%. Total 38 (30.6%) patients had died, 23% with prostate cancer and 11% due to other causes. Five-year bPFS was 65.9%, MFS 69.0%, and OS was 77.4%. GGG 5 (versus 4) was associated with significantly worse 5-year bPFS (59.4% vs 73.9%, HR 1.8, 95% CI 1.0-3.2, p = 0.05) and MFS (59.2% vs 81.6%, HR 2.2, 1.2-4.2, p = 0.02). On multivariable analysis including age and PSA at diagnosis, only GGG 5 was associated with worse bPFS (HR 1.8, 1.0-3.3, p = 0.05) and MFS (HR 2.42, 1.25-4.67, p = 0.009). Men with low secreting but high Gleason grade group prostate cancer are a relatively rare group with poor clinical outcomes despite being non-metastatic. Ongoing work (expected completion June 2023) will analyze remaining cases, and compare outcomes within an expanded multicentric cohort with matched controls having elevated PSA at presentation.