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PSA Trends and Clinical Outcomes Following Radiotherapy Combined with Androgen Deprivation Therapy for Prostate Cancer: A Single-Centre Retrospective Cohort Study from Saudi Arabia

Year: 2026

Type: preprint

Abstract: Background Combined external-beam radiotherapy and androgen deprivation therapy (ADT) is standard treatment for men with intermediate- to high-risk prostate cancer, but outcome data from the Gulf region remain limited despite a rising regional disease burden. We evaluated longitudinal PSA response, treatment-related morbidity, and oncological outcomes in patients treated with curative-intent radiotherapy plus ADT, characterising PSA kinetics over the first nine months of treatment and identifying clinical predictors of the PSA trajectory. Methods In this retrospective cohort study at King Abdulaziz Medical City, Riyadh, we included all adult patients with prostate cancer who received radiotherapy combined with ADT and had complete treatment and follow-up records. Demographic, clinical, and treatment data were extracted from electronic medical records, with serial PSA recorded at baseline and at 3, 6, and 9 months. Changes in PSA from baseline were assessed with the paired Wilcoxon signed-rank test, and a linear mixed-effects model (random intercept per patient; fixed effects for time, age, Gleason group, and metastatic status; PSA log₁₀[PSA + 1]-transformed) was used to identify predictors of longitudinal PSA levels. Results Seventy-four patients were included (median age 68.0 years, IQR: 63.0–75.0; median PSA at diagnosis 17.3 ng/mL, IQR: 9.3–33.0), 64.9% with Gleason group 4–5 disease. Most received hypofractionated radiotherapy (median 60 Gy in 20 fractions) with a single ADT cycle (90.4%), predominantly leuprolide (91.8%). PSA fell progressively at every interval (all p < 0.001): median reductions of 91.9%, 99.2%, and 99.7% from baseline at 3, 6, and 9 months, with the proportion achieving a ≥ 50% reduction rising from 73.2% to 93.0% over the same period; median PSA nadir was 0.028 ng/mL (IQR: 0.024–0.560). On adjusted mixed-effects modelling, reductions at each time point remained significant independent of age and Gleason group (β = −0.81 to − 1.13 versus baseline, all p < 0.001), while metastatic disease at presentation predicted higher longitudinal PSA levels. Disease recurrence occurred in 5.4% of patients, with a median time to recurrence of 68.5 months; treatment-related toxicity was low, with urinary incontinence and erectile dysfunction each affecting fewer than 7% of patients at 12 months. Conclusions In this predominantly high-risk, real-world cohort, combined radiotherapy and ADT produced rapid, deep, and durable PSA suppression with low toxicity and low biochemical recurrence, irrespective of baseline Gleason grade. These findings support the effectiveness and tolerability of this regimen outside the trial setting and provide PSA kinetic benchmarks from an underrepresented population that may complement randomised evidence, though prospective data incorporating PSMA-PET-based surveillance are needed to confirm whether early deep response translates into durable survival benefit.

Source: Research Square

DOI: 10.21203/rs.3.rs-11131060/v1