A significant proportion of men develop prostate-specific antigen (PSA) failure after radical prostatectomy (RP) inspite of improved detection and surgical techniques for early prostate cancer. The recurrences are usually detected by elevated PSA levels alone. However, there is no clarity on whether the increased PSA levels are due to local recurrence or distant metastasis. Patients with local recurrence might benefit with salvage radiation therapy (SRT) whereas salvage hormone therapy (SHT) is beneficial in patients with metastasis. A recent phase 3 trial reported improved survival outcomes with early intervention of SHT in PSA relapsed patients after definitive therapy.
The study evaluates the efficacy of SRT + SHT as compared to SHT alone in patients with PSA failure after RP.
- Multicenter, randomized, open-label phase 3 clinical trial
- Confirmed diagnosis of localized prostate cancer treated by RP
- PSA concentrations had reduced to <0.1 ng/ml after RP, and then increased to 0.4-1.0 ng/ml
- Serum PSA level between 0.4 to 1 ng/ml at study entry
- ECOG PS 0 – 1
- The SHT group (n=105) received 80 mg bicalutamide (BCL) – the dose approved in Japan, followed by luteinizing hormone-releasing hormone agonist in case of BCL failure)
- SRT ± SHT group (n=105) were treated with 64.8 Gy of SRT followed by the same regimen as in the SHT group in case of SRT failure
- Cohort was followed up for a median period of 5.5 years
- Time to treatment failure (TTF) of BCL defined as the time from randomization to treatment failure of BCL or censoring at the date of last follow-up
- TTF of protocol treatment
- Overall survival (OS)
- Clinical relapse-free survival (RFS)
- Adverse events
- Patient reported quality of life (QoL) outcomes
- The SRT ± SHT group had a significantly longer TTF to BCL (8.6 years vs 5.6 years; hazard ratio 0.56, 95% confidence interval: 0.38 – 0.82; one-sided p = 0.001).
- Comparison of survival outcomes is shown in figure 1.
- Thirty-two of 102 patients (31%) in the SRT ± SHT group did not have SRT treatment failure.
- Erectile dysfunction was the most frequent grade 3-4 adverse event with an incidence of 80% in the SHT group vs. 74% in the SRT ± SHT group
- Initial salvage radiation therapy (SRT) prior to salvage hormone therapy (SHT) is beneficial in patients with prostate-specific antigen failure after radical prostatectomy.
- SRT along with SHT prolongs the time to treatment failure of bicalutamide in such patients as compared to SHT alone.
Eur Urol. 2020 Jun;77(6):689-698. Doi: 10.1016/j.eururo.2019.11.023.