Is early adjuvant radiotherapy associated with different outcomes compared to delayed therapy?

The authors evaluated the optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer.

Radical  prostatectomy (surgery to remove the prostate) remains the most common treatment for localized prostate cancer (has not spread beyond the prostate) with proven long-term cancer control compared with other treatment options. However, up to one-third of men undergoing radical prostatectomy have locally advanced disease (cancer has spread through the wall of the prostate).  

Evidence has demonstrated that adjuvant radiation therapy (administered after surgery) lowers the risk of biochemical recurrence (rising prostate specific antigen levels following treatment) and distant metastases (spread of cancer) while improving overall survival. However, the optimal timing of adjuvant radiation therapy for maximal benefit remains unknown.

This study examined the outcomes of early compared to delayed adjuvant radiation therapy following radical prostatectomy for locally advanced prostate cancer.

Early adjuvant radiation therapy patients were administered radiation therapy less than 4 months following radical prostatectomy and were followed for an average of 5.8 years. Delayed adjuvant radiation therapy patients were administered adjuvant radiation therapy between 4 and 12 months after radical prostatectomy and followed for an average of 5.1 months.

The overall mortality rate (percentage of patients who died from any cause) was 18.6% for early adjuvant radiation patients and 15.2% for delayed adjuvant radiation patients. Prostate cancer-specific mortality (death from prostate cancer) rates were 2.6% for early adjuvant radiation patients and 3.9% for delayed adjuvant radiation therapy. 17.9% of early adjuvant radiation patients required salvage hormonal therapy (using hormones in medical therapy) and 24.4% of delayed adjuvant radiation patients. Rates of urethral stricture (abnormal narrowing of the tube that carries urine out of the body) were 24.8% for early adjuvant radiation patients and 17.1% for delayed adjuvant radiation patients.

Delaying adjuvant radiation therapy beyond 5 months was associated with 2.3 times the risk of prostate cancer-specific mortality, while delaying beyond 3 months was associated with a 60% increased risk of bone-related events. Delaying beyond 4 months was associated with 60% increased risk of requiring salvage hormonal therapy. However, administration beyond 9 months was associated with a 40% reduction in the risk of urethral strictures. There was a trend towards a 40% reduction in the risk of overall mortality associated with delaying adjuvant radiation therapy beyond 9 months, but this was not statistically significant.

The authors concluded that initiating adjuvant radiation therapy earlier than 5 months after radical prostatectomy for locally advanced prostate cancer is associated with improved prostate cancer-specific mortality, fewer bone-related events and less use of salvage hormonal therapy.