Prostate cancer patients who face recurrence after radical prostatectomy (RP) have better overall survival (OS) rates with a combination of salvage radiation therapy (RT) and 24 months of anti-androgen therapy (AAT) than with RT alone, according to research presented at the American Society for Radiation Oncology’s (ASTRO’s) 57th Annual Meeting.

Many men with prostate cancer who undergo RP—surgical removal of the prostate— experience recurrence, as evidenced by an elevated prostate specific antigen (PSA) level.

These patients are then often given salvage RT to the prostate tumour bed.

Androgens are male hormones that can stimulate the growth of prostate cancer cells, therefore, peripheral androgen blockage, or AAT, can be used to decrease or suppress the amount of androgens in the body in combination with salvage RT to possibly improve patient survival in this setting.

RTOG 9601 was a large phase III double-blinded, placebo-controlled trial that evaluated if long-term AAT, when combined with salvage RT, would improve OS and other cancer control outcomes for prostate cancer patients who had failed RP.

Conducted from 1998 to 2003, the study included 761 prostate cancer patients from centres across the U.S. and Canada and compared a salvage regimen of only RT to one of RT plus AAT.

The study group included patients had undergone a RP—and had, or had developed elevated prostate specific antigen (PSA) levels from 0.2 to 4.0 ng/ml with prostate tumours classified as either T2pN0 and a positive surgical margin (indicating the tumour was confined to the prostate with no lymph nodes affected) or T3pN0 (indicating the tumour had grown outside of the prostate, but no lymph nodes were affected).

The patients were randomly assigned to receive either RT of 64.6 Gy in 36 fractions of 1.8 Gy plus 24 months of AAT therapy of 150 mg of daily bicalutamide during and after RT; or to receive the RT regimen plus a placebo.

A total of 384 patients were assigned to the RT plus AAT group, and 377 patients were assigned to the RT plus placebo group.

With a median follow-up of 12.6 years, the study results showed that the actuarial OS at 10 years was 82 percent for the RT plus AAT patients and 78 percent for the RT plus placebo patients; with a hazard ratio of 0.75 (95 percent CI: 0.58-0.98) with a two-sided p-value = 0.036.

Data indicated that the addition of AAT decreased the rate of death by prostate cancer and decreased the risk of the cancer metastasising (spreading to other parts of the body).

The 12-year incidence of prostate cancer central-reviewed deaths was 2.3 percent for the RT plus AAT group, compared to 7.5 percent for the RT plus placebo group (p<0.001).

At 12 years, the cancer had metastasised in 51 patients (14 percent) in the RT plus AAT group, compared to 83 patients (23 percent) in the RT plus placebo group (p<0.001).

Additionally, late grade 3 and grade 4 bladder and bowel side effects were similar in both groups, whereas 70 percent of men in the RT plus AAT group reported swelling of the breasts, compared to 11 percent from the RT plus placebo group.

“Over the last 25 years, many men with intermediate risk prostate cancer have undergone RP, yet many will face recurrence in one to four years with a rising PSA,” said lead study author William U. Shipley, MD, FACR, FASTRO, Andres Soriano Distinguished Professor of Radiation Oncology at the Massachusetts General Hospital and the Harvard Medical School.

“Our results show that salvage RT plus androgen blockage, when compared to RT with a placebo, improved long-term overall survival and reduced death from prostate cancer without adding significantly to radiation toxicity. Because prostate cancer progresses slowly, follow-up of over 12 years was necessary to demonstrate a statistically better patient survival with combined AAT and RT therapy. Further statistical analyses, which are underway, may identify subgroups of prostate cancer patients who may not benefit from hormone therapy added to salvage RT, and others for whom it may be especially beneficial.”

Source: ASTRO