Role for Androgen Withdrawal Prior to Radiation and Surgery for Prostate Cancer?

Androgen blockade has potential applications beyond late-stage metastaticcancer of the prostate, according to Nelson N. Stone, md, Professor ofUrology and Radiation Oncology at Mt. Sinai School of Medicine. Althoughandrogen withdrawal therapy (AWT) has been used effectively to prolongsurvival in patients with metastatic disease, its use in the neoadjuvantand adjuvant setting prior to surgery and radiation therapy (RT) representsa promising new area of investigation, Dr. Stone said at the 14th Symposiumof the Chemotherapy Foundation.

Dr. Stone cited a recent study that showed no significant differencein outcome between patients treated with radical prostatectomy and radiation.Thanks to prostate-specific antigen (PSA) testing following definitivetherapy, he added, it is now possible to identify the high number of patientswho fail local therapy.

"Upwards of 35% to 50% of men treated for cure will be found tohave a rising PSA within 5 years of treatment," Dr. Stone continued.For those patients, intermittent androgen withdrawal may result in a longertime to progression. Initial phase II studies of post-treatment intermittentAWT have been promising, and larger clinical trials are being planned.

Complete hormone therapy (CHT) has virtually replaced orchiectomy withor without oral estrogens. Combining the luteinizing hormone-releasinghormone (LHRH) agonist leuprolide (Lupron) with an oral antiandrogen, suchas flutamide (Eulexin) or the newer agent, biclutamide (Casodex), confersa 25% to 35% survival advantage over orchiectomy or leuprolide alone.

"Nonetheless," Dr. Stone said, "perhaps we can do betterwith the use of adjuvant hormonal therapy in conjunction with radiationor surgery." He described the use of AWT before radical prostatectomyor RT as exciting. According to Dr. Stone, 3 months of CHT prior to surgerywill shrink the tumor enough to result in a sixfold decrease in the likelihoodof encountering a positive surgical margin. "It remains to be seenwhether this will translate into improved survival," he said.

A recent Radiation Therapy Oncology Group study reported a 36% progression-freesurvival when 4 months of CHT preceded radiation, compared to 14% withradiation alone.

With RT, the issues are different, Dr. Stone explained. Four monthsof CHT will decrease the size of the prostate by about 40%. It has beenestablished that radiation works best when the tumor volume is minimal.It, in fact, allows the radiation dose to be minimized to contiguous structures.

Furthermore, there may be a synergistic effect on apoptosis when CHTprecedes radiation. A smaller prostate also has benefits for brachytherapyand makes imaging easier, he added.

Prostate cancer rates are expected to peak in the year 2000, Dr. Stonesaid making improved treatment strategies essential. Investigation of broaderapplications of AWT may well point the way, he concluded.