Dr. Roach

San Francisco—The long-standing debate over radical prostatectomy versus radiation therapy for unfavorable-risk prostate cancer has not gone away. But if the recent Prostate Cancer Symposium reflects broader professional opinions, the surgery camp and the radiation camp are moving toward combination treatments. There are no definitive prospective randomized trials, but evidence of a consensus that prostatectomy plus radiation therapy may offer the best patient outcomes is emerging.

"I don't really know what the best treatment is for unfavorable-risk cancers," said long-time radiation therapy advocate Mack Roach III, MD, director of clinical research in radiation oncology at the University of California, San Francisco. "We know that radical prostatectomy alone is not the most favorable treatment. We know that radiation alone is not ideal. Radical prostatectomy plus radiation may prove to be the best treatment."

Dr. Montie

Dr. Roach's call for combination therapy was shared by James Montie, MD, professor and chairman of urology at the University of Michigan Health Systems, Ann Arbor. Earlier detection has created a growing population of men with apparently localized but large-volume prostate cancer that is potentially lethal because tumors are large, Dr. Montie pointed out. However, long-term surgical outcomes are poor for men with relatively large, localized tumors because positive margins are common and the incidence of morbidities such as incontinence and erectile dysfunction may be higher.

Data support combination Tx

The combination of high rates of recurrence and morbidity has led physicians to see radical prostatectomy as most appropriate for men with smaller tumors who are more likely to be cured by surgery without significant functional impairment.

"Those who need treatment the least are considered the ideal patients for radical prostatectomy," Dr. Montie said. "Patients with large, localized tumors who need treatment the most are the least likely to get surgery. If the primary tumor is not completely eliminated, prognosis may be poor regardless of the systemic treatment used. What may be best is surgery to reduce tumor volume and radiation to kill disease at the periphery."

Case series analysis of radical prostatectomy in selected patients with unfavorable-risk disease have shown 10-year disease-specific survival up to 90%, Dr. Montie noted. In most cases, some combination of surgery plus radiation therapy, androgen deprivation therapy, and chemotherapy has produced the longest survival and, possibly, the fewest local side effects.

The relative success of combination therapy should not be a surprise, Dr. Montie added. Large colon, breast, and other cancers typically respond better to combination treatment than to any single modality. Radiation, cytotoxic drugs, and other therapies are almost always more effective with smaller tumor volumes than with large masses, he said.

"The data suggest that you can salvage patients who have positive margins after RP with post-op radiation," Dr. Roach said. "But only if you hit the target. If surgery is done, we should be giving hormone therapy and radiation, and we should use marker seeds to identify the target area."

Recent UCSF studies using metallic gold markers implanted during surgery found that external beam radiation therapy misses the target field in 28% of cases.

The most effective strategy may be radical prostatectomy plus radiation therapy delivered to the entire pelvic region, Dr. Roach said. There is a wide distribution of lymph nodes throughout the region, he explained, and microscopic metastases can easily turn localized disease into regional disease within a few years of surgery. Pelvic-wide radiation can significantly delay recurrence, effectively turning a lethal disease into a chronic condition.

"The primary endpoint may need to be quality of life in short-term studies," Dr. Montie concluded. "We must critically look at complication rates and side effects in addition to survival. We want patients alive, but not wishing they were dead due to incontinence that is difficult to treat."