Aggressive Therapy Boosts Survival in Localized Cancer

ANAHEIM, California—The outcome of patients with clinically localized prostate cancer can be improved with aggressive treatment, according to two large studies presented at the American Urological Association annual meeting.

"Localized prostate cancer is often indolent, and there are no randomized trials comparing conservative management to radical prostatectomy and radiotherapy," said Mani Menon, MD, of the Josephine Ford Cancer Center, Detroit. His study (abstract 621) involved a cohort of 3,159 men younger than 76 years with clinically localized prostate cancer diagnosed between 1980 and 1997.

"The idea that there is no survival advantage with definitive treatment was resoundingly defeated by this analysis," Dr. Menon said.

The study was a restricted cohort analysis, which mimics randomization in that "all patients are eligible for any treatment, and it adjusts for baseline variables," Dr. Menon said. The study sought to determine whether long-term survival was different between patients who were managed conservatively and patients who were treated definitively with either radiotherapy or radical prostatectomy. Mean follow-up was 6 years (range up to 19 years).

At the time of analysis, 2,288 patients (68%) were still alive. One third of the men who died succumbed to prostate cancer. Conservative treatment was selected for 1,297 patients, radical prostatectomy for 963, and radiotherapy for 899. Hormonal therapy was given to 30% of patients in the "watchful waiting" group, 8% of patients undergoing prostatectomy, and 8% of patients undergoing radiotherapy.

Survival Rates

The overall adjusted survival rates at 15 years were 35% for conservative management, 50% for radiotherapy, and 65% for radical prostatectomy. The corresponding prostate-cancer-specific survival rates were 79%, 87%, and 92%, respectively, he said.

While patients managed conservatively were indeed older and sicker, as would be expected, these tumors were also less aggressive and of lower grade.

The study controlled for these and other confounding factors (comorbidity by Charlson score, age, grade of tumor, income status, and year of diagnosis) and still found that patients undergoing radiotherapy or prostatectomy had a lower overall mortality than patients managed conservatively.

The relative risk for overall mortality was 0.42 for prostatectomy and 0.68 for radiotherapy (P < .001). The relative risk for cancer-specific mortality was 0.37 for prostatectomy (P < .0001) and 0.62 for radiotherapy (P < .001). In addition to treatment, tumor grade and year of diagnosis were also important factors in outcome, he noted.

Radical prostatectomy decreased cancer-specific mortality by 59% and increased survival by 8.6 years. Radiotherapy decreased cancer-specific mortality by 38% and increased survival by 4.6 years, Dr. Menon said. He predicted that current radiotherapy techniques would probably improve survival to an even greater degree.

High-Risk Patients

Another study reported at the AUA meeting (abstract 620) suggested that patients with unfavorable localized prostate cancer with intermediate- to high-risk factors might benefit from external beam radiation and ultrasound-guided brachytherapy. Such therapy enhanced the long-term biochemical outcome among 236 patients followed for up to 13 years.

Haakon Ragde, MD, clinical professor of urology, University of Virginia, reported on the study, which was conducted at the University of Washington, where he formerly worked.

Patients were diagnosed between 1987 and 1995, and received 45 Gy delivered to the prostate and a limited pelvic field, followed by transperineal brachytherapy to the prostate at a minimum peripheral dose of 120 Gy for iodine-125 seeds or 90 Gy for palladium-103 seeds.

Patients were judged to have intermediate to high risk of locally advanced disease because of a clinical stage of T2b or greater, PSA level more than 10 ng/mL, and/or Gleason score of 6 or higher. Biochemical failure was defined as three consecutive increases in PSA level from a nadir level, spaced at least 3 months apart.

At baseline, the average age was 70 years, and average pretreatment PSA was 15.3 ng/mL; 63% had biopsy Gleason score 6 or higher, 60% had clinical stage at least T2b, and 53% had a PSA over 10 ng/mL.

Overall survival in this group was 63.5%. As of last follow-up (median follow-up of 86.5 months), 75% of patients were clinically and biochemically disease-free, Dr. Ragde reported.

Biochemical disease-free survival was 83% at 3 years, 77% at 5 years, 75% at 10 years, and 74% at 13 years. Last PSA measurement was less than 0.2 ng/mL in 80% of patients, and less than 0.5 in 90%.

"The long-term disease-free survival of 75% suggests that external beam radiation and brachytherapy may be an effective treatment for clinically localized prostate cancer with intermediate- to high-risk prognostic variables," Dr. Ragde said.