PHILADELPHIA -- For Medicare-age prostate cancer patients, action extends survival better than observation, according to investigators here.
PHILADELPHIA, Dec. 13 -- For Medicare-age prostate cancer patients, action extends survival better than observation, according to investigators here.
In a 12-year study evaluating data for 44,630 men, ages 65 to 80, with low- and intermediate-risk prostate cancer, treated men had a 31% lower risk of death during the next 12 years than men followed by watchful waiting, found Yu-Ning Wong, M.D., of the Fox Chase Cancer Center here, and colleagues. The investigators included neither urologists nor radiologists.
Men given a radical prostatectomy or radiation therapy had longer five- and 10-year rates for disease-specific and overall survival than men followed by observation, they reported in the Dec. 13 issue of the Journal of the American Medical Association.
The men, diagnosed from 1991 to 1999 with organ-confined well- or moderately differentiated disease, were followed until death or the end of the study on Dec. 31, 2002. Data came from Medicare's Surveillance, Epidemiology and End Results (SEER) database.
Of the patients, 32,022 were classified as having received treatment if they had claims for radical prostatectomy or radiation therapy during the first six months after diagnosis. The observation group included 12,608 patients without treatment claims.
Patients who received only hormonal therapy were excluded because the effect of oral antiandrogen agents on overall survival in men with localized prostate cancer is likely to be small, the researchers said.
After using propensity scores to adjust for potential confounders (tumor characteristics, demographics, and comorbidities), the researchers reported a statistically significant survival advantage associated with treatment (hazard ratio, 0.69; 95% confidence interval, 0.66-0.72).
At the end of the 12-year study, 4,663 men (37%) in the observational, group and 7,639 men (23.8%) in the treatment group had died (P
However, they added that "because observational data can never be free of concerns about selection bias and confounding, these results must be validated by rigorous randomized controlled trials of elderly men with localized prostate cancer before the findings can be used to inform treatment decisions."
Dr. Wong reported serving on a health outcomes advisory board for Sanofi Aventis and has applied for grant funding from Sanofi Aventis. Co-author J. Sanford Schwartz, M.D., reported that he serves on a health outcomes advisory board for Sanofi Aventis and has applied for grant funding from the firm.
In an accompanying editorial, Mark Litwin, M.D., MPH, and David Miller, M.D. MPH, of the University of California Los Angeles said that Dr. Wong and colleagues addressed an important gap in current knowledge about survival in older men with a "well-designed and well-executed" observational study.
Nevertheless, they said, reasoned interpretation of the study requires consideration of the absolute survival outcomes. Dr. Wong and colleagues found that prostate cancer was responsible for fewer than 10% of deaths in both the observation (6.8%) and the treatment (8%) cohorts. "Many more men die with prostate cancer than of it," they said.
Residual confounding remains an important issue they said. "As with any observational study, the potential for residual bias and confounding remains," they noted. "In particular, despite the authors' earnest attempts to balance the cohorts, unmeasured differences may persist. For instance, even with established methods for comorbidity adjustment, claims-based analyses fully characterize neither the nature and severity of concurrent medical conditions nor the general impression of life expectancy that is typically cultivated by clinicians at the time of treatment choice. Most urologists and radiation oncologists will attest that older men who receive active treatment are inherently different from those managed expectantly."
They also pointed out that side effects of therapy must be taken into account. "In many clinical scenarios, a survival benefit alone provides ample rationale for the widespread application of a therapeutic intervention," they wrote." Among older men with early-stage prostate cancer, however, a more nuanced risk-benefit assessment must consider the adverse consequences of local therapy, including the potential for treatment-related complications and impairments in health-related quality of life."
Improvement in the quality of care for men with prostate cancer may best be achieved not by treating more patients but by treating them more discerningly. "Clinicians must remain steadfast in their efforts to reduce overtreatment and undertreatment by thoughtfully defining each patient's unique balance between the natural history of the disease and that individual patient's life expectancy," they wrote.
The association reported in this study will be confirmed or refuted by the results of ongoing randomized controlled trials, Drs. Litwin and Miller said. "Until then, physicians should apply these provocative finding.
Dr Litwin has served as a principal member of a steering committee that is advisory to the principal investigator of Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) study, which is funded by an award to the University of California from TAP Pharmaceuticals. He has also received a stipend for serving as a scientific advisor to junior investigators associated with the CaPSURE study whose researchers are not directed by TAP. He was recently under contract with Amgen to lead an investigation of long-term bone fracture outcomes for which he received a stipend for conducting and writing the study.
Dr Litwin is under contract with Sanofi-Aventis for serving on the steering committee of Outcomes and Urology researchers overseeing a study of benign prostatic hyperplasia.