Re: Survival Among Men with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy or Radiation Therapy in the Prostate Specific Antigen Era: A. S. Kibel, J. P. Ciezki, E. A. Klein, C. A. Reddy, J. D. Lubahn, J. Haslag-Minoff, J. O. Deasy, J. M. Michalski, D. Kallogjeri, J. F. Piccirillo, D. M. Rabah, C. Yu, M. W. Kattan and A. J. StephensonJ Urol 2012; 187: 1259-1265.
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ABSTRACT: We assessed the effect of radical prostatectomy (RP) and external beam radiotherapy (EBRT) on distant metastases (DM) rates in patients with localized prostate cancer treated with RP or EBRT at a single specialized cancer center. Patients with clinical stages T1c-T3b prostate cancer were treated with intensity-modulated EBRT (> or = 81 Gy) or RP. Both cohorts included patients treated with salvage radiotherapy or androgen-deprivation therapy for biochemical failure. Salvage therapy for patients with RP was delivered a median of 13 months after biochemical failure compared with 69 months for EBRT patients. DM was compared controlling for patient age, clinical stage, serum prostate-specific antigen level, biopsy Gleason score, and year of treatment. The 8-year probability of freedom from metastatic progression was 97% for RP patients and 93% for EBRT patients. After adjustment for case mix, surgery was associated with a reduced risk of metastasis (hazard ratio, 0.35; 95% CI, 0.19 to 0.65; P < .001). Results were similar for prostate cancer-specific mortality (hazard ratio, 0.32; 95% CI, 0.13 to 0.80; P = .015). Rates of metastatic progression were similar for favorable-risk disease (1.9% difference in 8-year metastasis-free survival), somewhat reduced for intermediate-risk disease (3.3%), and more substantially reduced in unfavorable-risk disease (7.8% in 8-year metastatic progression). Metastatic progression is infrequent in men with low-risk prostate cancer treated with either RP or EBRT. RP patients with higher-risk disease treated had a lower risk of metastatic progression and prostate cancer-specific death than EBRT patients. These results may be confounded by differences in the use and timing of salvage therapy.Journal of Clinical Oncology 02/2010; 28(9):1508-13. DOI:10.1200/JCO.2009.22.2265 · 17.88 Impact Factor
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ABSTRACT: Because no adequate randomized trials have compared active treatment modalities for localized prostate cancer, the authors analyzed risk-adjusted, cancer-specific mortality outcomes among men who underwent radical prostatectomy, men who received external-beam radiation therapy, and men who received primary androgen-deprivation therapy. The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry comprises men from 40 urologic practice sites who are followed prospectively under uniform protocols, regardless of treatment. In the current study, 7538 men with localized disease were analyzed. Prostate cancer risk was assessed using the Kattan preoperative nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score, both well validated instruments that are calculated from clinical data at the time of diagnosis. A parametric survival model was constructed to compare outcomes across treatments adjusting for risk and age. In total, 266 men died of prostate cancer during follow-up. Adjusting for age and risk, the hazard ratio for cancer-specific mortality relative to prostatectomy was 2.21 (95% confidence interval [CI], 1.50-3.24) for radiation therapy and 3.22 (95% CI, 2.16-4.81) for androgen deprivation. Absolute differences between prostatectomy and radiation therapy were small for men at low risk but increased substantially for men at intermediate and high risk. These results were robust to a variety of different analytic techniques, including competing risks regression analysis, adjustment by CAPRA score rather than Kattan score, and examination of overall survival as the endpoint. Prostatectomy for localized prostate cancer was associated with a significant and substantial reduction in mortality relative to radiation therapy and androgen-deprivation monotherapy. Although this was not a randomized study, given the multiple adjustments and sensitivity analyses, it is unlikely that unmeasured confounding would account for the large observed differences in survival.Cancer 11/2010; 116(22):5226-34. DOI:10.1002/cncr.25456 · 4.90 Impact Factor
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ABSTRACT: It is not known whether short-term androgen-deprivation therapy (ADT) before and during radiotherapy improves cancer control and overall survival among patients with early, localized prostate adenocarcinoma. From 1994 through 2001, we randomly assigned 1979 eligible patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a prostate-specific antigen (PSA) level of 20 ng per milliliter or less to radiotherapy alone (992 patients) or radiotherapy with 4 months of total androgen suppression starting 2 months before radiotherapy (radiotherapy plus short-term ADT, 987 patients). The primary end point was overall survival. Secondary end points included disease-specific mortality, distant metastases, biochemical failure (an increasing level of PSA), and the rate of positive findings on repeat prostate biopsy at 2 years. The median follow-up period was 9.1 years. The 10-year rate of overall survival was 62% among patients receiving radiotherapy plus short-term ADT (the combined-therapy group), as compared with 57% among patients receiving radiotherapy alone (hazard ratio for death with radiotherapy alone, 1.17; P=0.03). The addition of short-term ADT was associated with a decrease in the 10-year disease-specific mortality from 8% to 4% (hazard ratio for radiotherapy alone, 1.87; P=0.001). Biochemical failure, distant metastases, and the rate of positive findings on repeat prostate biopsy at 2 years were significantly improved with radiotherapy plus short-term ADT. Acute and late radiation-induced toxic effects were similar in the two groups. The incidence of grade 3 or higher hormone-related toxic effects was less than 5%. Reanalysis according to risk showed reductions in overall and disease-specific mortality primarily among intermediate-risk patients, with no significant reductions among low-risk patients. Among patients with stage T1b, T1c, T2a, or T2b prostate adenocarcinoma and a PSA level of 20 ng per milliliter or less, the use of short-term ADT for 4 months before and during radiotherapy was associated with significantly decreased disease-specific mortality and increased overall survival. According to post hoc risk analysis, the benefit was mainly seen in intermediate-risk, but not low-risk, men. (Funded by the National Cancer Institute; RTOG 94-08 ClinicalTrials.gov number, NCT00002597.).New England Journal of Medicine 07/2011; 365(2):107-18. DOI:10.1056/NEJMoa1012348 · 54.42 Impact Factor