- Email: [email protected]
A multi-institutional matched-control analysis of adjuvant and salvage postoperative radiation therapy for pT3-4N0 prostate cancer
686
J.A. Smith / Urologic Oncology: Seminars and Original Investigations 26 (2008) 680 – 691
risk for a need for salvage therapy and a higher rate of anastomotic strictures. As they pointed out, these unfavorable outcomes decrease with increasing surgical volume. In fact, the rate of anastomotic stricture is less than 1% in the hands of experienced robotic surgeons and most are able to achieve positive margin rates comparable or superior to an open approach once adequate experience has been attained. Thus, it is difficult to extrapolate much of the information in this manuscript to a contemporary setting. doi:10.1016/j.urolonc.2008.09.013 Joseph A. Smith, M.D. A multi-institutional matched-control analysis of adjuvant and salvage postoperative radiation therapy for pT3-4N0 prostate cancer. Trabulsi EJ, Valicenti RK, Hanlon AL, Pisansky TM, Sandler HM, Kuban DA, Catton CN, Michalski JM, Zelefsky MJ, Kupelian PA, Lin DW, Anscher MS, Slawin KM, Roehrborn CG, Forman JD, Liauw SL, Kestin LL, Deweese TL, Scardino PT, Stephenson AJ, Pollack A, Departments of, Department of Urology, Fox Chase Cancer Center, Philadelphia, PA. Urology 2008;July 29 [Epub ahead of print] Objectives: It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure. Methods: Using a multi-institutional database of 2,299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery. Results: A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] ⫽ 1.6, P ⫽ 0.049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR ⫽ 2.3, log ratio [LR] P ⫽ 0.0007). From the end of RT, SRT, and Gleason score ⱖ 8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score ⱖ 8 was a significant predictor of FFBF. Conclusions: Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score ⱖ 8 was the only factor on multivariate analysis associated with metastatic progression. Commentary Randomized studies have shown convincingly the benefit of adjuvant radiation vs. no radiation or delayed radiation after radical prostatectomy. Improved disease-free survival and, recently, overall survival have been demonstrated. What is still uncertain, though, is whether adjuvant radiation provides improved outcomes compared with early (at the first sign of PSA relapse) salvage therapy. This study compared adjuvant with salvage therapy but the median PSA before salvage therapy was 0.7 ng/ml with a range of 0.2 to 2 ng/ml. This nonrandomized study helps confirm the findings of the randomized trials but still does not answer the question of whether adjuvant is better than early salvage therapy. doi:10.1016/j.urolonc.2008.09.014 Joseph A. Smith, M.D.
LABORATORY RESEARCH Integrative genomics analysis reveals silencing of -adrenergic signaling by polycomb in prostate cancer. Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM, Department of Pathology, Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI. Cancer Cell 2007;12:419 –31 The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, -2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes. Commentary EZH2 is a member of the Polycomb group of transcriptional repressors, which specifically methylates lysine 27 of histone H3. EZH2 is associated with aggressive epithelial tumors, and its expression correlates with poor prognosis. However, the genes targeted for silencing by EZH2
J.A. Smith / Urologic Oncology: Seminars and Original Investigations 26 (2008) 680 – 691
risk for a need for salvage therapy and a higher rate of anastomotic strictures. As they pointed out, these unfavorable outcomes decrease with increasing surgical volume. In fact, the rate of anastomotic stricture is less than 1% in the hands of experienced robotic surgeons and most are able to achieve positive margin rates comparable or superior to an open approach once adequate experience has been attained. Thus, it is difficult to extrapolate much of the information in this manuscript to a contemporary setting. doi:10.1016/j.urolonc.2008.09.013 Joseph A. Smith, M.D. A multi-institutional matched-control analysis of adjuvant and salvage postoperative radiation therapy for pT3-4N0 prostate cancer. Trabulsi EJ, Valicenti RK, Hanlon AL, Pisansky TM, Sandler HM, Kuban DA, Catton CN, Michalski JM, Zelefsky MJ, Kupelian PA, Lin DW, Anscher MS, Slawin KM, Roehrborn CG, Forman JD, Liauw SL, Kestin LL, Deweese TL, Scardino PT, Stephenson AJ, Pollack A, Departments of, Department of Urology, Fox Chase Cancer Center, Philadelphia, PA. Urology 2008;July 29 [Epub ahead of print] Objectives: It is unclear whether postoperative salvage radiation therapy (SRT) and early adjuvant radiotherapy (ART) after radical prostatectomy lead to equivalent long-term tumor control. We studied a group of patients undergoing ART by comparing them with a matched control group undergoing SRT after biochemical failure. Methods: Using a multi-institutional database of 2,299 patients, 449 patients with pT3-4N0 disease were eligible for inclusion, including 211 patients receiving ART and 238 patients receiving SRT. Patients were matched in a 1:1 ratio according to preoperative prostate-specific antigen Gleason score, seminal vesicle invasion, surgical margin status, and follow-up from date of surgery. Results: A total of 192 patients were matched (96:96). The median follow-up was 94 months from surgery and 73 months from RT completion. There was a significant reduction in biochemical failure with ART compared with SRT. The 5-year freedom from biochemical failure (FFBF) from surgery was 75% after ART, compared with 66% for SRT (hazard ratio [HR] ⫽ 1.6, P ⫽ 0.049). The 5-year FFBF from the end of RT was 73% after ART, compared with 50% after SRT (HR ⫽ 2.3, log ratio [LR] P ⫽ 0.0007). From the end of RT, SRT, and Gleason score ⱖ 8 were independent predictors of diminished FFBF. From the date of surgery, Gleason score ⱖ 8 was a significant predictor of FFBF. Conclusions: Early ART for pT3-4N0 prostate cancer significantly reduces the risk of long-term biochemical progression after radical prostatectomy compared with SRT. Gleason score ⱖ 8 was the only factor on multivariate analysis associated with metastatic progression. Commentary Randomized studies have shown convincingly the benefit of adjuvant radiation vs. no radiation or delayed radiation after radical prostatectomy. Improved disease-free survival and, recently, overall survival have been demonstrated. What is still uncertain, though, is whether adjuvant radiation provides improved outcomes compared with early (at the first sign of PSA relapse) salvage therapy. This study compared adjuvant with salvage therapy but the median PSA before salvage therapy was 0.7 ng/ml with a range of 0.2 to 2 ng/ml. This nonrandomized study helps confirm the findings of the randomized trials but still does not answer the question of whether adjuvant is better than early salvage therapy. doi:10.1016/j.urolonc.2008.09.014 Joseph A. Smith, M.D.
LABORATORY RESEARCH Integrative genomics analysis reveals silencing of -adrenergic signaling by polycomb in prostate cancer. Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM, Department of Pathology, Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI. Cancer Cell 2007;12:419 –31 The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, -2), a critical mediator of beta-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes. Commentary EZH2 is a member of the Polycomb group of transcriptional repressors, which specifically methylates lysine 27 of histone H3. EZH2 is associated with aggressive epithelial tumors, and its expression correlates with poor prognosis. However, the genes targeted for silencing by EZH2