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PSA After Salvage Radiation Therapy for Postprostatectomy Biochemical Recurrence Predicts Long-term Outcome Including Overall Survival
S132
International Journal of Radiation Oncology Biology Physics
301
Results: We identified 541 patients who received salvage RT, of whom 194 received ESRT and had pT3 and/or positive margins. One hundred eightyseven patients received ART for adverse pathologic features. Median follow-up from surgery was 7.0 and 8.9 years in the adjuvant and salvage cohorts, respectively. Median time from surgery to ART was 4.5 months; median time to first detectable PSA after prostatectomy in the salvage cohort was 23.7 months. Of ESRT patients, 3.4% received preoperative ADT, and 9.7% received concurrent ADT. After RT, median time to biochemical recurrence was 4.4 and 5.0 years in the ART and ESRT cohorts, respectively. On MVA, compared to ESRT, ART was associated with improved 10-year FFBF (73.9 vs 59.5%, HR Z 0.36, 95% CI: 0.23e0.58, P < .0001) and 10-year FFADT (91.2 vs 83.2%, HR Z 0.37, 95% CI: 0.18e0.76, P Z .007). There were no significant differences in FFDM (95.8 vs 91.8%, HR Z 0.58, 95% CI: 0.19e1.7, P Z .3), and OS (97.8 vs 95.2%, HR Z 1.24, 95% CI: 0.4e3.89, P Z .7). Matching reduced the median bias caused by differences in baseline characteristics of ESRT (n Z 176) and ART (n Z 169) patients from 24.4% to 3.5% for unmatched and matched groups, respectively. After PS matching, adjuvant RT remained significantly associated with improved FFBF (P < .0001) and FFADT (P Z .01). Conclusion: Postprostatectomy RT confers excellent long-term prostate cancer control, a finding validated by the long follow-up in this series. ART is associated with reduced risk of PSA recurrence and need for subsequent ADT compared to ESRT, although there were no statistically significant differences in freedom from distant metastases and OS. Optimal timing of postoperative RT further awaits the results of ongoing randomized trials. Author Disclosure: D. Buscariollo: None. R.H. Clayman: None. S. Galland: None. A.S. Feldman: None. D.M. Dahl: None. F.J. McGovern: None. A. Olumi: None. A. Eidelman: None. A. Niemierko: None. W.U. Shipley: Stock; Pfizer. A.L. Zietman: Editor; International Journal of Radiation Oncology * Biology * Physics. J.A. Efstathiou: Member; NRG Oncology GU Core Committee, Board of Directors Massachusetts Prostate Cancer Coalition. Co-Chair; NCI Bladder Task Force, NRG Comparative Effectiveness Committee. Chair; ASTRO Genitourinary Cancer Submission Tracks.
PSA After Salvage Radiation Therapy for Postprostatectomy Biochemical Recurrence Predicts Long-term Outcome Including Overall Survival T. Wiegel,1 D. Bartkowiak,1 R. Bottke,1 W. Hinkelbein,2 and A. Siegmann2; 1University Hospital Ulm, Ulm, Germany, 2Charite´ University Hospital Berlin, Berlin, Germany Purpose/Objective(s): For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiation therapy (SRT) is a second chance of cure. However, depending on pre-SRT risk factors, 40% to 70% of the patients experience further progression. Furthermore, the post-SRT level of prostate-specific antigen (PSA) is a prognostic marker. We report on the outcome of a cohort of patients who received SRT at 2 German centers. Materials/Methods: Between 1997 and 2011, 464 patients at 2 German centers, Berlin and Ulm, received SRT with 59.4 to 72 Gy (median, 66.6 Gy). All patient had 3-dimensional conformal treatment, including 60 cases with intensity modulated RT/volumetric modulated arc therapy technique. The median pre-SRT PSA was 0.31 ng/mL (interquartile range, 0.15e0.69). Post-SRT progression was defined as either PSA rising >0.2 ng/mL above nadir, or hormone treatment, or clinical recurrence. Data were analyzed with the Kaplan-Meier method (log-rank test) and with multivariate Cox regression. Results: The median follow-up was 5.9 years (maximum 14.4 years). In that time, 178 patients had recurrence and 30 men died. Univariate, a preRP PSA <10 ng/mL, pT<3, Gleason Score (GLS) <8, positive surgical margins R1, a pre-SRT PSA <0.2 ng/mL, and a post-SRT PSA <0.1 ng/ mL related with fewer and later second recurrences. In multivariable analysis, pT, GLS, R, and, most important, the pre-SRT PSA were significant covariates of progression. If the post-SRT PSA was included in the model, then failing the nadir was the most significant predictor of further progression. Achieving a post-SRT PSA <0.1 ng/mL correlated favorably with overall survival, in uni- and multivariable analysis. Conclusion: Early SRT initiated at a PSA <0.2 ng/mL correlates with achieving a post SRT <0.1 ng/mL. Such a response to SRT goes along with better freedom from progression and overall survival. Author Disclosure: T. Wiegel: None. D. Bartkowiak: None. R. Bottke: None. W. Hinkelbein: None. A. Siegmann: None.
302 Long-term Results of Early Salvage Versus Adjuvant Postprostatectomy Radiation: A Large Institutional Experience D. Buscariollo,1 R.H. Clayman,1 S. Galland,2 A.S. Feldman,1 D.M. Dahl,1 F.J. McGovern,1 A. Olumi,1 A. Eidelman,1 A. Niemierko,1 W.U. Shipley,1 A.L. Zietman,3 and J.A. Efstathiou3; 1Massachusetts General Hospital, Boston, MA, 2Bordeaux Hospital University, Bordeaux, Aquitaine, France, 3 Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Randomized trials and consensus statements support consideration of adjuvant radiation therapy (ART) after prostatectomy for adverse pathologic features (pT3, positive margins), although its use remains low. Whether early salvage radiation therapy (ESRT) is as effective as ART remains unknown. Materials/Methods: We performed a retrospective institutional analysis of 728 postprostatectomy patients receiving RT between 1993 and 2012. ESRT was defined as RT for biochemical recurrence with a postoperative prostate-specific antigen (PSA) level of 0.5 ng/mL. Outcomes examined were freedom from biochemical failure (FFBF), freedom from subsequent androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS). ART and ESRT were compared using multivariable analyses (MVA) with propensity score (PS) matching for preoperative PSA, age at the time of RT, pathologic Gleason score, pathologic T-stage, and margin status.
303 Dose Response for Salvage Radiation Therapy After Radical Prostatectomy in Margin-Positive Prostate Cancer S. Agrawal,1 T.M. Pisansky,2 D.A. Hamstra,3 S. Liauw,4 B.F. Koontz,5 J.A. Efstathiou,6 J.M. Michalski,7 F.Y. Feng,3 M.C. Abramowitz,8 A. Pollack,8 M.S. Anscher,9 D. Moghanaki,9 R.B. Den,10 K.L. Stephans,11 M. Kattan,11 A.J. Stephenson,11 and R.D. Tendulkar11; 1Case Western Reserve University School of Medicine, Cleveland, OH, 2Mayo Clinic, Rochester, MN, 3University of Michigan, Ann Arbor, MI, 4University of Chicago, Chicago, IL, 5Duke University Medical Center, Durham, NC, 6 Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7 Washington University School of Medicine, St. Louis, MO, 8University of Miami, Miami, FL, 9Virginia Commonwealth University Medical Center, Richmond, VA, 10Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, 11Cleveland Clinic, Cleveland, OH Purpose/Objective(s): Salvage radiation therapy (SRT) for biochemical failure after radical prostatectomy (RP) is effective at producing a durable prostate-specific antigen (PSA) response. In this collaborative multiinstitutional cohort, we aim to examine the impact of SRT dose in patients (pts) at high risk of residual disease localized to the RP bed, specifically pts with positive surgical margins, and a detectable post-RP/pre-SRT PSA 2.0 ng/mL. Materials/Methods: In this institutional review board-approved retrospective study, 1302 pts underwent RP from 1985 to 2012 with positive surgical margins and negative lymph nodes, followed by SRT without androgen deprivation therapy. All pts had a detectable pre-SRT PSA of
International Journal of Radiation Oncology Biology Physics
301
Results: We identified 541 patients who received salvage RT, of whom 194 received ESRT and had pT3 and/or positive margins. One hundred eightyseven patients received ART for adverse pathologic features. Median follow-up from surgery was 7.0 and 8.9 years in the adjuvant and salvage cohorts, respectively. Median time from surgery to ART was 4.5 months; median time to first detectable PSA after prostatectomy in the salvage cohort was 23.7 months. Of ESRT patients, 3.4% received preoperative ADT, and 9.7% received concurrent ADT. After RT, median time to biochemical recurrence was 4.4 and 5.0 years in the ART and ESRT cohorts, respectively. On MVA, compared to ESRT, ART was associated with improved 10-year FFBF (73.9 vs 59.5%, HR Z 0.36, 95% CI: 0.23e0.58, P < .0001) and 10-year FFADT (91.2 vs 83.2%, HR Z 0.37, 95% CI: 0.18e0.76, P Z .007). There were no significant differences in FFDM (95.8 vs 91.8%, HR Z 0.58, 95% CI: 0.19e1.7, P Z .3), and OS (97.8 vs 95.2%, HR Z 1.24, 95% CI: 0.4e3.89, P Z .7). Matching reduced the median bias caused by differences in baseline characteristics of ESRT (n Z 176) and ART (n Z 169) patients from 24.4% to 3.5% for unmatched and matched groups, respectively. After PS matching, adjuvant RT remained significantly associated with improved FFBF (P < .0001) and FFADT (P Z .01). Conclusion: Postprostatectomy RT confers excellent long-term prostate cancer control, a finding validated by the long follow-up in this series. ART is associated with reduced risk of PSA recurrence and need for subsequent ADT compared to ESRT, although there were no statistically significant differences in freedom from distant metastases and OS. Optimal timing of postoperative RT further awaits the results of ongoing randomized trials. Author Disclosure: D. Buscariollo: None. R.H. Clayman: None. S. Galland: None. A.S. Feldman: None. D.M. Dahl: None. F.J. McGovern: None. A. Olumi: None. A. Eidelman: None. A. Niemierko: None. W.U. Shipley: Stock; Pfizer. A.L. Zietman: Editor; International Journal of Radiation Oncology * Biology * Physics. J.A. Efstathiou: Member; NRG Oncology GU Core Committee, Board of Directors Massachusetts Prostate Cancer Coalition. Co-Chair; NCI Bladder Task Force, NRG Comparative Effectiveness Committee. Chair; ASTRO Genitourinary Cancer Submission Tracks.
PSA After Salvage Radiation Therapy for Postprostatectomy Biochemical Recurrence Predicts Long-term Outcome Including Overall Survival T. Wiegel,1 D. Bartkowiak,1 R. Bottke,1 W. Hinkelbein,2 and A. Siegmann2; 1University Hospital Ulm, Ulm, Germany, 2Charite´ University Hospital Berlin, Berlin, Germany Purpose/Objective(s): For patients with recurrent prostate cancer after radical prostatectomy (RP), salvage radiation therapy (SRT) is a second chance of cure. However, depending on pre-SRT risk factors, 40% to 70% of the patients experience further progression. Furthermore, the post-SRT level of prostate-specific antigen (PSA) is a prognostic marker. We report on the outcome of a cohort of patients who received SRT at 2 German centers. Materials/Methods: Between 1997 and 2011, 464 patients at 2 German centers, Berlin and Ulm, received SRT with 59.4 to 72 Gy (median, 66.6 Gy). All patient had 3-dimensional conformal treatment, including 60 cases with intensity modulated RT/volumetric modulated arc therapy technique. The median pre-SRT PSA was 0.31 ng/mL (interquartile range, 0.15e0.69). Post-SRT progression was defined as either PSA rising >0.2 ng/mL above nadir, or hormone treatment, or clinical recurrence. Data were analyzed with the Kaplan-Meier method (log-rank test) and with multivariate Cox regression. Results: The median follow-up was 5.9 years (maximum 14.4 years). In that time, 178 patients had recurrence and 30 men died. Univariate, a preRP PSA <10 ng/mL, pT<3, Gleason Score (GLS) <8, positive surgical margins R1, a pre-SRT PSA <0.2 ng/mL, and a post-SRT PSA <0.1 ng/ mL related with fewer and later second recurrences. In multivariable analysis, pT, GLS, R, and, most important, the pre-SRT PSA were significant covariates of progression. If the post-SRT PSA was included in the model, then failing the nadir was the most significant predictor of further progression. Achieving a post-SRT PSA <0.1 ng/mL correlated favorably with overall survival, in uni- and multivariable analysis. Conclusion: Early SRT initiated at a PSA <0.2 ng/mL correlates with achieving a post SRT <0.1 ng/mL. Such a response to SRT goes along with better freedom from progression and overall survival. Author Disclosure: T. Wiegel: None. D. Bartkowiak: None. R. Bottke: None. W. Hinkelbein: None. A. Siegmann: None.
302 Long-term Results of Early Salvage Versus Adjuvant Postprostatectomy Radiation: A Large Institutional Experience D. Buscariollo,1 R.H. Clayman,1 S. Galland,2 A.S. Feldman,1 D.M. Dahl,1 F.J. McGovern,1 A. Olumi,1 A. Eidelman,1 A. Niemierko,1 W.U. Shipley,1 A.L. Zietman,3 and J.A. Efstathiou3; 1Massachusetts General Hospital, Boston, MA, 2Bordeaux Hospital University, Bordeaux, Aquitaine, France, 3 Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Randomized trials and consensus statements support consideration of adjuvant radiation therapy (ART) after prostatectomy for adverse pathologic features (pT3, positive margins), although its use remains low. Whether early salvage radiation therapy (ESRT) is as effective as ART remains unknown. Materials/Methods: We performed a retrospective institutional analysis of 728 postprostatectomy patients receiving RT between 1993 and 2012. ESRT was defined as RT for biochemical recurrence with a postoperative prostate-specific antigen (PSA) level of 0.5 ng/mL. Outcomes examined were freedom from biochemical failure (FFBF), freedom from subsequent androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS). ART and ESRT were compared using multivariable analyses (MVA) with propensity score (PS) matching for preoperative PSA, age at the time of RT, pathologic Gleason score, pathologic T-stage, and margin status.
303 Dose Response for Salvage Radiation Therapy After Radical Prostatectomy in Margin-Positive Prostate Cancer S. Agrawal,1 T.M. Pisansky,2 D.A. Hamstra,3 S. Liauw,4 B.F. Koontz,5 J.A. Efstathiou,6 J.M. Michalski,7 F.Y. Feng,3 M.C. Abramowitz,8 A. Pollack,8 M.S. Anscher,9 D. Moghanaki,9 R.B. Den,10 K.L. Stephans,11 M. Kattan,11 A.J. Stephenson,11 and R.D. Tendulkar11; 1Case Western Reserve University School of Medicine, Cleveland, OH, 2Mayo Clinic, Rochester, MN, 3University of Michigan, Ann Arbor, MI, 4University of Chicago, Chicago, IL, 5Duke University Medical Center, Durham, NC, 6 Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7 Washington University School of Medicine, St. Louis, MO, 8University of Miami, Miami, FL, 9Virginia Commonwealth University Medical Center, Richmond, VA, 10Sidney Kimmel Medical College of Thomas Jefferson University, Philadelphia, PA, 11Cleveland Clinic, Cleveland, OH Purpose/Objective(s): Salvage radiation therapy (SRT) for biochemical failure after radical prostatectomy (RP) is effective at producing a durable prostate-specific antigen (PSA) response. In this collaborative multiinstitutional cohort, we aim to examine the impact of SRT dose in patients (pts) at high risk of residual disease localized to the RP bed, specifically pts with positive surgical margins, and a detectable post-RP/pre-SRT PSA 2.0 ng/mL. Materials/Methods: In this institutional review board-approved retrospective study, 1302 pts underwent RP from 1985 to 2012 with positive surgical margins and negative lymph nodes, followed by SRT without androgen deprivation therapy. All pts had a detectable pre-SRT PSA of