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Risk Factors for Disease Progression After Postprostatectomy Salvage Radiation: Long-Term Results of a Large Institutional Experience
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Volume 96 Number 2S Supplement 2016
2605 Risk Factors for Disease Progression After Postprostatectomy Salvage Radiation: Long-Term Results of a Large Institutional Experience D. Rodin,1 L.W. Andersen,2 D. Buscariollo,3 M.R. Drumm,4 R.H. Clayman,4 S. Galland,5 A. Eidelman,4 A.S. Feldman,6 R.J. Lee,4 D.M. Dahl,6 F.J. McGovern,6 A. Olumi,6 A. Niemierko,7 W.U. Shipley,4 A.L. Zietman,4 and J.A. Efstathiou4; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 2Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark, 3DanaFarber Cancer Institute, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5 Bordeaux Hospital University, Bordeaux, France, 6Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Salvage radiation therapy (SRT) has been successfully used to treat recurrent prostate cancer following radical prostatectomy (RP). The objective of this study was to identify risk factors for disease progression post-SRT. The hypothesis is that absolute PSA prior to SRT can be effectively used to predict time to disease progression in the contemporary era of PSA testing. Materials/Methods: Retrospective review of 719 consecutive patients who had RP and received post-operative radiation (adjuvant/SRT) for recurrent prostate cancer from 1992-2013. The following exclusion criteria were applied: metastatic disease, hormone therapy prior to or concurrent with SRT, adjuvant radiation, and SRT prior to 2000. Disease progression was defined as a repeat PSA 0.2 ng/ml above the post-SRT nadir, a continued rise in PSA despite SRT, initiation of systemic therapy, local recurrence, nodal failure, or distant metastases. Univariable and multivariable Cox regression analysis with backwards selection was performed with the following variables: demographics (age, race), pathological features (Gleason score, positive margins, T-stage), surgery type, radiation details (volumes, dose, technique), time (time from RP to SRT, year of SRT), and PSA (pre-operatively, post-operatively, and pre-SRT). Secondarily, PSA doubling time (DT) and velocity as continuous and categorical variables were evaluated for inclusion in the model and compared using the Akaike information criterion. Results: 306 patients received SRT after 2000, of which 165 had disease progression, with a median time to recurrence of 6.0 years (95% CI 3.7-8.4 years). On multivariable analysis, Gleason score, T-stage, positive margins, and pre-SRT PSA were associated with progression. When the pre-SRT PSA was 0.5, no statistically significant differences were found in time to disease progression with incremental PSA increases of 0.1. An increased rate of disease progression was seen only when the PSA was greater than 0.5 (HR 1.92, 95% CI 1.05-3.50) or greater than 1.0 (3.74, 95% CI 1.817.74). In a secondary model, PSA-DT as a categorical variable (>6 months) provided the best model fit. When PSA-DT was included in the multivariable model, pre-SRT PSA was only a significant predictor of progression at values >1.0 (HR 3.87, 95% CI 1.63-9.22). Conclusion: The lowest rate of disease progression was found amongst patients treated at a PSA 0.5. In patients with a short PSA-DT, absolute PSA values <1.0 may not be the most useful predictors of disease progression after SRT. Although patients on hormone therapy were excluded, these findings may help to select patients at high risk of progression following SRT who may derive the greatest benefit from additional systemic treatment. Author Disclosure: D. Rodin: None. L.W. Andersen: None. D. Buscariollo: None. M.R. Drumm: None. R.H. Clayman: None. S. Galland: None. A. Eidelman: None. A.S. Feldman: Independent Contractor; Olympus America, Inc. R.J. Lee: None. D.M. Dahl: None. F.J. McGovern: None. A. Olumi: None. A. Niemierko: None. W.U. Shipley: None. A.L. Zietman: None. J.A. Efstathiou: Safety Review Committee; Bayer Healthcare. Advisor; GenomeDx. Chair of GU Track; ASTRO GU Track. Co-Chair of the Task force; NCI Bladder Task Force. Board of
Directors of Coalition; Massachusetts Prostate Cancer Coalition. Co-Chair of NRG Comparative Effectiveness Committee; NRG Comparative Effectiveness Committee. Member of committee; NRG Oncology GU Core Committee.
2606 Pelvic Volumetric Modulated Arc Therapy (VMAT) for Prostate for Locally Advanced Prostate Cancer F. Ferrer,1,2 K. Ballon,3 A. Boladeras,1 R. De Blas,4 D. Najjari,1 M. Ventura,1 P. Bavestrello,1 F. Rojas,1 S. Bejar,1 E. Zardoya,4 E. Martinez,1 S. Comas,5 C. Gutierrez,1,2 J. Pera,1 C. Picon,4 and F. Guedea1,2; 1Radiation Oncology Department. Catalan Institute of Oncology, L’Hospitalet-Barcelona, Spain, 2University of Barcelona, L’Hospitalet-Barcelona, Spain, 3Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru, 4Physics Department. Catalan Institute of Oncology, L’Hospitalet-Barcelona, Spain, 5Radiation Oncology Department. Catalan Institute of Oncology, Badalona-Barcelona, Spain Purpose/Objective(s): To report toxicity of pelvic VMAT with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with high-risk or very high risk prostate cancer. Materials/Methods: Eighty-three consecutive patients (pts), diagnosed with high risk or locally advanced prostate cancer, were treated between June 2011 and May 2015 with SIB-VMAT. All of them also received androgen suppression. On the planning-CT CTV1 (prostate), CTV2 (CTV1 plus seminal vesicles) and CTV3 (CTV2 plus pelvic nodes) were delineated. CTVs were expanded to generate the planning target volumes (PTV). The VMAT plans were designed to deliver 67,5 Gy in 27 fractions (2.5 Gy/fr) to the prostate, 59,4 Gy (2,2Gy/fr) while delivering simultaneously 48.6 Gy in 27 fractions(1.8 Gy/fr) to the pelvic lymph nodes. In pts with N1, dose was increased to 59.4 Gy at 2.2 Gy given simultaneously, and HDR brachytherapy 9 Gy/1 fr was done in unfavorable dosimetry for integrated boost to the prostate. Toxicity was scored by CTCAEv4.0. Univariate and multivariate analysis were performed looking for correlations among patient characteristics, dose values and toxicity. Results: Median age of patients (pts) was 70 years old. Gleason score was >Z8 in 70% of pts. The median follow-up was 30 months (from 6 to 50 months). All received the prescribed external radiation dose in 27 fractions. Sixty-two patients received 67.5 Gy to the CTV1 plus margin at 2.5 Gy per fraction. Brachytherapy boost was performed in 21 pts delivering 9 Gy in one fraction over 59.4 Gy at 2.2 to the CTV2 plus margin. Four pts died (one for a second tumor and the other three for prostate cancer progression). The most common acute event was urinary frequency/urgency (90%). Acute urinary toxicity was scored as 1 in 70% of pts. Rectal acute toxicity grade 2 (G2) with mucosal discharge was present in 40% of pts. No late toxicity exceeding G2 was rectal toxicity G2 or less was 25%. Urinary toxicity G2 or less was 40%. G2 acute or late bowel toxicity was seen in 8% and 4% respectively. G2 acute or late bowel toxicity was not associated with bowel volume receiving V30, V40, V50, or V60Gy. Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic VMAT with SIB or sequential HDR brachytherapy to the prostate were well tolerated in this series, with acceptable rates of acute and subacute toxicity. SIB-VMAT combines pelvic radiation therapy and hypofractionation to the primary site and offers an accelerated approach to treating high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression. Author Disclosure: F. Ferrer: None. K. Ballon: None. A. Boladeras: None. R. De Blas: None. D. Najjari: None. M. Ventura: None. P. Bavestrello: None. F. Rojas: None. S. Bejar: None. E. Zardoya: None. E. Martinez: None. S. Comas: None. C. Gutierrez: None. J. Pera: None. C. Picon: None. F. Guedea: None.
Volume 96 Number 2S Supplement 2016
2605 Risk Factors for Disease Progression After Postprostatectomy Salvage Radiation: Long-Term Results of a Large Institutional Experience D. Rodin,1 L.W. Andersen,2 D. Buscariollo,3 M.R. Drumm,4 R.H. Clayman,4 S. Galland,5 A. Eidelman,4 A.S. Feldman,6 R.J. Lee,4 D.M. Dahl,6 F.J. McGovern,6 A. Olumi,6 A. Niemierko,7 W.U. Shipley,4 A.L. Zietman,4 and J.A. Efstathiou4; 1Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada, 2Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark, 3DanaFarber Cancer Institute, Boston, MA, 4Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 5 Bordeaux Hospital University, Bordeaux, France, 6Department of Urology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, 7Department of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA Purpose/Objective(s): Salvage radiation therapy (SRT) has been successfully used to treat recurrent prostate cancer following radical prostatectomy (RP). The objective of this study was to identify risk factors for disease progression post-SRT. The hypothesis is that absolute PSA prior to SRT can be effectively used to predict time to disease progression in the contemporary era of PSA testing. Materials/Methods: Retrospective review of 719 consecutive patients who had RP and received post-operative radiation (adjuvant/SRT) for recurrent prostate cancer from 1992-2013. The following exclusion criteria were applied: metastatic disease, hormone therapy prior to or concurrent with SRT, adjuvant radiation, and SRT prior to 2000. Disease progression was defined as a repeat PSA 0.2 ng/ml above the post-SRT nadir, a continued rise in PSA despite SRT, initiation of systemic therapy, local recurrence, nodal failure, or distant metastases. Univariable and multivariable Cox regression analysis with backwards selection was performed with the following variables: demographics (age, race), pathological features (Gleason score, positive margins, T-stage), surgery type, radiation details (volumes, dose, technique), time (time from RP to SRT, year of SRT), and PSA (pre-operatively, post-operatively, and pre-SRT). Secondarily, PSA doubling time (DT) and velocity as continuous and categorical variables were evaluated for inclusion in the model and compared using the Akaike information criterion. Results: 306 patients received SRT after 2000, of which 165 had disease progression, with a median time to recurrence of 6.0 years (95% CI 3.7-8.4 years). On multivariable analysis, Gleason score, T-stage, positive margins, and pre-SRT PSA were associated with progression. When the pre-SRT PSA was 0.5, no statistically significant differences were found in time to disease progression with incremental PSA increases of 0.1. An increased rate of disease progression was seen only when the PSA was greater than 0.5 (HR 1.92, 95% CI 1.05-3.50) or greater than 1.0 (3.74, 95% CI 1.817.74). In a secondary model, PSA-DT as a categorical variable (>6 months) provided the best model fit. When PSA-DT was included in the multivariable model, pre-SRT PSA was only a significant predictor of progression at values >1.0 (HR 3.87, 95% CI 1.63-9.22). Conclusion: The lowest rate of disease progression was found amongst patients treated at a PSA 0.5. In patients with a short PSA-DT, absolute PSA values <1.0 may not be the most useful predictors of disease progression after SRT. Although patients on hormone therapy were excluded, these findings may help to select patients at high risk of progression following SRT who may derive the greatest benefit from additional systemic treatment. Author Disclosure: D. Rodin: None. L.W. Andersen: None. D. Buscariollo: None. M.R. Drumm: None. R.H. Clayman: None. S. Galland: None. A. Eidelman: None. A.S. Feldman: Independent Contractor; Olympus America, Inc. R.J. Lee: None. D.M. Dahl: None. F.J. McGovern: None. A. Olumi: None. A. Niemierko: None. W.U. Shipley: None. A.L. Zietman: None. J.A. Efstathiou: Safety Review Committee; Bayer Healthcare. Advisor; GenomeDx. Chair of GU Track; ASTRO GU Track. Co-Chair of the Task force; NCI Bladder Task Force. Board of
Directors of Coalition; Massachusetts Prostate Cancer Coalition. Co-Chair of NRG Comparative Effectiveness Committee; NRG Comparative Effectiveness Committee. Member of committee; NRG Oncology GU Core Committee.
2606 Pelvic Volumetric Modulated Arc Therapy (VMAT) for Prostate for Locally Advanced Prostate Cancer F. Ferrer,1,2 K. Ballon,3 A. Boladeras,1 R. De Blas,4 D. Najjari,1 M. Ventura,1 P. Bavestrello,1 F. Rojas,1 S. Bejar,1 E. Zardoya,4 E. Martinez,1 S. Comas,5 C. Gutierrez,1,2 J. Pera,1 C. Picon,4 and F. Guedea1,2; 1Radiation Oncology Department. Catalan Institute of Oncology, L’Hospitalet-Barcelona, Spain, 2University of Barcelona, L’Hospitalet-Barcelona, Spain, 3Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru, 4Physics Department. Catalan Institute of Oncology, L’Hospitalet-Barcelona, Spain, 5Radiation Oncology Department. Catalan Institute of Oncology, Badalona-Barcelona, Spain Purpose/Objective(s): To report toxicity of pelvic VMAT with hypofractionated simultaneous integrated boost (SIB) to the prostate for patients with high-risk or very high risk prostate cancer. Materials/Methods: Eighty-three consecutive patients (pts), diagnosed with high risk or locally advanced prostate cancer, were treated between June 2011 and May 2015 with SIB-VMAT. All of them also received androgen suppression. On the planning-CT CTV1 (prostate), CTV2 (CTV1 plus seminal vesicles) and CTV3 (CTV2 plus pelvic nodes) were delineated. CTVs were expanded to generate the planning target volumes (PTV). The VMAT plans were designed to deliver 67,5 Gy in 27 fractions (2.5 Gy/fr) to the prostate, 59,4 Gy (2,2Gy/fr) while delivering simultaneously 48.6 Gy in 27 fractions(1.8 Gy/fr) to the pelvic lymph nodes. In pts with N1, dose was increased to 59.4 Gy at 2.2 Gy given simultaneously, and HDR brachytherapy 9 Gy/1 fr was done in unfavorable dosimetry for integrated boost to the prostate. Toxicity was scored by CTCAEv4.0. Univariate and multivariate analysis were performed looking for correlations among patient characteristics, dose values and toxicity. Results: Median age of patients (pts) was 70 years old. Gleason score was >Z8 in 70% of pts. The median follow-up was 30 months (from 6 to 50 months). All received the prescribed external radiation dose in 27 fractions. Sixty-two patients received 67.5 Gy to the CTV1 plus margin at 2.5 Gy per fraction. Brachytherapy boost was performed in 21 pts delivering 9 Gy in one fraction over 59.4 Gy at 2.2 to the CTV2 plus margin. Four pts died (one for a second tumor and the other three for prostate cancer progression). The most common acute event was urinary frequency/urgency (90%). Acute urinary toxicity was scored as 1 in 70% of pts. Rectal acute toxicity grade 2 (G2) with mucosal discharge was present in 40% of pts. No late toxicity exceeding G2 was rectal toxicity G2 or less was 25%. Urinary toxicity G2 or less was 40%. G2 acute or late bowel toxicity was seen in 8% and 4% respectively. G2 acute or late bowel toxicity was not associated with bowel volume receiving V30, V40, V50, or V60Gy. Acute or late bladder and rectal toxicity did not correlate with any of the dosimetric parameters examined. Conclusion: Pelvic VMAT with SIB or sequential HDR brachytherapy to the prostate were well tolerated in this series, with acceptable rates of acute and subacute toxicity. SIB-VMAT combines pelvic radiation therapy and hypofractionation to the primary site and offers an accelerated approach to treating high-risk disease. Additional follow-up is necessary to fully define the long-term toxicity after hypofractionated, whole pelvic treatment combined with androgen suppression. Author Disclosure: F. Ferrer: None. K. Ballon: None. A. Boladeras: None. R. De Blas: None. D. Najjari: None. M. Ventura: None. P. Bavestrello: None. F. Rojas: None. S. Bejar: None. E. Zardoya: None. E. Martinez: None. S. Comas: None. C. Gutierrez: None. J. Pera: None. C. Picon: None. F. Guedea: None.