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Post–Biochemical Failure Risk Stratification to Predict Survival in Prostate Cancer: A Recursive Partitioning Analysis
E192
International Journal of Radiation Oncology Biology Physics
pelvic EBRT (46 Gy in 23 fractions) using a 4-field conformal technique. Patients in the DEeEBRT arm were then given an additional 32 Gy in 16 fractions to the prostate (total EBRT dose Z 78 Gy in 39 fractions) while those in the experimental arm had a 2-week break from treatment followed by an LDR-PB implant (stranded 125-Iodine sources; prescribed minimum peripheral dose [MPD] Z 115 Gy). The primary endpoint of the trial was PFS using the nadir+2 ng/mL (Phoenix) thresholds for biochemical failure. In this analysis, we are exploring the impact of using a surgical prostatespecific antigen (PSA) threshold of >0.2 ng/mL to define biochemical progression. Initial PSA 20ng/mL, Gleason 8, T stage Z T3a, and 50% positive cores (PPC) were considered to be high-risk features (HRF). Results: Median follow-up was 6.5 years; 96.8% had at least 1 HRF, 35% had 2 HRFs, and 13% had 3 HRFs. Using the nadir+2 ng/mL threshold, men assigned to LDR-PB boost were less than half as likely to have biochemical progression compared to those assigned to DE-EBRT boost. The Cox MV hazard ratio (HR) Z 0.49 (95% CI, 0.20 e 0.80, PZ.004). Using the >0.2 ng/mL threshold to define biochemical progression, the Cox MV HR becomes 0.22 (95% CI, 0.15-0.33, P<.001). The 7-year Kaplan-Meier PFS estimate was 82% for men randomized to LDR-PB boost compared to only 42% for men assigned to DE-EBRT boost (logrank P<.001). This magnitude of benefit exists in both intermediate- and high-risk subgroups. In patients with 2 or fewer high-risk features PFS at 7 years, for LDR-PB arm was 87.2% versus 42.2% for DE-EBRT arm (logrank P<.001). There was no significant difference in the PFS between the 2 arms for patients with 3 or more high-risk features (39.4% in LDR-PB arm vs 16.5% in DE-EBRT arm) (log-rank PZ.138). Conclusion: For men with unfavorable-risk prostate cancer, an LDR-PB boost is much more effective than dose-escalated EBRT in terms of biochemical endpoints. This effect is greatly magnified by replacing the nadir+2 (Phoenix) with surgical threshold of >0.2 ng/mL to define biochemical relapse. This benefit extended to both NCCN intermediate- and high-risk patients but was not apparent in patients with 3 or more HRF, possibly doe to occult metastatic disease prior to treatment. Author Disclosure: S.L. Rodda: None. S. Tyldesley: None. M. Keyes: None. M. McKenzie: None. H.H. Pai: None. G. Duncan: None. J. Hamm: None. W. Morris: None.
score [GS]), radiation/hormonal treatment, and biochemical (initial prostate-specific antigen [PSA], pretreatment PSA doubling time [PSADT], PSA nadir, time to PSA nadir, time to BF [TTBF], and pre-BF PSADT) with OS after BF. Results: UV/MV analysis confirmed age, T stage, GS, radiation modality, hormonal therapy, initial PSA, PSA nadir, TTBF, and pre-BF PSADT as predictors (P<.05) of OS. An RPA identified 6 unique patient groups organized into high-risk (HR, post-BF 5-year survival T: 44% V: 47%) and low-risk (LR, T: 81% V: 69%) categories (see table). OS after BF hazard ratio for HR versus LR categories was 3.87 (95% CI: 2.64-5.68, P<.0001, concordance c statisticZ0.69) and 2.05 (95% CI: 1.22-3.45, PZ.007, cZ0.60) for the T and V sets, respectively. Conclusion: A post-BF risk-stratification system composed of prostate cancer-related factors (TTBF, pre-BF PSADT, and GS) and age has been validated to predict post-BF survival outcome.
2487 PosteBiochemical Failure Risk Stratification to Predict Survival in Prostate Cancer: A Recursive Partitioning Analysis G. Rodrigues,1 T. Wang,1 A. Warner,1 T. Pickles,2 J.M. Crook,3 A.G. Martin,4 E. Vigneault,5 F.L. Cury,6 L. Souhami,7 W.J. Morris,8 C.N. Catton,9 and H. Lukka10; 1London Health Sciences Centre, London, ON, Canada, 2BC Cancer Agency, Vancouver, BC, Canada, 3University of British Columbia, Kelowna, BC, Canada, 4Centre Hospitalier Universitaire de Que´bec, Hoˆtel-Dieu de Que´bec, Quebec, QC, Canada, 5 L’Hotel Dieu de Quebec - CHUQ, Quebec, QC, Canada, 6McGill University Health Centre, Montreal, QC, Canada, 7McGill University Health Center, Montreal, QC, Canada, 8British Columbia Cancer Agency, Vancouver, BC, Canada, 9Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada, 10McMaster University, Hamilton, ON, Canada Purpose/Objective(s): No validated risk stratification system has been developed to identify high-risk (HR) biochemical failures (BF) that lead to premature death. Identification of a HR BF phenotype would assist in decision making regarding salvage treatment, clinical trials, and the definition of a prostate cancer surrogate endpoint. Materials/Methods: This analysis focused on 1246 of 7974 patients from the Prostate Cancer Risk Stratification radiation therapy database all with American Society for Radiation Oncology BF (nadir + 2.0 ng/mL) of which 486 of 1246 (39%) have subsequently died post-BF. These patients were split into training (T, nZ831, 67%) and validation (V, nZ415, 33%) cohorts for univariable (UV), multivariable (MV), and recursive partitioning analyses (RPA) associating patient (age), tumor (stage, Gleason
Poster Viewing Abstracts 2487; Table 1 Training Variable
N
Validating
Median Median (years) 5Y(%) N (years) 5Y(%)
6-Class RPA risk group system Low risk (1): TTBF < 6.5 Y + 209 NR PSADT (Last 2) 5 M + GS 2-7 23 NR Low risk (2): TTBF < 6.5 Y + PSADT (Last 2) < 5 M + Age < 65 Y High Risk (1): TTBF < 6.5 Y + 31 NR PSADT (Last 2) 5 M + GS 8-10 High risk (2):TTBF < 6.5 Y + 48 4.85 PSADT (Last 2) < 5 M + Age 65 Y High risk (3):TTBF 6.5 Y + 32 4.57 PSADT (Nadir + Last) 1 Y High risk (4):TTBF 6.5 Y + 6 0.74 PSADT (Nadir + Last) < 1 Y
81.8
93 NR
72.0
73.9
15 NR
53.3
51.6
16 NR
62.5
45.8
13
3.67
38.5
43.8
17
3.12
41.2
0.0
1 –
–
Author Disclosure: G. Rodrigues: Independent Contractor; London Health Sciences Centre. Research Grant; Janssen Inc. T. Wang: None. A. Warner: None. T. Pickles: Research Grant; Oncura Corporation. J.M. Crook: None. A. Martin: None. E. Vigneault: None. F.L. Cury: None. L. Souhami: None. W. Morris: Research Grant; Oncura Corporation. C.N. Catton: None. H. Lukka: None.
2488 Prospective, Randomized, Patient-Blinded, Multicenter Trial of Perirectal Spacer in Men Undergoing Prostate IG-IMRT: Dosimetry and Toxicity Evaluation R.J. Ellis, III,1 N.F. Mariados,2 J.E. Sylvester,3 D.K. Shah,4 L. Karsh,5 R.S. Hudes,6 D.C. Beyer,7 S.M. Kurtzman,8 J.A. Bogart,9 R.A. Hsi,10 M. Kos,11 M.D. Logsdon,12 S.H. Zimberg,13 K. Forsythe,14 H. Zhang,15 E.M. Soffen,16 P.M. Francke,3 C.A. Mantz,3 P.J. Rossi,17 and T.L. DeWeese18,19; 1University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, 2Associated Medical Professionals of NY PLLC, Syracuse, NY, 321st Century Oncology, Fort Myers, FL, 4Cancer Care of Western New York, Cheektowaga, NY, 5The Urology Center of Colorado, Denver, CO, 6Chesapeake Urology Research Associates, Owings Mills, MD, 7Foundation for Cancer Research and Education, Phoenix, AZ, 8Urological Surgeons of Northern California, Inc., Campbell, CA, 9SUNY Upstate Medical University, Syracuse, NY, 10 Peninsula Cancer Center, Poulsbo, WA, 11Urology Nevada, Reno, NV, 12 Sutter Institute for Medical Research, Sacramento, CA, 13Advanced Radiation Centers of New York, Hauppauge, NY, 14Oregon Urology Institute, Springfield, OR, 15Wilmot Cancer Institute, University of Rochester, Rochester, NY, 16Princeton Radiation Oncology, Jamesburg, NJ, 17 Emory University, Atlanta, GA, 18Johns Hopkins University Medical Center, Baltimore, MD, 19Johns Hopkins University, Baltimore, MD
International Journal of Radiation Oncology Biology Physics
pelvic EBRT (46 Gy in 23 fractions) using a 4-field conformal technique. Patients in the DEeEBRT arm were then given an additional 32 Gy in 16 fractions to the prostate (total EBRT dose Z 78 Gy in 39 fractions) while those in the experimental arm had a 2-week break from treatment followed by an LDR-PB implant (stranded 125-Iodine sources; prescribed minimum peripheral dose [MPD] Z 115 Gy). The primary endpoint of the trial was PFS using the nadir+2 ng/mL (Phoenix) thresholds for biochemical failure. In this analysis, we are exploring the impact of using a surgical prostatespecific antigen (PSA) threshold of >0.2 ng/mL to define biochemical progression. Initial PSA 20ng/mL, Gleason 8, T stage Z T3a, and 50% positive cores (PPC) were considered to be high-risk features (HRF). Results: Median follow-up was 6.5 years; 96.8% had at least 1 HRF, 35% had 2 HRFs, and 13% had 3 HRFs. Using the nadir+2 ng/mL threshold, men assigned to LDR-PB boost were less than half as likely to have biochemical progression compared to those assigned to DE-EBRT boost. The Cox MV hazard ratio (HR) Z 0.49 (95% CI, 0.20 e 0.80, PZ.004). Using the >0.2 ng/mL threshold to define biochemical progression, the Cox MV HR becomes 0.22 (95% CI, 0.15-0.33, P<.001). The 7-year Kaplan-Meier PFS estimate was 82% for men randomized to LDR-PB boost compared to only 42% for men assigned to DE-EBRT boost (logrank P<.001). This magnitude of benefit exists in both intermediate- and high-risk subgroups. In patients with 2 or fewer high-risk features PFS at 7 years, for LDR-PB arm was 87.2% versus 42.2% for DE-EBRT arm (logrank P<.001). There was no significant difference in the PFS between the 2 arms for patients with 3 or more high-risk features (39.4% in LDR-PB arm vs 16.5% in DE-EBRT arm) (log-rank PZ.138). Conclusion: For men with unfavorable-risk prostate cancer, an LDR-PB boost is much more effective than dose-escalated EBRT in terms of biochemical endpoints. This effect is greatly magnified by replacing the nadir+2 (Phoenix) with surgical threshold of >0.2 ng/mL to define biochemical relapse. This benefit extended to both NCCN intermediate- and high-risk patients but was not apparent in patients with 3 or more HRF, possibly doe to occult metastatic disease prior to treatment. Author Disclosure: S.L. Rodda: None. S. Tyldesley: None. M. Keyes: None. M. McKenzie: None. H.H. Pai: None. G. Duncan: None. J. Hamm: None. W. Morris: None.
score [GS]), radiation/hormonal treatment, and biochemical (initial prostate-specific antigen [PSA], pretreatment PSA doubling time [PSADT], PSA nadir, time to PSA nadir, time to BF [TTBF], and pre-BF PSADT) with OS after BF. Results: UV/MV analysis confirmed age, T stage, GS, radiation modality, hormonal therapy, initial PSA, PSA nadir, TTBF, and pre-BF PSADT as predictors (P<.05) of OS. An RPA identified 6 unique patient groups organized into high-risk (HR, post-BF 5-year survival T: 44% V: 47%) and low-risk (LR, T: 81% V: 69%) categories (see table). OS after BF hazard ratio for HR versus LR categories was 3.87 (95% CI: 2.64-5.68, P<.0001, concordance c statisticZ0.69) and 2.05 (95% CI: 1.22-3.45, PZ.007, cZ0.60) for the T and V sets, respectively. Conclusion: A post-BF risk-stratification system composed of prostate cancer-related factors (TTBF, pre-BF PSADT, and GS) and age has been validated to predict post-BF survival outcome.
2487 PosteBiochemical Failure Risk Stratification to Predict Survival in Prostate Cancer: A Recursive Partitioning Analysis G. Rodrigues,1 T. Wang,1 A. Warner,1 T. Pickles,2 J.M. Crook,3 A.G. Martin,4 E. Vigneault,5 F.L. Cury,6 L. Souhami,7 W.J. Morris,8 C.N. Catton,9 and H. Lukka10; 1London Health Sciences Centre, London, ON, Canada, 2BC Cancer Agency, Vancouver, BC, Canada, 3University of British Columbia, Kelowna, BC, Canada, 4Centre Hospitalier Universitaire de Que´bec, Hoˆtel-Dieu de Que´bec, Quebec, QC, Canada, 5 L’Hotel Dieu de Quebec - CHUQ, Quebec, QC, Canada, 6McGill University Health Centre, Montreal, QC, Canada, 7McGill University Health Center, Montreal, QC, Canada, 8British Columbia Cancer Agency, Vancouver, BC, Canada, 9Princess Margaret Cancer Centre / University of Toronto, Toronto, ON, Canada, 10McMaster University, Hamilton, ON, Canada Purpose/Objective(s): No validated risk stratification system has been developed to identify high-risk (HR) biochemical failures (BF) that lead to premature death. Identification of a HR BF phenotype would assist in decision making regarding salvage treatment, clinical trials, and the definition of a prostate cancer surrogate endpoint. Materials/Methods: This analysis focused on 1246 of 7974 patients from the Prostate Cancer Risk Stratification radiation therapy database all with American Society for Radiation Oncology BF (nadir + 2.0 ng/mL) of which 486 of 1246 (39%) have subsequently died post-BF. These patients were split into training (T, nZ831, 67%) and validation (V, nZ415, 33%) cohorts for univariable (UV), multivariable (MV), and recursive partitioning analyses (RPA) associating patient (age), tumor (stage, Gleason
Poster Viewing Abstracts 2487; Table 1 Training Variable
N
Validating
Median Median (years) 5Y(%) N (years) 5Y(%)
6-Class RPA risk group system Low risk (1): TTBF < 6.5 Y + 209 NR PSADT (Last 2) 5 M + GS 2-7 23 NR Low risk (2): TTBF < 6.5 Y + PSADT (Last 2) < 5 M + Age < 65 Y High Risk (1): TTBF < 6.5 Y + 31 NR PSADT (Last 2) 5 M + GS 8-10 High risk (2):TTBF < 6.5 Y + 48 4.85 PSADT (Last 2) < 5 M + Age 65 Y High risk (3):TTBF 6.5 Y + 32 4.57 PSADT (Nadir + Last) 1 Y High risk (4):TTBF 6.5 Y + 6 0.74 PSADT (Nadir + Last) < 1 Y
81.8
93 NR
72.0
73.9
15 NR
53.3
51.6
16 NR
62.5
45.8
13
3.67
38.5
43.8
17
3.12
41.2
0.0
1 –
–
Author Disclosure: G. Rodrigues: Independent Contractor; London Health Sciences Centre. Research Grant; Janssen Inc. T. Wang: None. A. Warner: None. T. Pickles: Research Grant; Oncura Corporation. J.M. Crook: None. A. Martin: None. E. Vigneault: None. F.L. Cury: None. L. Souhami: None. W. Morris: Research Grant; Oncura Corporation. C.N. Catton: None. H. Lukka: None.
2488 Prospective, Randomized, Patient-Blinded, Multicenter Trial of Perirectal Spacer in Men Undergoing Prostate IG-IMRT: Dosimetry and Toxicity Evaluation R.J. Ellis, III,1 N.F. Mariados,2 J.E. Sylvester,3 D.K. Shah,4 L. Karsh,5 R.S. Hudes,6 D.C. Beyer,7 S.M. Kurtzman,8 J.A. Bogart,9 R.A. Hsi,10 M. Kos,11 M.D. Logsdon,12 S.H. Zimberg,13 K. Forsythe,14 H. Zhang,15 E.M. Soffen,16 P.M. Francke,3 C.A. Mantz,3 P.J. Rossi,17 and T.L. DeWeese18,19; 1University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Cleveland, OH, 2Associated Medical Professionals of NY PLLC, Syracuse, NY, 321st Century Oncology, Fort Myers, FL, 4Cancer Care of Western New York, Cheektowaga, NY, 5The Urology Center of Colorado, Denver, CO, 6Chesapeake Urology Research Associates, Owings Mills, MD, 7Foundation for Cancer Research and Education, Phoenix, AZ, 8Urological Surgeons of Northern California, Inc., Campbell, CA, 9SUNY Upstate Medical University, Syracuse, NY, 10 Peninsula Cancer Center, Poulsbo, WA, 11Urology Nevada, Reno, NV, 12 Sutter Institute for Medical Research, Sacramento, CA, 13Advanced Radiation Centers of New York, Hauppauge, NY, 14Oregon Urology Institute, Springfield, OR, 15Wilmot Cancer Institute, University of Rochester, Rochester, NY, 16Princeton Radiation Oncology, Jamesburg, NJ, 17 Emory University, Atlanta, GA, 18Johns Hopkins University Medical Center, Baltimore, MD, 19Johns Hopkins University, Baltimore, MD