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Serum Testosterone Changes in Patients Treated With Radiation Therapy Alone for Prostate Cancer on RTOG 9408
Volume 87 Number 2S Supplement 2013
306 Cell Cycle Progression (CCP) Score Significantly Predicts PSA Failure After EBRT J.K. Salama,1 S. Freedland,2 L. Gerber,2 J. Reid,3 W. Welbourn,3 A. Gutin,3 Z. Sangale,3 M. Brawer,3 and S. Stone3; 1Duke University, Durham, NC, 2Durham VA Medical Center and Duke University School of Medicine, Durham, NC, 3Myriad Genetics, Inc., Salt Lake City, UT Purpose/Objective(s): Accurate risk stratification is crucial to aid appropriate decision making in localized prostate cancer. To address this need, we have developed the Cell Cycle Progression (CCP) score, based on the collective gene expression of 31 cell cycle genes. To date, this score has been shown to not only predict BCR after prostatectomy, but also prostate cancer specific mortality in men undergoing observation in the United Kingdom. However, the value of this score based upon needle biopsies in men undergoing primary EBRT is untested. Materials/Methods: The CCP score was evaluated retrospectively in 152 patients treated with EBRT. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. CCP score was derived from diagnostic biopsy. Outcome was time from EBRT to biochemical recurrence (BCR) using Phoenix definition, and median follow-up for patients without BCR was 5 years. Of the 152 initially selected patients, 6 were excluded due to delayed treatment (> 2 years from diagnosis) and 5 generated poor quality CCP scores, leaving 141 patients for analysis. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests. Results: Patient data was censored at 5-years of follow-up, 16 patients (11%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariate analysis, CCP score was the most significant prognostic variable (p-value Z 0.002). The hazard ratio (HR) for BCR was 2.71 (95% CI, 1.44, 5.09) for a one-unit increase in CCP score. In a predefined multivariate analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP remained largely unchanged (HR per CCP unit 2.53 (95% CI, 1.14, 5.61; p-value Z 0.019) demonstrating that CCP provides prognostic information that is largely not provided by clinical parameters. There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: We have evaluated the prognostic utility of CCP score for predicting BCR after EBRT. The CCP score was strongly associated with BCR and provided prognostic information beyond what is available from clinical parameters. If these results are validated in a larger cohort, then CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer. Author Disclosure: J.K. Salama: None. S. Freedland: None. L. Gerber: None. J. Reid: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. W. Welbourn: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. A. Gutin: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. Z. Sangale: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. M. Brawer: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. S. Stone: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc.
307 Validation of a Genomic Classifier That Predicts Metastatic Disease Progression in Men With Biochemical Recurrence Post-Radical Prostatectomy F.Y. Feng,1 M. Ghadessi,2 E. Davicioni,2 A. Crisan,2 N. Erho,2 A.P. Mitra,3 T.J. Triche,2 R.B. Jenkins,4 A.E. Ross,4 and E.M. Schaeffer4; 1University of Michigan, Ann Arbor, MI, 2GenomeDx Biosciences, Vancouver, BC, Canada, 3University of Southern California, Los Angeles, CA, 4Johns Hopkins Medical Institute, Baltimore, MD Purpose/Objective(s): Almost 50,000 men per year will present with biochemical recurrence (BCR) following local treatment for prostate cancer. These men with rising PSAs as the lone indicator of recurrence present a management dilemma due to their varied outcomes, as only
Oral Scientific Sessions S125 a proportion subsequently develop metastatic disease. Thus, there is a clear need to improve patient risk stratification in this context. Here, we evaluate a genomic classifier (GC) in men with BCR following radical prostatectomy (RP) for its ability to predict metastasis. Materials/Methods: The 22-marker GC was validated in a prospectively designed case-cohort study of 1,010 clinically high-risk RP patients. Two hundred nineteen patients, including 85 who developed BCR at least 6 months post-RP were subjected to microarray analysis and GC scores were generated. Survival ROC curves, weighted Cox proportional hazards, and decision curves were used to compare the performance of the GC to Gleason score (GS), PSA doubling time (PSAdT) and time to BCR (ttBCR). Results: Of the 85 patients with BCR after RP, 46% had a low GC score and 54% had a high score (using a pre-specified cut point of 0.4 identified during previous development of the GC panel.) GC scores significantly stratified men with BCR into those who would or would not develop subsequent metastasis. Forty percent of patients with a high GC score (versus 8% with a low GC score) developed metastasis at 3 years following BCR depending on GC score category, p < 0.001). The AUC (for prediction of subsequent metastases) was 0.82 (95% CI, 0.76-0.86) for GC, compared to 0.64 (0.58-0.70) for GS, 0.69 (0.61-0.77) for PSAdT and 0.52 (0.46-0.59) for ttBCR. In decision curve analysis, the GC had the highest overall net benefit, and in multivariable modeling with clinicopathologic variables, only GC (p Z 0.006) and GS (p Z 0.046) scores were significant predictors of metastasis. Conclusions: When compared to clinicopathologic variables, the GC better predicted metastatic progression among men with BCR following RP. While confirmatory studies in additional patient populations are required, these results suggest that use of the GC can allow for better selection of men requiring intensification of therapy, such as the addition of androgen deprivation therapy to salvage radiation, at the time of BCR. These results also support the rationale for further efforts to identify genomic-based prognostic or predictive factors in patients treated with radiation therapy for prostate cancer. Author Disclosure: F.Y. Feng: None. C. Buerki: A. Employee; GenomeDx Biosciences. M. Ghadessi: A. Employee; GenomeDx Biosciences. E. Davicioni: A. Employee; GenomeDx Biosciences. K. Stock; GenomeDx Biosciences. Q. Leadership; GenomeDx Biosciences. A. Crisan: A. Employee; GenomeDx Biosciences. N. Erho: A. Employee; GenomeDx Biosciences. A.P. Mitra: None. T.J. Triche: A. Employee; GenomeDx Biosciences. K. Stock; GenomeDx Biosciences. Q. Leadership; GenomeDx Biosciences. A.E. Ross: None. E.M. Schaeffer: None.
308 Serum Testosterone Changes in Patients Treated With Radiation Therapy Alone for Prostate Cancer on RTOG 9408 R. Nichols,1 A. George,2 J. Bahary,3 K.L. Zeitzer,4 L. Souhami,5 M.H. Leibenhaut,6 M. Rotman,7 E.M. Gore,8 A.G. Balogh,9 and C.U. Jones6; 1University of Florida Proton Therapy Institute, Jacksonville, FL, 2RTOG Statistical Center, Philadelphia, PA, 3Centre Hospitalier de l‘Universite´ de Montre´al-Notre Dame, Montreal, QC, Canada, 4Albert Einstein Cancer Center, Philadelphia, PA, 5McGill University, Montreal, QC, Canada, 6Radiological Associates of Sacramento, Sacramento, CA, 7Brooklyn MB-CCOP/SUNY Downstate, New York, NY, 8Medical College of Wisconsin, Milwaukee, WI, 9Tom Baker Cancer Centre, Calgary, AB, Canada Purpose/Objective(s): In light of studies suggesting that radiation therapy (XRT) may influence serum testosterone (ST) levels for patients treated for localized prostate cancer, we reviewed data on testosterone changes for patients treated with XRT alone on RTOG 9408. Materials/Methods: Patients enrolled on RTOG 9408 (T1b-T2b, PSA < 20 ng/mL) were randomized between XRT alone and XRT plus 4 months of total androgen ablation. XRT consisted of either whole pelvic radiation therapy to 46.8 Gy plus a 19.8 Gy prostate boost for a total dose of 66.6 Gy (WPRT) or treatment to the prostate alone for a total dose of 68.4 Gy (PORT). Most patients received WPRT. Only patients with the
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lowest risk features (PSA < 10 ng/mL and Gleason score 5 or a negative lymph node dissection) were assigned to receive PORT. XRT was delivered at 1.8 Gy per fraction. For this analysis, ST levels were investigated at the following collection periods: at study enrollment; completion of XRT; and at first follow-up 3 months after completion of XRT. The Wilcoxon signed rank test was used to compare change in pre and post treatment ST levels in patients who were randomized to the XRT alone arm. Results: Two thousand twenty-eight patients were enrolled on RTOG 9408. Nine hundred ninety-two were randomized to receive XRT alone. Nine hundred four (91%) of these patients had baseline ST values available and completed XRT. Of these 904, immediate and 3 month post XRT testosterone levels were available for 768 and 553 respectively. Excluding 10 patients who received hormonal therapy off protocol, 766 and 543 respectively, were analyzed. Pre-treatment median testosterone level for all patients was 370 ng/dL (P5-P95 Z 167 to 926) which did not differ significantly between the WPRT and PORT groups. For the entire group, at completion of XRT (median Z -26 ng/dL, P5-P95 Z -310 to 360; p < 0.01) and at the 3 month follow-up (median Z -33 ng/dL, P5-P95 Z -300 to 238; p < 0.01), median change in ST showed a statistically significant trend, indicating a decrease in ST level from baseline. For evaluable patients treated with WPRT (679 at end of XRT and 476 at 3-month follow-up), median change in ST is -29 ng/dL (P5-P95 Z -365 to 452; p < 0.01) and -33 ng/dL (P5-P95 Z -313 to 245; p < 0.01), respectively. Patients treated with PORT (87 at end of XRT and 67 at 3-month followup), median change in ST is -12 ng/dL (P5-P95 Z -202 to 101; p Z 0.01) and -37 ng/dL (P5-P95 Z -240 to 110; p < 0.01), respectively. Conclusions: XRT for prostate cancer, as delivered on RTOG 9408, was associated with statistically significant change in ST, indicating a decline. This may be secondary to scatter radiation to the Leydig cells. We have no evidence that these changes in ST have any direct impact on PSA control rates or on post treatment quality of life. Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). Author Disclosure: R. Nichols: None. A. George: None. J. Bahary: None. K.L. Zeitzer: None. L. Souhami: None. M.H. Leibenhaut: None. M. Rotman: None. E.M. Gore: None. A.G. Balogh: None. C.U. Jones: None.
82% (p Z .04), respectively. On multivariate analysis, SV implantation lost its significant effect with only Androgen Deprivation use (p Z .01) and total BED (p < .0001) predictive of biochemical control as well as Gleason Score (p Z .009), initial PSA (p Z .006), and NCCN risk grouping (p Z .006). The 5 year freedom from rectal bleeding was equivalent between those with implanted SVs and those without (94 and 93.5%, respectively). Of the 916 men with full potency at baseline, 255 (27.8%) were no longer potent at last follow-up. SV implantation was not a significant predictor of post-treatment potency on Pearson Chi-Square analysis. Conclusions: This represents the largest series evaluating the clinical outcome of SV implantation during low dose rate brachytherapy for patients with intermediate and high risk prostate cancer. SV implantation does not portend for improved biochemical control in this patient cohort. Despite this, it can be performed safely, with no significant increase in long-term rectal toxicity or erectile dysfunction. Author Disclosure: S.R. Blacksburg: None. N.N. Stone: G. Consultant; Amgen, Ferring, Janssen, Diversified Conference Management, Prologics LLC, Niohn MediPhysics. R.G. Stock: None.
309 Seminal Vesicle Implantation Does Not Significantly Affect Prostate Cancer Treatment-Related Outcomes S.R. Blacksburg, N.N. Stone, and R.G. Stock; Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): Implantation of the seminal vesicles (SVs) with brachytherapy is routinely performed at some high volume institutions. There is a small body of literature to suggest that implantation of the SVs is safe. Despite this, evaluation of the clinical benefit is lacking, with a paucity of data to reflect improvement in PSA failure or prevention of distant disease. This study reports the effect of implantation of the SVs for patients that have undergone definitive radiation for intermediate or high risk prostate cancer. Materials/Methods: Between June 1990 and March 2011, 1397 intermediate and high risk patients with prostate cancer were treated with low dose rate brachytherapy involving either I-125 or Pd-103, with 916 patients also receiving supplemental external beam radiation (median dose 4500 cGy). Four hundred eighteen of these patients received implantation of the SVs as a component of their brachytherapy treatment. Patients were divided into prognostic risk groups based on the National Comprehensive Cancer Network of intermediate in 51.8%, and high in 48.2%. The median followup for the entire cohort was 6.6 years (range, 2-19.2 years). Pre-treatment PSA was 0.8 - 300 ng/mL (median 8.8). Gleason scores were 6 in 36.1%, 7 in 44.2%, and 8-10 in 19.7%. Assuming an alpha beta ratio of 2, patients were treated with a BED of 90.9-299.2 Gy2 (median 200.0 Gy2). The Phoenix definition of PSA failure was used. Results: The overall freedom from PSA failure (FPF) at 5 years for patients with and without implanted SVs were 94.5% and 90.8% (p Z 0.01) and at 10 years remained marginally impactful at 83.2% and
310 Combined High-Dose-Rate (HDR) Brachytherapy and External Beam Radiation Therapy (EBRT) for Prostate Cancer: 5- and 10-Year Outcomes of Protocols 1 Versus 2 R. Galalae,1 N.H. Zakikhany,1 F. Geiger,2 F. Siebert,3 A. Nebelin,1 and B. Kimmig3; 1Medical Faculty, Christian-Albrechts-University, Kiel, Germany, 2Department of Pediatrics, Christian-Albrechts-University, Kiel, Germany, 3Clinic for Radiotherapy, Christian-Albrechts-University, Kiel, Germany Purpose/Objective(s): Dose escalation using HDR-brachytherapy is an established treatment method. First long-term results of the specific Kielmethod were previously published and documented excellent outcomes. This study aimed to evaluate the 5/10-years results of Kiel protocol 1 (1986-1992) in comparison with the successor protocol 2 (1992-1999). Materials/Methods: Conformal EBRT was delivered to the pelvis (50 Gy/ conventional fractionation) along with a HDR prostate-boost for a combined biologic equivalent dose of 242 Gy (a/b Z 1.5). The HDRbrachytherapy was performed in unchanged form in both protocols. Technical/logistical details are given in the first publication in 2002. The EBRT-CTV covered in protocol 1 the full pelvis, while it was reduced in protocol 2 to the small pelvis. Total dose and daily fractionation remained unchanged. Both cohorts counted 122 patients (n Z 244). The reported endpoints were overall survival, cancer-specific survival, local recurrence/ distant metastases rates, and biochemical control rate according to ASTRO/Phoenix definitions. All endpoints were calculated using the Kaplan-Meier method, and log-rank test when comparing the Kiel protocols 1 and 2. Results: Mean follow-up time was 93.5 months. The 5-year/10-year survival rates were in protocol 1 81%/62.1% for overall survival (OS), 92%/83.1% for cancer-specific survival (CSS), 92.5%/92.5%for local recurrence-free survival (LR), and 83.8%/82.8% for distant metastasis-free survival (DM), respectively. The 5/10-year rates in protocol 2 of OS, CSS, LR, and DM were 80.2%/56.8%, 93%/74.1%, 88.5%/86.7%, and 88%/ 72% respectively. Significant differences between the treatment protocols for these endpoints could not be identified. In addition, the 5/10-year results were not statistically significant different, when stratified for biochemical tumor control following ASTRO/Phoenix definitions for the non-high-risk group (low and intermediate risk combined): 81.6%/74.2% in protocol 1 and 83.2%/ 77.2% in protocol 2 for ASTRO, and 80.1%/ 68.6% and 79.6%/70.7% for Phoenix. In the high-risk patient group, however, the biochemical control at 5/10 years was both according to ASTRO (75%/72.3% vs 58.2%/44.8%; p Z 0.02), and Phoenix (71.7%/ 66.9% vs 61.7%/32.3%; p Z 0.03) significantly reduced in protocol 2 versus 1. Conclusions: Long-term results in all endpoints continue to demonstrate excellent values for the combination of HDR-brachytherapy/EBRT, which
306 Cell Cycle Progression (CCP) Score Significantly Predicts PSA Failure After EBRT J.K. Salama,1 S. Freedland,2 L. Gerber,2 J. Reid,3 W. Welbourn,3 A. Gutin,3 Z. Sangale,3 M. Brawer,3 and S. Stone3; 1Duke University, Durham, NC, 2Durham VA Medical Center and Duke University School of Medicine, Durham, NC, 3Myriad Genetics, Inc., Salt Lake City, UT Purpose/Objective(s): Accurate risk stratification is crucial to aid appropriate decision making in localized prostate cancer. To address this need, we have developed the Cell Cycle Progression (CCP) score, based on the collective gene expression of 31 cell cycle genes. To date, this score has been shown to not only predict BCR after prostatectomy, but also prostate cancer specific mortality in men undergoing observation in the United Kingdom. However, the value of this score based upon needle biopsies in men undergoing primary EBRT is untested. Materials/Methods: The CCP score was evaluated retrospectively in 152 patients treated with EBRT. Inclusion criteria were disease diagnosis from 1991 to 2006 and available biopsy tissue. Approximately half of the cohort was African-American. CCP score was derived from diagnostic biopsy. Outcome was time from EBRT to biochemical recurrence (BCR) using Phoenix definition, and median follow-up for patients without BCR was 5 years. Of the 152 initially selected patients, 6 were excluded due to delayed treatment (> 2 years from diagnosis) and 5 generated poor quality CCP scores, leaving 141 patients for analysis. Association with outcome was evaluated by CoxPH survival analysis and likelihood ratio tests. Results: Patient data was censored at 5-years of follow-up, 16 patients (11%) had BCR. The median CCP score was 0.12(IQR -0.43 to 0.66). In univariate analysis, CCP score was the most significant prognostic variable (p-value Z 0.002). The hazard ratio (HR) for BCR was 2.71 (95% CI, 1.44, 5.09) for a one-unit increase in CCP score. In a predefined multivariate analysis that included Gleason score, PSA, and percent positive cores, the HR for CCP remained largely unchanged (HR per CCP unit 2.53 (95% CI, 1.14, 5.61; p-value Z 0.019) demonstrating that CCP provides prognostic information that is largely not provided by clinical parameters. There was no evidence for interaction between CCP and any clinical variable, including ethnicity. Conclusions: We have evaluated the prognostic utility of CCP score for predicting BCR after EBRT. The CCP score was strongly associated with BCR and provided prognostic information beyond what is available from clinical parameters. If these results are validated in a larger cohort, then CCP score could be used to select high-risk men undergoing EBRT who may need combination therapy for their clinically localized prostate cancer. Author Disclosure: J.K. Salama: None. S. Freedland: None. L. Gerber: None. J. Reid: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. W. Welbourn: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. A. Gutin: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. Z. Sangale: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. M. Brawer: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc. S. Stone: A. Employee; Myriad Genetics, Inc. K. Stock; Myriad Genetics, Inc.
307 Validation of a Genomic Classifier That Predicts Metastatic Disease Progression in Men With Biochemical Recurrence Post-Radical Prostatectomy F.Y. Feng,1 M. Ghadessi,2 E. Davicioni,2 A. Crisan,2 N. Erho,2 A.P. Mitra,3 T.J. Triche,2 R.B. Jenkins,4 A.E. Ross,4 and E.M. Schaeffer4; 1University of Michigan, Ann Arbor, MI, 2GenomeDx Biosciences, Vancouver, BC, Canada, 3University of Southern California, Los Angeles, CA, 4Johns Hopkins Medical Institute, Baltimore, MD Purpose/Objective(s): Almost 50,000 men per year will present with biochemical recurrence (BCR) following local treatment for prostate cancer. These men with rising PSAs as the lone indicator of recurrence present a management dilemma due to their varied outcomes, as only
Oral Scientific Sessions S125 a proportion subsequently develop metastatic disease. Thus, there is a clear need to improve patient risk stratification in this context. Here, we evaluate a genomic classifier (GC) in men with BCR following radical prostatectomy (RP) for its ability to predict metastasis. Materials/Methods: The 22-marker GC was validated in a prospectively designed case-cohort study of 1,010 clinically high-risk RP patients. Two hundred nineteen patients, including 85 who developed BCR at least 6 months post-RP were subjected to microarray analysis and GC scores were generated. Survival ROC curves, weighted Cox proportional hazards, and decision curves were used to compare the performance of the GC to Gleason score (GS), PSA doubling time (PSAdT) and time to BCR (ttBCR). Results: Of the 85 patients with BCR after RP, 46% had a low GC score and 54% had a high score (using a pre-specified cut point of 0.4 identified during previous development of the GC panel.) GC scores significantly stratified men with BCR into those who would or would not develop subsequent metastasis. Forty percent of patients with a high GC score (versus 8% with a low GC score) developed metastasis at 3 years following BCR depending on GC score category, p < 0.001). The AUC (for prediction of subsequent metastases) was 0.82 (95% CI, 0.76-0.86) for GC, compared to 0.64 (0.58-0.70) for GS, 0.69 (0.61-0.77) for PSAdT and 0.52 (0.46-0.59) for ttBCR. In decision curve analysis, the GC had the highest overall net benefit, and in multivariable modeling with clinicopathologic variables, only GC (p Z 0.006) and GS (p Z 0.046) scores were significant predictors of metastasis. Conclusions: When compared to clinicopathologic variables, the GC better predicted metastatic progression among men with BCR following RP. While confirmatory studies in additional patient populations are required, these results suggest that use of the GC can allow for better selection of men requiring intensification of therapy, such as the addition of androgen deprivation therapy to salvage radiation, at the time of BCR. These results also support the rationale for further efforts to identify genomic-based prognostic or predictive factors in patients treated with radiation therapy for prostate cancer. Author Disclosure: F.Y. Feng: None. C. Buerki: A. Employee; GenomeDx Biosciences. M. Ghadessi: A. Employee; GenomeDx Biosciences. E. Davicioni: A. Employee; GenomeDx Biosciences. K. Stock; GenomeDx Biosciences. Q. Leadership; GenomeDx Biosciences. A. Crisan: A. Employee; GenomeDx Biosciences. N. Erho: A. Employee; GenomeDx Biosciences. A.P. Mitra: None. T.J. Triche: A. Employee; GenomeDx Biosciences. K. Stock; GenomeDx Biosciences. Q. Leadership; GenomeDx Biosciences. A.E. Ross: None. E.M. Schaeffer: None.
308 Serum Testosterone Changes in Patients Treated With Radiation Therapy Alone for Prostate Cancer on RTOG 9408 R. Nichols,1 A. George,2 J. Bahary,3 K.L. Zeitzer,4 L. Souhami,5 M.H. Leibenhaut,6 M. Rotman,7 E.M. Gore,8 A.G. Balogh,9 and C.U. Jones6; 1University of Florida Proton Therapy Institute, Jacksonville, FL, 2RTOG Statistical Center, Philadelphia, PA, 3Centre Hospitalier de l‘Universite´ de Montre´al-Notre Dame, Montreal, QC, Canada, 4Albert Einstein Cancer Center, Philadelphia, PA, 5McGill University, Montreal, QC, Canada, 6Radiological Associates of Sacramento, Sacramento, CA, 7Brooklyn MB-CCOP/SUNY Downstate, New York, NY, 8Medical College of Wisconsin, Milwaukee, WI, 9Tom Baker Cancer Centre, Calgary, AB, Canada Purpose/Objective(s): In light of studies suggesting that radiation therapy (XRT) may influence serum testosterone (ST) levels for patients treated for localized prostate cancer, we reviewed data on testosterone changes for patients treated with XRT alone on RTOG 9408. Materials/Methods: Patients enrolled on RTOG 9408 (T1b-T2b, PSA < 20 ng/mL) were randomized between XRT alone and XRT plus 4 months of total androgen ablation. XRT consisted of either whole pelvic radiation therapy to 46.8 Gy plus a 19.8 Gy prostate boost for a total dose of 66.6 Gy (WPRT) or treatment to the prostate alone for a total dose of 68.4 Gy (PORT). Most patients received WPRT. Only patients with the
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lowest risk features (PSA < 10 ng/mL and Gleason score 5 or a negative lymph node dissection) were assigned to receive PORT. XRT was delivered at 1.8 Gy per fraction. For this analysis, ST levels were investigated at the following collection periods: at study enrollment; completion of XRT; and at first follow-up 3 months after completion of XRT. The Wilcoxon signed rank test was used to compare change in pre and post treatment ST levels in patients who were randomized to the XRT alone arm. Results: Two thousand twenty-eight patients were enrolled on RTOG 9408. Nine hundred ninety-two were randomized to receive XRT alone. Nine hundred four (91%) of these patients had baseline ST values available and completed XRT. Of these 904, immediate and 3 month post XRT testosterone levels were available for 768 and 553 respectively. Excluding 10 patients who received hormonal therapy off protocol, 766 and 543 respectively, were analyzed. Pre-treatment median testosterone level for all patients was 370 ng/dL (P5-P95 Z 167 to 926) which did not differ significantly between the WPRT and PORT groups. For the entire group, at completion of XRT (median Z -26 ng/dL, P5-P95 Z -310 to 360; p < 0.01) and at the 3 month follow-up (median Z -33 ng/dL, P5-P95 Z -300 to 238; p < 0.01), median change in ST showed a statistically significant trend, indicating a decrease in ST level from baseline. For evaluable patients treated with WPRT (679 at end of XRT and 476 at 3-month follow-up), median change in ST is -29 ng/dL (P5-P95 Z -365 to 452; p < 0.01) and -33 ng/dL (P5-P95 Z -313 to 245; p < 0.01), respectively. Patients treated with PORT (87 at end of XRT and 67 at 3-month followup), median change in ST is -12 ng/dL (P5-P95 Z -202 to 101; p Z 0.01) and -37 ng/dL (P5-P95 Z -240 to 110; p < 0.01), respectively. Conclusions: XRT for prostate cancer, as delivered on RTOG 9408, was associated with statistically significant change in ST, indicating a decline. This may be secondary to scatter radiation to the Leydig cells. We have no evidence that these changes in ST have any direct impact on PSA control rates or on post treatment quality of life. Acknowledgment: This project was supported by RTOG grant U10 CA21661, and CCOP grant U10 CA37422 from the National Cancer Institute (NCI). Author Disclosure: R. Nichols: None. A. George: None. J. Bahary: None. K.L. Zeitzer: None. L. Souhami: None. M.H. Leibenhaut: None. M. Rotman: None. E.M. Gore: None. A.G. Balogh: None. C.U. Jones: None.
82% (p Z .04), respectively. On multivariate analysis, SV implantation lost its significant effect with only Androgen Deprivation use (p Z .01) and total BED (p < .0001) predictive of biochemical control as well as Gleason Score (p Z .009), initial PSA (p Z .006), and NCCN risk grouping (p Z .006). The 5 year freedom from rectal bleeding was equivalent between those with implanted SVs and those without (94 and 93.5%, respectively). Of the 916 men with full potency at baseline, 255 (27.8%) were no longer potent at last follow-up. SV implantation was not a significant predictor of post-treatment potency on Pearson Chi-Square analysis. Conclusions: This represents the largest series evaluating the clinical outcome of SV implantation during low dose rate brachytherapy for patients with intermediate and high risk prostate cancer. SV implantation does not portend for improved biochemical control in this patient cohort. Despite this, it can be performed safely, with no significant increase in long-term rectal toxicity or erectile dysfunction. Author Disclosure: S.R. Blacksburg: None. N.N. Stone: G. Consultant; Amgen, Ferring, Janssen, Diversified Conference Management, Prologics LLC, Niohn MediPhysics. R.G. Stock: None.
309 Seminal Vesicle Implantation Does Not Significantly Affect Prostate Cancer Treatment-Related Outcomes S.R. Blacksburg, N.N. Stone, and R.G. Stock; Mount Sinai School of Medicine, New York, NY Purpose/Objective(s): Implantation of the seminal vesicles (SVs) with brachytherapy is routinely performed at some high volume institutions. There is a small body of literature to suggest that implantation of the SVs is safe. Despite this, evaluation of the clinical benefit is lacking, with a paucity of data to reflect improvement in PSA failure or prevention of distant disease. This study reports the effect of implantation of the SVs for patients that have undergone definitive radiation for intermediate or high risk prostate cancer. Materials/Methods: Between June 1990 and March 2011, 1397 intermediate and high risk patients with prostate cancer were treated with low dose rate brachytherapy involving either I-125 or Pd-103, with 916 patients also receiving supplemental external beam radiation (median dose 4500 cGy). Four hundred eighteen of these patients received implantation of the SVs as a component of their brachytherapy treatment. Patients were divided into prognostic risk groups based on the National Comprehensive Cancer Network of intermediate in 51.8%, and high in 48.2%. The median followup for the entire cohort was 6.6 years (range, 2-19.2 years). Pre-treatment PSA was 0.8 - 300 ng/mL (median 8.8). Gleason scores were 6 in 36.1%, 7 in 44.2%, and 8-10 in 19.7%. Assuming an alpha beta ratio of 2, patients were treated with a BED of 90.9-299.2 Gy2 (median 200.0 Gy2). The Phoenix definition of PSA failure was used. Results: The overall freedom from PSA failure (FPF) at 5 years for patients with and without implanted SVs were 94.5% and 90.8% (p Z 0.01) and at 10 years remained marginally impactful at 83.2% and
310 Combined High-Dose-Rate (HDR) Brachytherapy and External Beam Radiation Therapy (EBRT) for Prostate Cancer: 5- and 10-Year Outcomes of Protocols 1 Versus 2 R. Galalae,1 N.H. Zakikhany,1 F. Geiger,2 F. Siebert,3 A. Nebelin,1 and B. Kimmig3; 1Medical Faculty, Christian-Albrechts-University, Kiel, Germany, 2Department of Pediatrics, Christian-Albrechts-University, Kiel, Germany, 3Clinic for Radiotherapy, Christian-Albrechts-University, Kiel, Germany Purpose/Objective(s): Dose escalation using HDR-brachytherapy is an established treatment method. First long-term results of the specific Kielmethod were previously published and documented excellent outcomes. This study aimed to evaluate the 5/10-years results of Kiel protocol 1 (1986-1992) in comparison with the successor protocol 2 (1992-1999). Materials/Methods: Conformal EBRT was delivered to the pelvis (50 Gy/ conventional fractionation) along with a HDR prostate-boost for a combined biologic equivalent dose of 242 Gy (a/b Z 1.5). The HDRbrachytherapy was performed in unchanged form in both protocols. Technical/logistical details are given in the first publication in 2002. The EBRT-CTV covered in protocol 1 the full pelvis, while it was reduced in protocol 2 to the small pelvis. Total dose and daily fractionation remained unchanged. Both cohorts counted 122 patients (n Z 244). The reported endpoints were overall survival, cancer-specific survival, local recurrence/ distant metastases rates, and biochemical control rate according to ASTRO/Phoenix definitions. All endpoints were calculated using the Kaplan-Meier method, and log-rank test when comparing the Kiel protocols 1 and 2. Results: Mean follow-up time was 93.5 months. The 5-year/10-year survival rates were in protocol 1 81%/62.1% for overall survival (OS), 92%/83.1% for cancer-specific survival (CSS), 92.5%/92.5%for local recurrence-free survival (LR), and 83.8%/82.8% for distant metastasis-free survival (DM), respectively. The 5/10-year rates in protocol 2 of OS, CSS, LR, and DM were 80.2%/56.8%, 93%/74.1%, 88.5%/86.7%, and 88%/ 72% respectively. Significant differences between the treatment protocols for these endpoints could not be identified. In addition, the 5/10-year results were not statistically significant different, when stratified for biochemical tumor control following ASTRO/Phoenix definitions for the non-high-risk group (low and intermediate risk combined): 81.6%/74.2% in protocol 1 and 83.2%/ 77.2% in protocol 2 for ASTRO, and 80.1%/ 68.6% and 79.6%/70.7% for Phoenix. In the high-risk patient group, however, the biochemical control at 5/10 years was both according to ASTRO (75%/72.3% vs 58.2%/44.8%; p Z 0.02), and Phoenix (71.7%/ 66.9% vs 61.7%/32.3%; p Z 0.03) significantly reduced in protocol 2 versus 1. Conclusions: Long-term results in all endpoints continue to demonstrate excellent values for the combination of HDR-brachytherapy/EBRT, which