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Long-Term Prostate-Specific Antigen Stability and Predictive Factors of Failure After Permanent Seed Prostate Brachytherapy
Oral Scientific Sessions S137
Volume 96 Number 2S Supplement 2016 Author Disclosure: W.F. Hartsell: Employee; Cadence Health. Partner; Radiation Oncology Consultants, Ltd. Partnership; CPTI, Illinois CyberKnife, Elk Grove Radiosurgery. Oversight; National Association for Proton Therapy. Leadership; Proton Collaborative Group. D. Godes: Consultant; National Association for Proton Therapy. T.D. Ketch: None. J. Caron: Consultant; National Association for Proton Therapy. J.M. Metz: None. M.P. Mehta: None.
308 Long-Term Prostate-Specific Antigen Stability and Predictive Factors of Failure After Permanent Seed Prostate Brachytherapy A. Tetreault,1 J.M. Crook,1 J. Hamm,2 T. Pickles,3 M. Keyes,3 M. McKenzie,3 H.H. Pai,4 F. Bachand,1 and W.J. Morris5; 1BC Cancer Agency, Kelowna, BC, Canada, 2British Columbia Cancer Agency, Vancouver, BC, Canada, 3BC Cancer Agency, Vancouver, BC, Canada, 4 BC Cancer Agency, Surrey, BC, Canada, 5BC Cancer Agency, Vancouver, BC, Canada Purpose/Objective(s): The Phoenix definition of biochemical failure (BF) (nadir + 2) may overestimate cure rates after low dose rate prostate brachytherapy (LDR-PB). The purpose of this study is to assess long term PSA stability after LDR-PB and predictive factors of eventual BF for those with a slowly rising PSA. Materials/Methods: A total of 2772 low or intermediate risk prostate cancers underwent Iodine-125 LDR-PB monotherapy between 1998 and 2010. Of the patients, 49.7% received androgen deprivation (ADT) prior to LDR-PB (treatment policy: 6 months). Patients with <36 months follow-up were excluded (n Z 433). Clinical characteristics, dosimetric parameters, and sequential PSA readings were retrieved from a prospective database. A rising PSA was considered to be PSA 0.2 ng/mL with an increase 0.1 ng/mL over previous 2 years. The Phoenix definition was used to identify BF. Patients were classified as (1) stable PSA (cured), (2) rising PSA (without BF), or (3) BF. The three groups were compared according to clinical, dosimetric, and post-treatment parameters. Multivariate analysis was performed on the cured and failed groups to determine variables predicting for failure. Logistic regression model was applied with cross validation to test for model accuracy. ROC curves were obtained for patients with and without ADT to determine predictive cut-offs for BF. Results: Median follow-up is 89 months (37-199); median age at implant 66 years (43-84). Majority of patients (80.7%) had clinical stage T1-T2a, 55% had Gleason score 6 and median baseline PSA was 6.5 ng/ mL(0.3-40 ng/mL). Fifty-nine percent were intermediate risk. Among the 2339 patients analyzed, 2004 (85.7%) had a stable PSA and were considered cured [median PSA at 60 months (PSA-60): 0.04 ng/mL], 145 (6.2%) had a rising PSA (PSA-60: 0.27 ng/mL) and 190 (8.1%) had BF. PSA nadirs for the 3 groups were respectively 0.03 (cured), 0.16 (rising PSA), and 0.51 ng/mL (BF) (P < 0.0001). For patients with no prior ADT, the variables associated with failure are PSA nadir (OR Z 20.6, P < 0.0001) and PSA-60 (OR Z 18.3, P < 0.0001). If the model is applied to the rising PSA group, using a PSA-60 cut-off of 0.3 ng/mL (sensitivity: 85%, specificity: 98.1%), the risk of failure is 9.8% (8/82). For patients who received ADT, the predictive factors of failure are PSA60 (OR Z 53.9, P < 0.0001) and T-stage (OR Z 0.25, P Z 0.0008). Using this model and a PSA-60 cut-off of 0.1ng/mL (sensitivity: 85%, specificity: 92.9%), the predicted risk of BF in the rising PSA group is 53.7% (36/56). Taking into account the two predictive models, the anticipated cure rate for the entire cohort is 89.7%. Conclusion: Patients treated with LDR-PB monotherapy and whose PSA60 is 0.3 ng/mL are highly likely to be cured even if they experienced a slight PSA rise. However, for patients who also received ADT, a stricter cut-off of 0.1 ng/mL may be appropriate.
Author Disclosure: A. Tetreault: None. J.M. Crook: Employee; BC Cancer Agency. Honoraria; Astellas, Abbvie. Consultant; Breast micoseed. Research; Ferring. member; ASCO. J. Hamm: None. T. Pickles: Employee; BC Centre for Disease Control. Honoraria; Astra-Zeneca. Advisory Board; Bayer Pharma. M. Keyes: None. M. McKenzie: Independent Contractor; BC Cancer Agency. Honoraria; Johnson and Johnson. H.H. Pai: Stock; TelMedIG. speaker; Canadian Urological Association. Advise on center’s function and roles for its clients; Island Prostate Centre. F. Bachand: Independent Contractor; BC Cancer Agency. Honoraria; Bayer. Leader of the Radiation Oncology Department; BC Cancer Agency. W. Morris: None.
309 Local Recurrence Confirmed by Mapping Biopsy Following I-125 Prostate Brachytherapy With or Without External Beam Radiation Therapy A. Yorozu,1 R. Kota,1 Y. Takagawa,1 S. Saito,1 K. Toya,1 and Y. Shiraishi2; 1 Tokyo Medical Center, Tokyo, Japan, 2Keio University School of Medicine, Tokyo, Japan Purpose/Objective(s): To study patterns of failure using cases of local recurrence confirmed by mapping biopsy after I-125 prostate brachytherapy (BT). Materials/Methods: We retrospectively and comprehensively analyzed patterns of failure for a cohort of 1780 consecutive patients with localized prostate cancer receiving I-125 BT with or without supplemental external beam radiotherapy (EBRT) from 2003 to 2011. A total of 985 men were treated with BT, and 785 men were treated with BT combined with EBRT. The prescription dose was 110 Gy with EBRT or 145 Gy without EBRT, and D90 was 110e130% of the prescribed dose. For post-implant dosimetric analysis, a CT scan was obtained one month after implantation. Groups of 601, 970, and 209 men were categorized as low-, intermediate-, and high-risk, respectively, according to National Comprehensive Cancer Network. In total, 41% of patients received neoadjuvant androgen deprivation therapy. Biochemical failure was determined by the Phoenix definition. Imaging studies following biochemical failure were obtained sequentially by body CT scan and bone scan, or PET-CT scan. Finally transperineal template-guided mapping prostate biopsy was performed, and the studies were repeated until intervention started. The median of the biopsy cores was 33 (range, 20-64). Among patients with definitive biochemical failure, local recurrence was defined as a final positive posttreatment biopsy. The time to local recurrence was calculated by KaplanMeier method. The biological effective dose (BED) was calculated using an a/b of 2. Comparisons were made by log-rank test, and Cox proportional hazards model was used. Results: The median follow-up was 7 years (range, 2-14 years); 130 out of 1780 men (7.3%) developed biochemical failure. Biopsies were performed in 96 of the 130 cases (74%) with failure; in which 31 (32%) were positive and 65 were negative. For men whose biopsies were positive and negative, the median BED was 191 Gy2 and 210 Gy2 (P < 0.001), respectively. In univariate analysis, lower BED and no EBRT were associated with positive results. Factors such as age, initial PSA, T-stage, Gleason score, neoadjuvant androgen deprivation, PSA doubling time were not associated with positive results. In multivariate analysis, only BED was significant for positive biopsy. Of 130 men with failure, anatomical recurrent sites were identified in 88 cases. In the remaining 42 men with failure, a site of recurrence could not be identified in 35, and 7 received no investigations. Of the 25 men with local recurrence alone, 13 received local salvage treatment (re-BT in 12, and surgery in one). Conclusion: At least 31 out of 1780 (1.74%) patients developed local recurrence. About one third of patients with biochemical failure had a component of local recurrence. BED may predict local recurrence in patients with biochemical failure. Longer-term and more through follow-ups are needed to identify local recurrence without extraprostatic components in order to consider relevant salvage options.
Volume 96 Number 2S Supplement 2016 Author Disclosure: W.F. Hartsell: Employee; Cadence Health. Partner; Radiation Oncology Consultants, Ltd. Partnership; CPTI, Illinois CyberKnife, Elk Grove Radiosurgery. Oversight; National Association for Proton Therapy. Leadership; Proton Collaborative Group. D. Godes: Consultant; National Association for Proton Therapy. T.D. Ketch: None. J. Caron: Consultant; National Association for Proton Therapy. J.M. Metz: None. M.P. Mehta: None.
308 Long-Term Prostate-Specific Antigen Stability and Predictive Factors of Failure After Permanent Seed Prostate Brachytherapy A. Tetreault,1 J.M. Crook,1 J. Hamm,2 T. Pickles,3 M. Keyes,3 M. McKenzie,3 H.H. Pai,4 F. Bachand,1 and W.J. Morris5; 1BC Cancer Agency, Kelowna, BC, Canada, 2British Columbia Cancer Agency, Vancouver, BC, Canada, 3BC Cancer Agency, Vancouver, BC, Canada, 4 BC Cancer Agency, Surrey, BC, Canada, 5BC Cancer Agency, Vancouver, BC, Canada Purpose/Objective(s): The Phoenix definition of biochemical failure (BF) (nadir + 2) may overestimate cure rates after low dose rate prostate brachytherapy (LDR-PB). The purpose of this study is to assess long term PSA stability after LDR-PB and predictive factors of eventual BF for those with a slowly rising PSA. Materials/Methods: A total of 2772 low or intermediate risk prostate cancers underwent Iodine-125 LDR-PB monotherapy between 1998 and 2010. Of the patients, 49.7% received androgen deprivation (ADT) prior to LDR-PB (treatment policy: 6 months). Patients with <36 months follow-up were excluded (n Z 433). Clinical characteristics, dosimetric parameters, and sequential PSA readings were retrieved from a prospective database. A rising PSA was considered to be PSA 0.2 ng/mL with an increase 0.1 ng/mL over previous 2 years. The Phoenix definition was used to identify BF. Patients were classified as (1) stable PSA (cured), (2) rising PSA (without BF), or (3) BF. The three groups were compared according to clinical, dosimetric, and post-treatment parameters. Multivariate analysis was performed on the cured and failed groups to determine variables predicting for failure. Logistic regression model was applied with cross validation to test for model accuracy. ROC curves were obtained for patients with and without ADT to determine predictive cut-offs for BF. Results: Median follow-up is 89 months (37-199); median age at implant 66 years (43-84). Majority of patients (80.7%) had clinical stage T1-T2a, 55% had Gleason score 6 and median baseline PSA was 6.5 ng/ mL(0.3-40 ng/mL). Fifty-nine percent were intermediate risk. Among the 2339 patients analyzed, 2004 (85.7%) had a stable PSA and were considered cured [median PSA at 60 months (PSA-60): 0.04 ng/mL], 145 (6.2%) had a rising PSA (PSA-60: 0.27 ng/mL) and 190 (8.1%) had BF. PSA nadirs for the 3 groups were respectively 0.03 (cured), 0.16 (rising PSA), and 0.51 ng/mL (BF) (P < 0.0001). For patients with no prior ADT, the variables associated with failure are PSA nadir (OR Z 20.6, P < 0.0001) and PSA-60 (OR Z 18.3, P < 0.0001). If the model is applied to the rising PSA group, using a PSA-60 cut-off of 0.3 ng/mL (sensitivity: 85%, specificity: 98.1%), the risk of failure is 9.8% (8/82). For patients who received ADT, the predictive factors of failure are PSA60 (OR Z 53.9, P < 0.0001) and T-stage (OR Z 0.25, P Z 0.0008). Using this model and a PSA-60 cut-off of 0.1ng/mL (sensitivity: 85%, specificity: 92.9%), the predicted risk of BF in the rising PSA group is 53.7% (36/56). Taking into account the two predictive models, the anticipated cure rate for the entire cohort is 89.7%. Conclusion: Patients treated with LDR-PB monotherapy and whose PSA60 is 0.3 ng/mL are highly likely to be cured even if they experienced a slight PSA rise. However, for patients who also received ADT, a stricter cut-off of 0.1 ng/mL may be appropriate.
Author Disclosure: A. Tetreault: None. J.M. Crook: Employee; BC Cancer Agency. Honoraria; Astellas, Abbvie. Consultant; Breast micoseed. Research; Ferring. member; ASCO. J. Hamm: None. T. Pickles: Employee; BC Centre for Disease Control. Honoraria; Astra-Zeneca. Advisory Board; Bayer Pharma. M. Keyes: None. M. McKenzie: Independent Contractor; BC Cancer Agency. Honoraria; Johnson and Johnson. H.H. Pai: Stock; TelMedIG. speaker; Canadian Urological Association. Advise on center’s function and roles for its clients; Island Prostate Centre. F. Bachand: Independent Contractor; BC Cancer Agency. Honoraria; Bayer. Leader of the Radiation Oncology Department; BC Cancer Agency. W. Morris: None.
309 Local Recurrence Confirmed by Mapping Biopsy Following I-125 Prostate Brachytherapy With or Without External Beam Radiation Therapy A. Yorozu,1 R. Kota,1 Y. Takagawa,1 S. Saito,1 K. Toya,1 and Y. Shiraishi2; 1 Tokyo Medical Center, Tokyo, Japan, 2Keio University School of Medicine, Tokyo, Japan Purpose/Objective(s): To study patterns of failure using cases of local recurrence confirmed by mapping biopsy after I-125 prostate brachytherapy (BT). Materials/Methods: We retrospectively and comprehensively analyzed patterns of failure for a cohort of 1780 consecutive patients with localized prostate cancer receiving I-125 BT with or without supplemental external beam radiotherapy (EBRT) from 2003 to 2011. A total of 985 men were treated with BT, and 785 men were treated with BT combined with EBRT. The prescription dose was 110 Gy with EBRT or 145 Gy without EBRT, and D90 was 110e130% of the prescribed dose. For post-implant dosimetric analysis, a CT scan was obtained one month after implantation. Groups of 601, 970, and 209 men were categorized as low-, intermediate-, and high-risk, respectively, according to National Comprehensive Cancer Network. In total, 41% of patients received neoadjuvant androgen deprivation therapy. Biochemical failure was determined by the Phoenix definition. Imaging studies following biochemical failure were obtained sequentially by body CT scan and bone scan, or PET-CT scan. Finally transperineal template-guided mapping prostate biopsy was performed, and the studies were repeated until intervention started. The median of the biopsy cores was 33 (range, 20-64). Among patients with definitive biochemical failure, local recurrence was defined as a final positive posttreatment biopsy. The time to local recurrence was calculated by KaplanMeier method. The biological effective dose (BED) was calculated using an a/b of 2. Comparisons were made by log-rank test, and Cox proportional hazards model was used. Results: The median follow-up was 7 years (range, 2-14 years); 130 out of 1780 men (7.3%) developed biochemical failure. Biopsies were performed in 96 of the 130 cases (74%) with failure; in which 31 (32%) were positive and 65 were negative. For men whose biopsies were positive and negative, the median BED was 191 Gy2 and 210 Gy2 (P < 0.001), respectively. In univariate analysis, lower BED and no EBRT were associated with positive results. Factors such as age, initial PSA, T-stage, Gleason score, neoadjuvant androgen deprivation, PSA doubling time were not associated with positive results. In multivariate analysis, only BED was significant for positive biopsy. Of 130 men with failure, anatomical recurrent sites were identified in 88 cases. In the remaining 42 men with failure, a site of recurrence could not be identified in 35, and 7 received no investigations. Of the 25 men with local recurrence alone, 13 received local salvage treatment (re-BT in 12, and surgery in one). Conclusion: At least 31 out of 1780 (1.74%) patients developed local recurrence. About one third of patients with biochemical failure had a component of local recurrence. BED may predict local recurrence in patients with biochemical failure. Longer-term and more through follow-ups are needed to identify local recurrence without extraprostatic components in order to consider relevant salvage options.