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Correlation Between PSA Bounce, Time to Nadir, and Biochemical Failure in Patients With Prostate Cancer Treated With a Combination of HDR-Brachytherapy and Hypofractionated External Beam Radiation Therapy
S404
International Journal of Radiation Oncology Biology Physics
the validation phase, a parallel multivariate linear regression was performed with a subset of 398 SNPs genotyped with prostate custom array. Four different genetic inheritance models were tested for each SNP: allelic, genotypic, dominant and recessive. Combined p values were calculated using Fisher’s method. Results: Median follow up for all patients was 75mos (range, 10-215mos). Ninety-five percent, 90%, 85%, and 72% of patients in the discovery cohort and 94%, 90%, 82%, and 73% of patients in the validation cohort attained a PSA nadir of < 0.5, < 0.3, < 0.2, and < 0.1ng/mL, respectively. Median post-treatment intervals to attain these PSA nadirs were comparable between cohorts and were 20mos (range, 0.6-116mos), 28mos (range, 0.6-116mos), 34mos (range, 0.6-116mos), and 41mos (range, 3118mos), respectively. In combined analysis of the discovery and validation cohorts, we identified several SNPs that were significantly associated with a rapid interval to PSA nadir (combined p values 10 7 to 10 4). Conclusions: We identified a panel of candidate SNPs that were strongly associated with time to PSA nadir following definitive prostate radiation therapy. Since the time to PSA nadir has been shown to be significantly associated with long-term clinical outcomes (e.g., freedom from biochemical failure and distant metastasis), our results suggest that at least some of these SNPs may be prognostically useful in the setting of prostate radiation therapy. Author Disclosure: E. Ko: None. S.L. Kerns: None. N.N. Stone: G. Consultant; Amgen; Ferring; Janssen. R.G. Stock: None. H. Ostrer: None. B.S. Rosenstein: None.
the absolute PSA at initiation of SRT significantly predicted for bPFS even when accounting for SVI, GS 8-10, and surgical margins. Author Disclosure: M.E. Shukla: None. M.C. Mir: None. A.J. Stephenson: None. K.L. Stephans: None. E.A. Klein: None. R.D. Tendulkar: None.
2493 Preradiation Therapy PSA Is Predictive of Biochemical Progressionfree Survival Following Postprostatectomy Salvage Radiation Therapy M.E. Shukla, M.C. Mir, A.J. Stephenson, K.L. Stephans, E.A. Klein, and R.D. Tendulkar; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): To examine biochemical outcomes in men treated with post-prostatectomy salvage radiation therapy (SRT). Materials/Methods: We reviewed an IRB-approved prospectively maintained database and identified 286 men with non-metastatic, prostate cancer (PCa) treated with radical prostatectomy (RP) followed by SRT from 1986-2011. Men with N1 disease or those receiving androgen deprivation therapy prior to prostatectomy or radiation therapy were excluded from this analysis. Biochemical failure (bF) after SRT was defined as any immediate rise in prostate specific antigen (PSA) above the pre-SRT PSA, a PSA of 0.2 ng/mL above the nadir, or initiation of ADT. Kaplan-Meier estimates of biochemical progression free survival (bPFS) were conducted. Cox-proportional hazard regression analysis was performed to examine the influence of clinical and pathologic features on bPFS in patients with pre-SRT PSA 0.5 ng/mL. Results: Median initial PSA was 7.0 ng/mL and median pre-SRT PSA was 0.49 ng/mL. Based on surgical pathology, 16% had Gleason score (GS) 6, 70% had GS 7, and 13% had GS 8-10. Surgical margins were positive (SM+) in 65%, extracapsular extension (ECE) in 61%, seminal vesicle invasion (SVI) in 15%. Overall 5-yr bPFS following SRT was 51% and median time to bF was 64 months. When stratified by pre-RT PSA, 5-yr bPFS for those with a PSA of 0.5 ng/mL was 61% (95% CI 51 - 71%), for 0.51 - 1.00 ng/mL was 49% (95% CI 36 - 63%), for 1.01 - 2.00 ng/mL was 45% (95% CI 24 - 66%), and for >2.00 ng/mL was 12% (95% CI 0 26%), p < 0.001. Among the 164 men with pre-SRT PSA 0.5 ng/mL, 109 had SM+, and 36 had GS 8-10 and/or SVI. On MVA, in this subset, SVI and/or GS 8-10 were predictive of bF following SRT (HR 2.26, p Z 0.008) as was pre-RT PSA (HR 18.6, p Z 0.028) and negative surgical margins (HR 2.0, p Z 0.04). Log2PSA was calculated and still remained a significant predictive factor for bPFS overall (HR 1.5, p < 0.001) and in the pre-SRT PSA 0.5 ng/mL subset. Conclusions: Overall, 51% of patients remained without evidence of biochemical progression following SRT at 5 years. Salvage radiation therapy initiated at lower PSA values resulted in improved biochemical progression free survival. Even at low pre-SRT PSA values, 0.5 ng/mL,
2494 Correlation Between PSA Bounce, Time to Nadir, and Biochemical Failure in Patients With Prostate Cancer Treated With a Combination of HDR-Brachytherapy and Hypofractionated External Beam Radiation Therapy N. Patel, F. Cury, L. Souhami, A. Aprikian, S. Faria, M. David, and M. Duclos; McGill University Health Centre, Montreal, QC, Canada Purpose/Objective(s): To report the frequency, timing and magnitude of PSA bounce (PB) in patients who have received HDR-brachytherapy (HDRB) plus hypofractionated external beam RT (HyRT) and to assess whether there is an association between PB, time to PSA nadir and biochemical failure (BF). Materials/Methods: One hundred fifteen patients with intermediate risk prostate cancer who received 10 Gy single fraction 192Ir HDRB followed by 50 Gy in 20 daily fractions of HyRT without androgen deprivation therapy between 2001 and 2009 were eligible for analysis. All patients had a minimum of 2 year follow-up with at least 4 PSA results. Median followup was 67 months. Patients who had BF within 2 years were excluded. PB was defined as PSA elevation >0.1ng/mL from previous measurement with subsequent drop to pre-bounce level. BF was defined as PSA nadir+ 2ng/mL. Results: Bounce occurred in 51(44%) patients with a median time to bounce 16.5 months and range of 3-76 months. The Table demonstrates the number of patients who had a PB at different cut-off levels. The median time to PSA normalization following a PB was 7 months (range, 2-32 months). The median magnitude of PB was 0.425ng/mL (range, 0.116.62). BF occurred in 13 (11%) patients, of whom 3 (23%) had a PB. The median magnitude of PB in these patients was 0.432ng/mL (range, 0.230.53). Median time to PB in BF group was 11 months and 17 months in non-BF group. Four patients (3.5%) in PB group fit the criteria for BF. The time to nadir in all patients was 52 months, 55.5 months for patients with a PB and 46 months for patients with no PB. The time to nadir in patients with BF was 28 months. The median nadir value was 0.17 but 0.685 in patients with BF. Conclusions: PB is common after HDRB and HyRT and can occur up to 76 months after treatment. It can rarely fit the criteria for BF. There is a lower incidence of BF (6%) in patients with a PB, but those that do fail have a shorter time to PB. An acknowledgement of this phenomenon should be made when interpreting PSA results during follow-up to prevent unnecessary interventions. Poster Viewing Abstract 2494; Table PSA Bounce Patient number
0.1 51 (44%)
0.2 46 (40%)
0.5 25(22%)
1 13 (11%)
2 4 (3.5%)
Author Disclosure: N. Patel: None. F. Cury: None. L. Souhami: None. A. Aprikian: None. S. Faria: None. M. David: None. M. Duclos: None.
2495 Long-term Follow-up of Combined Modality Therapy With Pelvic External Radiation Followed by Cs-131 Brachytherapy Boost in Men With High-Risk Prostate Cancer Y. Kwok, A. Saltos, D.H. Boggs, M. Naslund, A. Hussain, and P. Amin; University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): To report the mature results of an initial experience on high-risk prostate cancer patients treated with combined modality therapy (CMT) with androgen deprivation therapy (ADT), external beam radiation therapy (EBRT) and Cs-131 brachytherapy (BT) boost.
International Journal of Radiation Oncology Biology Physics
the validation phase, a parallel multivariate linear regression was performed with a subset of 398 SNPs genotyped with prostate custom array. Four different genetic inheritance models were tested for each SNP: allelic, genotypic, dominant and recessive. Combined p values were calculated using Fisher’s method. Results: Median follow up for all patients was 75mos (range, 10-215mos). Ninety-five percent, 90%, 85%, and 72% of patients in the discovery cohort and 94%, 90%, 82%, and 73% of patients in the validation cohort attained a PSA nadir of < 0.5, < 0.3, < 0.2, and < 0.1ng/mL, respectively. Median post-treatment intervals to attain these PSA nadirs were comparable between cohorts and were 20mos (range, 0.6-116mos), 28mos (range, 0.6-116mos), 34mos (range, 0.6-116mos), and 41mos (range, 3118mos), respectively. In combined analysis of the discovery and validation cohorts, we identified several SNPs that were significantly associated with a rapid interval to PSA nadir (combined p values 10 7 to 10 4). Conclusions: We identified a panel of candidate SNPs that were strongly associated with time to PSA nadir following definitive prostate radiation therapy. Since the time to PSA nadir has been shown to be significantly associated with long-term clinical outcomes (e.g., freedom from biochemical failure and distant metastasis), our results suggest that at least some of these SNPs may be prognostically useful in the setting of prostate radiation therapy. Author Disclosure: E. Ko: None. S.L. Kerns: None. N.N. Stone: G. Consultant; Amgen; Ferring; Janssen. R.G. Stock: None. H. Ostrer: None. B.S. Rosenstein: None.
the absolute PSA at initiation of SRT significantly predicted for bPFS even when accounting for SVI, GS 8-10, and surgical margins. Author Disclosure: M.E. Shukla: None. M.C. Mir: None. A.J. Stephenson: None. K.L. Stephans: None. E.A. Klein: None. R.D. Tendulkar: None.
2493 Preradiation Therapy PSA Is Predictive of Biochemical Progressionfree Survival Following Postprostatectomy Salvage Radiation Therapy M.E. Shukla, M.C. Mir, A.J. Stephenson, K.L. Stephans, E.A. Klein, and R.D. Tendulkar; Cleveland Clinic, Cleveland, OH Purpose/Objective(s): To examine biochemical outcomes in men treated with post-prostatectomy salvage radiation therapy (SRT). Materials/Methods: We reviewed an IRB-approved prospectively maintained database and identified 286 men with non-metastatic, prostate cancer (PCa) treated with radical prostatectomy (RP) followed by SRT from 1986-2011. Men with N1 disease or those receiving androgen deprivation therapy prior to prostatectomy or radiation therapy were excluded from this analysis. Biochemical failure (bF) after SRT was defined as any immediate rise in prostate specific antigen (PSA) above the pre-SRT PSA, a PSA of 0.2 ng/mL above the nadir, or initiation of ADT. Kaplan-Meier estimates of biochemical progression free survival (bPFS) were conducted. Cox-proportional hazard regression analysis was performed to examine the influence of clinical and pathologic features on bPFS in patients with pre-SRT PSA 0.5 ng/mL. Results: Median initial PSA was 7.0 ng/mL and median pre-SRT PSA was 0.49 ng/mL. Based on surgical pathology, 16% had Gleason score (GS) 6, 70% had GS 7, and 13% had GS 8-10. Surgical margins were positive (SM+) in 65%, extracapsular extension (ECE) in 61%, seminal vesicle invasion (SVI) in 15%. Overall 5-yr bPFS following SRT was 51% and median time to bF was 64 months. When stratified by pre-RT PSA, 5-yr bPFS for those with a PSA of 0.5 ng/mL was 61% (95% CI 51 - 71%), for 0.51 - 1.00 ng/mL was 49% (95% CI 36 - 63%), for 1.01 - 2.00 ng/mL was 45% (95% CI 24 - 66%), and for >2.00 ng/mL was 12% (95% CI 0 26%), p < 0.001. Among the 164 men with pre-SRT PSA 0.5 ng/mL, 109 had SM+, and 36 had GS 8-10 and/or SVI. On MVA, in this subset, SVI and/or GS 8-10 were predictive of bF following SRT (HR 2.26, p Z 0.008) as was pre-RT PSA (HR 18.6, p Z 0.028) and negative surgical margins (HR 2.0, p Z 0.04). Log2PSA was calculated and still remained a significant predictive factor for bPFS overall (HR 1.5, p < 0.001) and in the pre-SRT PSA 0.5 ng/mL subset. Conclusions: Overall, 51% of patients remained without evidence of biochemical progression following SRT at 5 years. Salvage radiation therapy initiated at lower PSA values resulted in improved biochemical progression free survival. Even at low pre-SRT PSA values, 0.5 ng/mL,
2494 Correlation Between PSA Bounce, Time to Nadir, and Biochemical Failure in Patients With Prostate Cancer Treated With a Combination of HDR-Brachytherapy and Hypofractionated External Beam Radiation Therapy N. Patel, F. Cury, L. Souhami, A. Aprikian, S. Faria, M. David, and M. Duclos; McGill University Health Centre, Montreal, QC, Canada Purpose/Objective(s): To report the frequency, timing and magnitude of PSA bounce (PB) in patients who have received HDR-brachytherapy (HDRB) plus hypofractionated external beam RT (HyRT) and to assess whether there is an association between PB, time to PSA nadir and biochemical failure (BF). Materials/Methods: One hundred fifteen patients with intermediate risk prostate cancer who received 10 Gy single fraction 192Ir HDRB followed by 50 Gy in 20 daily fractions of HyRT without androgen deprivation therapy between 2001 and 2009 were eligible for analysis. All patients had a minimum of 2 year follow-up with at least 4 PSA results. Median followup was 67 months. Patients who had BF within 2 years were excluded. PB was defined as PSA elevation >0.1ng/mL from previous measurement with subsequent drop to pre-bounce level. BF was defined as PSA nadir+ 2ng/mL. Results: Bounce occurred in 51(44%) patients with a median time to bounce 16.5 months and range of 3-76 months. The Table demonstrates the number of patients who had a PB at different cut-off levels. The median time to PSA normalization following a PB was 7 months (range, 2-32 months). The median magnitude of PB was 0.425ng/mL (range, 0.116.62). BF occurred in 13 (11%) patients, of whom 3 (23%) had a PB. The median magnitude of PB in these patients was 0.432ng/mL (range, 0.230.53). Median time to PB in BF group was 11 months and 17 months in non-BF group. Four patients (3.5%) in PB group fit the criteria for BF. The time to nadir in all patients was 52 months, 55.5 months for patients with a PB and 46 months for patients with no PB. The time to nadir in patients with BF was 28 months. The median nadir value was 0.17 but 0.685 in patients with BF. Conclusions: PB is common after HDRB and HyRT and can occur up to 76 months after treatment. It can rarely fit the criteria for BF. There is a lower incidence of BF (6%) in patients with a PB, but those that do fail have a shorter time to PB. An acknowledgement of this phenomenon should be made when interpreting PSA results during follow-up to prevent unnecessary interventions. Poster Viewing Abstract 2494; Table PSA Bounce Patient number
0.1 51 (44%)
0.2 46 (40%)
0.5 25(22%)
1 13 (11%)
2 4 (3.5%)
Author Disclosure: N. Patel: None. F. Cury: None. L. Souhami: None. A. Aprikian: None. S. Faria: None. M. David: None. M. Duclos: None.
2495 Long-term Follow-up of Combined Modality Therapy With Pelvic External Radiation Followed by Cs-131 Brachytherapy Boost in Men With High-Risk Prostate Cancer Y. Kwok, A. Saltos, D.H. Boggs, M. Naslund, A. Hussain, and P. Amin; University of Maryland School of Medicine, Baltimore, MD Purpose/Objective(s): To report the mature results of an initial experience on high-risk prostate cancer patients treated with combined modality therapy (CMT) with androgen deprivation therapy (ADT), external beam radiation therapy (EBRT) and Cs-131 brachytherapy (BT) boost.