- Email: [email protected]
A Family History of Prostate Cancer is not Associated with Poorer Outcomes following Radiotherapy
Proceedings of the 53rd Annual ASTRO Meeting
1114
Prognostic Significance of Histologically Proven Residual Tumor following Radical Radiotherapy
1,2
G. Ljung , A. Valachis1, A. Nearchou1, P. Lind1,3, S. Nilsson4 1
Department of Oncology, M€alarhospital, Eskilstuna, Sweden, 2University of Uppsala, Uppsala, Sweden, 3Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 4Radiumhemmet, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden Purpose/Objective(s): We investigated whether microscopic evidence of residual tumor following radical radiotherapy of prostatic carcinoma lead to a negative impact on prognosis and treatment outcome. Materials/Methods: During 1980 to 1989, 176 pats with clinically staged prostatic adenocarcinoma T1 – 3 N0 M0 were treated with radical radiotherapy (RRT) with 2.0 – 2.3 Gy /fraction, 4 – 5 times a week to 70 Gy (60 – 74 Gy). Out of the 70 surviving patients in 1992, 55 (79%) agreed to participate in a TRUS guided core needle biopsy mapping study for the assessment of local cure with an average follow-up of 6.8 years (3 – 12) after RRT. In 18 of the 55 biopsied patients (33%), endocrine treatment was implemented; in 6 cases prior to or concomitant with RRT and in 12 patients due to metastatic spread. Residual tumor was demonstrated in 67% (37/55) of the patients, while 33% (18/55) proved locally cured. A follow-up of the biopsied patients has now been performed, with a focus on disease progression and survival. Results: The median follow-up was 12 years (4.8 – 20.6) from the onset of RRT and 4.6 years (0.5 – 13.8) from the date of biopsy control. There was no difference in the follow-up time, initial T-Stage, tumor grade or dose-level between the biopsy-positive (B+) and biopsy-negative(B-) patients. The patients who proved histopathologically free of tumor (B-) showed a significantly longer overall survival (OS) compared to patients with residual tumor (B+); median OS from biopsy being 9.2 vs. 3.5 years (p = 0.04). A statistically proven higher cancer specific survival (CSS) as well as progression free survival (PFS) from biopsy was also noted for the Bas opposed to the B+ group; median CSS 9.3 vs. 3.5 years (p = 0.001) and median PFS 7.5 vs. 1.9 years (p = 0.002), respectively. Conclusions: We found a statistically significant correlation between residual, microscopically verified, prostate cancer and short CSS and short OS in patients with localized prostate cancer who received RRT. This study is, to our knowledge, the first to demonstrate that a total eradication of tumor cells have a significant impact on OS and disease progression after an observation period of more than 10 years after completion of radiation treatment. The data raise the question whether biopsy verified local cure is an even better outcome endpoint than biochemical (PSA) no-evidence-of-disease (bNED) in trials comparing different dose fractionation schedules and combination therapies with drugs. Author Disclosure: G. Ljung: None. A. Valachis: None. A. Nearchou: None. P. Lind: None. S. Nilsson: None.
1115
A Family History of Prostate Cancer is not Associated with Poorer Outcomes following Radiotherapy
H. P. Bagshaw1, K. Ruth2, E. M. Horwitz2, D. Chen2, M. K. Buyyounouski1 1
Temple University School of Medicine, Philadelphia, PA, 2Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s): Prostate cancer (PC) has a strong familial inheritance pattern. In some instances, family history (FH) is used to help guide treatment because it is thought to be a prognostic factor that represents severity of disease otherwise not represented by traditional risk factors including PSA, Gleason score (GS), and T-Stage. The purpose of this report is to examine FH as a prognostic factor following radiotherapy (RT) for PC. Materials/Methods: Risk of biochemical failure (BF, Nadir+2), distant metastasis (DM), cause specific mortality (CSM), and overall mortality (OM) for 1711 men treated with RT alone (median dose = 74 Gy; range, 70 – 80) between 1989 and 2007 were compared according to FH. Four hundred twenty-six patients treated during this same period with missing FH data were excluded. FH was defined as any prostate cancer in one or more first-degree relatives. Cox proportional hazards analysis was used for multivariable analysis in a model including GS (2 – 6 vs. 7 vs. 8 – 10), T-Stage (T1 vs. T2 vs. T3), PSA (continuous), RT dose (continuous), and FH (present vs. absent). For the BF outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for FH vs. none. Results: The median follow-up was 71 months (range, 1 to 215). The proportion of men with a FH present was 23%. Men with a positive FH were more likely to be younger (median age: 67.4 vs. 68.5, Wilcoxon p = 0.0499), have a lower PSA (median PSA: 6.0 vs. 6.4 ng/mL, Wilcoxon p = 0.0408) and non-palpable disease (T1: 67% vs. 58%, T2 32% vs. 38%, T3: 2% vs. 4%; chi-square p = 0.004). There was no significant difference in the distribution of GS (2 – 6, 7, 8 – 10) or PSA (20) based on FH. A positive FH was not an independent predictor of BF DM ,CSM, or OM (all p . 0.2 for FH) in multivariable analysis. The predictors for BF were GS (p \ 0.0001), T-Stage (p = 0.0004), PSA (p \ 0.0001), and RT dose (p = 0.03). The predictors for DM were GS (p \ 0.0001), T-Stage (p = 0.0002), and PSA (p \ 0.001). The predictors for CSS were GS (p = 0.02), T-Stage (p = 0.009), and PSA (p = 0.007). The predictors for OS were GS (p = 0.005) and RT dose (p = 0.003). Conclusions: This is the largest study of the influence of FH on outcomes following RT for prostate cancer, which shows a positive FH is not a reliable prognostic factor. A positive FH was however, associated with more favorable PSA values and T-Stage that may be the result of earlier screening. Family history should not be used in clinical practice as a prognostic factor until carefully designed prospective studies suggest otherwise. Author Disclosure: H.P. Bagshaw: None. K. Ruth: None. E.M. Horwitz: None. D. Chen: None. M.K. Buyyounouski: None.
1116
Androgen Deprivation Therapy in Conjunction with External Beam Radiotherapy Does Not Adversely Affect Long-term Cardiac Morbidity and Mortality among Patients Treated for Clinically Localized Prostate Cancer
M. J. Zelefsky, T. Zahra, X. Pei, Z. Zhang, Y. Yamada, M. Kollmeier, B. Cox Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): To determine the impact of neo-adjuvant and concurrent androgen deprivation therapy (ADT) on the risk of cardiac morbidity and mortality among patients with clinically localized prostate treated with high-dose external beam radiotherapy (EBRT).
S211
1114
Prognostic Significance of Histologically Proven Residual Tumor following Radical Radiotherapy
1,2
G. Ljung , A. Valachis1, A. Nearchou1, P. Lind1,3, S. Nilsson4 1
Department of Oncology, M€alarhospital, Eskilstuna, Sweden, 2University of Uppsala, Uppsala, Sweden, 3Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 4Radiumhemmet, Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden Purpose/Objective(s): We investigated whether microscopic evidence of residual tumor following radical radiotherapy of prostatic carcinoma lead to a negative impact on prognosis and treatment outcome. Materials/Methods: During 1980 to 1989, 176 pats with clinically staged prostatic adenocarcinoma T1 – 3 N0 M0 were treated with radical radiotherapy (RRT) with 2.0 – 2.3 Gy /fraction, 4 – 5 times a week to 70 Gy (60 – 74 Gy). Out of the 70 surviving patients in 1992, 55 (79%) agreed to participate in a TRUS guided core needle biopsy mapping study for the assessment of local cure with an average follow-up of 6.8 years (3 – 12) after RRT. In 18 of the 55 biopsied patients (33%), endocrine treatment was implemented; in 6 cases prior to or concomitant with RRT and in 12 patients due to metastatic spread. Residual tumor was demonstrated in 67% (37/55) of the patients, while 33% (18/55) proved locally cured. A follow-up of the biopsied patients has now been performed, with a focus on disease progression and survival. Results: The median follow-up was 12 years (4.8 – 20.6) from the onset of RRT and 4.6 years (0.5 – 13.8) from the date of biopsy control. There was no difference in the follow-up time, initial T-Stage, tumor grade or dose-level between the biopsy-positive (B+) and biopsy-negative(B-) patients. The patients who proved histopathologically free of tumor (B-) showed a significantly longer overall survival (OS) compared to patients with residual tumor (B+); median OS from biopsy being 9.2 vs. 3.5 years (p = 0.04). A statistically proven higher cancer specific survival (CSS) as well as progression free survival (PFS) from biopsy was also noted for the Bas opposed to the B+ group; median CSS 9.3 vs. 3.5 years (p = 0.001) and median PFS 7.5 vs. 1.9 years (p = 0.002), respectively. Conclusions: We found a statistically significant correlation between residual, microscopically verified, prostate cancer and short CSS and short OS in patients with localized prostate cancer who received RRT. This study is, to our knowledge, the first to demonstrate that a total eradication of tumor cells have a significant impact on OS and disease progression after an observation period of more than 10 years after completion of radiation treatment. The data raise the question whether biopsy verified local cure is an even better outcome endpoint than biochemical (PSA) no-evidence-of-disease (bNED) in trials comparing different dose fractionation schedules and combination therapies with drugs. Author Disclosure: G. Ljung: None. A. Valachis: None. A. Nearchou: None. P. Lind: None. S. Nilsson: None.
1115
A Family History of Prostate Cancer is not Associated with Poorer Outcomes following Radiotherapy
H. P. Bagshaw1, K. Ruth2, E. M. Horwitz2, D. Chen2, M. K. Buyyounouski1 1
Temple University School of Medicine, Philadelphia, PA, 2Fox Chase Cancer Center, Philadelphia, PA
Purpose/Objective(s): Prostate cancer (PC) has a strong familial inheritance pattern. In some instances, family history (FH) is used to help guide treatment because it is thought to be a prognostic factor that represents severity of disease otherwise not represented by traditional risk factors including PSA, Gleason score (GS), and T-Stage. The purpose of this report is to examine FH as a prognostic factor following radiotherapy (RT) for PC. Materials/Methods: Risk of biochemical failure (BF, Nadir+2), distant metastasis (DM), cause specific mortality (CSM), and overall mortality (OM) for 1711 men treated with RT alone (median dose = 74 Gy; range, 70 – 80) between 1989 and 2007 were compared according to FH. Four hundred twenty-six patients treated during this same period with missing FH data were excluded. FH was defined as any prostate cancer in one or more first-degree relatives. Cox proportional hazards analysis was used for multivariable analysis in a model including GS (2 – 6 vs. 7 vs. 8 – 10), T-Stage (T1 vs. T2 vs. T3), PSA (continuous), RT dose (continuous), and FH (present vs. absent). For the BF outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for FH vs. none. Results: The median follow-up was 71 months (range, 1 to 215). The proportion of men with a FH present was 23%. Men with a positive FH were more likely to be younger (median age: 67.4 vs. 68.5, Wilcoxon p = 0.0499), have a lower PSA (median PSA: 6.0 vs. 6.4 ng/mL, Wilcoxon p = 0.0408) and non-palpable disease (T1: 67% vs. 58%, T2 32% vs. 38%, T3: 2% vs. 4%; chi-square p = 0.004). There was no significant difference in the distribution of GS (2 – 6, 7, 8 – 10) or PSA (20) based on FH. A positive FH was not an independent predictor of BF DM ,CSM, or OM (all p . 0.2 for FH) in multivariable analysis. The predictors for BF were GS (p \ 0.0001), T-Stage (p = 0.0004), PSA (p \ 0.0001), and RT dose (p = 0.03). The predictors for DM were GS (p \ 0.0001), T-Stage (p = 0.0002), and PSA (p \ 0.001). The predictors for CSS were GS (p = 0.02), T-Stage (p = 0.009), and PSA (p = 0.007). The predictors for OS were GS (p = 0.005) and RT dose (p = 0.003). Conclusions: This is the largest study of the influence of FH on outcomes following RT for prostate cancer, which shows a positive FH is not a reliable prognostic factor. A positive FH was however, associated with more favorable PSA values and T-Stage that may be the result of earlier screening. Family history should not be used in clinical practice as a prognostic factor until carefully designed prospective studies suggest otherwise. Author Disclosure: H.P. Bagshaw: None. K. Ruth: None. E.M. Horwitz: None. D. Chen: None. M.K. Buyyounouski: None.
1116
Androgen Deprivation Therapy in Conjunction with External Beam Radiotherapy Does Not Adversely Affect Long-term Cardiac Morbidity and Mortality among Patients Treated for Clinically Localized Prostate Cancer
M. J. Zelefsky, T. Zahra, X. Pei, Z. Zhang, Y. Yamada, M. Kollmeier, B. Cox Memorial Sloan-Kettering Cancer Center, New York, NY Purpose/Objective(s): To determine the impact of neo-adjuvant and concurrent androgen deprivation therapy (ADT) on the risk of cardiac morbidity and mortality among patients with clinically localized prostate treated with high-dose external beam radiotherapy (EBRT).
S211