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First Year PSA Kinetics and Nadirs After Prostate Cancer Radiotherapy Are Predictive of Overall Survival
Proceedings of the 47th Annual ASTRO Meeting
radiation dose to still be independent predictors of bF. However, RT technique was no longer significant. With either definition, on both univariate and multivariate analysis, radiation dose remained an independent predictor of biochemical failure. Conclusions: With changing definitions of bF, the results of failure analyses will change. In this large study sample with long median follow-up, the ASTRO definition resulted in worse bRFS rates earlier in the follow-up period (within the first 6 –7 years), while the nadir⫹2 definition resulted in worse outcomes later in the follow-up period (beyond 7– 8 years). Discrepancies in the results of the multivariate analyses were seen, such as radiation technique being significant in predicting bF with one definition (ASTRO), but not the other. Radiation dose, iPSA, bGS, and T stage remained important predictors of bF with either definition. On the basis of this analysis, no significant changes in the use of prognostic factors or treatment factors would be recommended.
Fig. 1
1091
First Year PSA Kinetics and Nadirs After Prostate Cancer Radiotherapy Are Predictive of Overall Survival
R. Cheung, S. Tucker, D. Kuban UT MD Anderson Cancer Center, Houston, TX Purpose/Objective: We analyzed whether first year PSA kinetics and nadirs are useful as early response indicators after prostate cancer radiotherapy (RT) in predicting overall survival (OS). Materials/Methods: The dataset included 1174 patients treated with external beam RT from 1987 to 2001. There were at least two PSA measurements during the first year after RT. The median patient age was 69 (Range 37 to 84). The median 1992 AJCC stage was T2a (range T1b to T4). The median Gleason score was 6 (range 2 to 10). The median pretreatment PSA was 7.8 (range 0.3 to 150). 298 patients had low-risk disease (PSA ⱕ 10 and Gleason score ⱕ 6 and AJCC stage T2a or lower disease), 472 had intermediate-risk disease, and 404 patients had high-risk disease (PSA ⬎ 20 or Gleason score ⱖ 8 or AJCC stage T3 or higher). Patients received a median dose of 70 Gy (range 60 to 78.2 Gy). Since we analyzed overall survival in this elderly patient population, we also included patient age in the analyses. For each patient, the relative rate of change () in post-treatment PSA values during the year (13.5 months) after RT was computed using regression analysis of ln( PSA) versus time. We also computed the PSA nadir (mPSA) reached during the first 13.5 month after RT. Univariate recursive partitioning analysis (RPA) was used to identify one or more relevant cutpoints for each of the continuous factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year nadir. For each of the other factors (stage, Gleason score, and risk group), all possible cutpoints were considered in the multivariate analyses (e.g. stage ⬍ T2a vs ⱖ T2a, stage ⬍ T2b vs ⱖ T2b, etc.). Cox proportional hazards analyses was used to identify independent predictors for overall survival. These predictors were then used to construct predictive models for OS. Results: The median value of was ⫺1.0 yr-1 (range ⫺11.0 to 5.1 yr-1). The 1-year nadir had a median of 0.8 ng/ml (range 0.01 to 30.9 ng/ml). The 5-year post-RT OS is 92% (95% CI 91% to 94%) and the 10-year OS is 69% (95% CI 66% to 73%). Univariate RPA identified the cutpoints for each of the continuous factors listed in Table 1.Cox proportional hazards analyses using both forward and backward stepwise selection of factors identified the same list of 8 factors adversely related to survival, with Hazard ratios (95% C.I.) and P-values: 1. Age ⱖ 71;1.61 (1.24, 2.09); ⬍ 0.001. 2. Age ⱖ 75;1.71 (1.26, 2.34);0.001. 3.Gleason score ⱖ 6;1.93 (1.48, 2.51); ⬍0.001. 4. Gleason score ⱖ 8;1.40 (1.02, 1.91);0.036. 5. Stage ⱖ T2b;1.29 (1.03, 1.61);0.024. 6.Dose ⬍ 66 Gy;1.37 (1.07, 1.77);0.013. 7. ⬎ 0 yr-1;1.68 (1.22, 2.32);0.002. 8.mPSA ⱖ 4 ng/ml;2.50 (1.70, 3.67);⬍0.001. The number of adverse factors was predictive of the overall survival. Patients with ⬎ 0 and/or mPSA ⱖ4 ng/ml during the first year post-RT had significantly worse survival for each of the groupings with ⱕ 2, 3, or ⱖ4 adverse factors vs. otherwise. Conclusions: First year post-RT PSA kinetics and nadirs, but not the pretreatment PSA, are predictive of overall survival for prostate cancer patients treated with RT. 1-year PSA kinetics and nadir may provide early RT response indicators to further segregate patients with other poor pretreatment prognostic factors into groups with better vs. worst overall survival. This information may be useful in selecting patients for adjuvant therapy after RT.
S199
S200
I. J. Radiation Oncology
● Biology ● Physics
Volume 63, Number 2, Supplement, 2005
Table 1
1092
The Percentage of Positive Cores Is Not an Appropriate Risk Factor for Prostate Radiotherapy to >72 Gy
M.K. Buyyounouski, A.L. Hanlon, E.M. Horwitz, A. Pollack Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective: There are few reports that study the utility of the percentage of positive cores (PPC) for predicting outcome following radiotherapy (RT) for prostate cancer and the results are mixed. The PPC is a rough approximation of tumor volume that is subject to considerable inaccuracy when: 1) the regions of the prostate are sampled disproportionately (i.e. the number of cores per region is not equal), 2) there are non-systematic biopsies directed towards suspicious areas that over represent positive regions, and 3) the cores are pooled during specimen collection which results in the loss of regional information. Furthermore, the PPC is not directly comparable in a population with varying degrees of sampling (i.e. total number of cores and/or regions). The far majority of reports that recommend using the PPC for guiding treatment are inadequate because they include extended time periods (e.g. 1988 to 2002) and conventional doses (e.g. 70 Gy). Prostate biopsy techniques have changed over time and conventional doses are no longer used. This report compares the PPC to more sophisticated techniques of estimating tumor volume in order to determine the best predictor of outcome in a contemporary series of high dose RT. Materials/Methods: From 1989 to 2001, 568 men with at least four biopsy cores treated with 3D conformal RT alone for T1c-3NX/0M0 (2002 AJCC) prostate cancer were retrospectively reviewed. Before 1997, it was determined that there were significantly fewer cores (p⬍.0001) and regions (p⬍.0001) sampled despite requiring a minimum of four cores. Thus, patients treated before 1997 were excluded to ensure similar prostate sampling among the entire group. Three hundred fourteen men with a median follow-up of 40 months (range: 13–77) and RT dose (ICRU) of 76 Gy (72– 82) were analyzed. The median number of cores was 7 (4 –24) with 94% having ⱖ6. The median number of biopsy regions sampled was 6 (1–12) where a region was defined as the label used to accession the biopsy (e.g. left apex or all pooled). The median patient age was 68 yrs (45– 83) and pretreatment PSA was 7 ng/mL (1.0 – 40.1). The proportion of men with T1c/2 was 97%, pretreatment PSA ⬍ 20 ng/mL was 94%, Gleason 7 was 24% and Gleason 8 –10 was 4%. The PPC was defined as the number of positive cores divided by the total number of cores. The percentage of positive regions (PPR) was defined as the number of regions positive divided by the total number of regions. The percentage of positive tissue (PPT) was calculated as the percentage of positive core length averaged over the number of cores per region then, averaged over the total number of regions. Cox univariate and multivariate analyses were used to determine the predictive value of each biopsy variable for biochemical failure (BF, ASTRO definition). Results: The median PPC was 25% (4 –100), PPR was 33% (10 –100) and PPT was 8% (⬍1– 68%). The proportion of men with PPC ⬎50% was 10%, PPR ⬎50% was 17% and PPT ⬎50% was ⬍1%. Univariate analysis for BF was significant for increasing PPT (p⫽.0136) but, not the PPC (p⫽.4480) or PPR (p⫽.3572). Independent predictors of higher BF among Gleason score (2– 6 vs 7 vs 8 –10), T-stage (T1/2 vs T3/4), pretreatment PSA, PPC, PPR, and dose (all continuous) were increasing PPT (p⫽.013) and Gleason score 8 –10 (p⫽.0433). Actuarial 5-yr BF (crude) for PPT ⱕ25% vs ⬎25% was 89% (25/280) vs 79% (7/34), p⫽.0255. Conclusions: The PPC should not be used to make any decisions regarding the management of prostate cancer with high dose RT. The only appropriate estimate of tumor volume with modern biopsy techniques is the PPT using the maximal amount of information available from the prostate biopsy. Simply correcting for the number of positive regions using the PPR does not stratify risk of recurrence following RT.
1093
Dosimetric Quantifiers for Low Dose Rate Prostate Brachytherapy: V100 Is Superior to D90
M.A. Papagikos,1 A.F. deGuzman,1 P.J. Rossi,1 D.L. McCullough,2 P.E. Clark,2 W.R. Lee1 Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 2Urology, Wake Forest University School of Medicine, Winston-Salem, NC 1
Purpose/Objective: The purpose of the present report is to describe the relationship between two dosimetric quantifiers (V100 and D90) and freedom from biochemical recurrence (FFBR) in a cohort of men treated with low dose rate prostate brachytherapy (LDRPB). Materials/Methods: One hundred three men were treated with LDRPB between September 1997 and December 1999. All men had histologically confirmed clinically localized prostate cancer. Sixty percent of the cohort had low-risk disease (defined as T stage ⬍ T2b and PSA ⬍ 10 and Gleason ⬍ 7) and 40% had intermediate-risk disease (defined as T stage T2b or PSA ⱖ 10
radiation dose to still be independent predictors of bF. However, RT technique was no longer significant. With either definition, on both univariate and multivariate analysis, radiation dose remained an independent predictor of biochemical failure. Conclusions: With changing definitions of bF, the results of failure analyses will change. In this large study sample with long median follow-up, the ASTRO definition resulted in worse bRFS rates earlier in the follow-up period (within the first 6 –7 years), while the nadir⫹2 definition resulted in worse outcomes later in the follow-up period (beyond 7– 8 years). Discrepancies in the results of the multivariate analyses were seen, such as radiation technique being significant in predicting bF with one definition (ASTRO), but not the other. Radiation dose, iPSA, bGS, and T stage remained important predictors of bF with either definition. On the basis of this analysis, no significant changes in the use of prognostic factors or treatment factors would be recommended.
Fig. 1
1091
First Year PSA Kinetics and Nadirs After Prostate Cancer Radiotherapy Are Predictive of Overall Survival
R. Cheung, S. Tucker, D. Kuban UT MD Anderson Cancer Center, Houston, TX Purpose/Objective: We analyzed whether first year PSA kinetics and nadirs are useful as early response indicators after prostate cancer radiotherapy (RT) in predicting overall survival (OS). Materials/Methods: The dataset included 1174 patients treated with external beam RT from 1987 to 2001. There were at least two PSA measurements during the first year after RT. The median patient age was 69 (Range 37 to 84). The median 1992 AJCC stage was T2a (range T1b to T4). The median Gleason score was 6 (range 2 to 10). The median pretreatment PSA was 7.8 (range 0.3 to 150). 298 patients had low-risk disease (PSA ⱕ 10 and Gleason score ⱕ 6 and AJCC stage T2a or lower disease), 472 had intermediate-risk disease, and 404 patients had high-risk disease (PSA ⬎ 20 or Gleason score ⱖ 8 or AJCC stage T3 or higher). Patients received a median dose of 70 Gy (range 60 to 78.2 Gy). Since we analyzed overall survival in this elderly patient population, we also included patient age in the analyses. For each patient, the relative rate of change () in post-treatment PSA values during the year (13.5 months) after RT was computed using regression analysis of ln( PSA) versus time. We also computed the PSA nadir (mPSA) reached during the first 13.5 month after RT. Univariate recursive partitioning analysis (RPA) was used to identify one or more relevant cutpoints for each of the continuous factors being investigated for its association with survival: age, pretreatment PSA, radiation dose, relative rate of change in PSA post-RT, and 1-year nadir. For each of the other factors (stage, Gleason score, and risk group), all possible cutpoints were considered in the multivariate analyses (e.g. stage ⬍ T2a vs ⱖ T2a, stage ⬍ T2b vs ⱖ T2b, etc.). Cox proportional hazards analyses was used to identify independent predictors for overall survival. These predictors were then used to construct predictive models for OS. Results: The median value of was ⫺1.0 yr-1 (range ⫺11.0 to 5.1 yr-1). The 1-year nadir had a median of 0.8 ng/ml (range 0.01 to 30.9 ng/ml). The 5-year post-RT OS is 92% (95% CI 91% to 94%) and the 10-year OS is 69% (95% CI 66% to 73%). Univariate RPA identified the cutpoints for each of the continuous factors listed in Table 1.Cox proportional hazards analyses using both forward and backward stepwise selection of factors identified the same list of 8 factors adversely related to survival, with Hazard ratios (95% C.I.) and P-values: 1. Age ⱖ 71;1.61 (1.24, 2.09); ⬍ 0.001. 2. Age ⱖ 75;1.71 (1.26, 2.34);0.001. 3.Gleason score ⱖ 6;1.93 (1.48, 2.51); ⬍0.001. 4. Gleason score ⱖ 8;1.40 (1.02, 1.91);0.036. 5. Stage ⱖ T2b;1.29 (1.03, 1.61);0.024. 6.Dose ⬍ 66 Gy;1.37 (1.07, 1.77);0.013. 7. ⬎ 0 yr-1;1.68 (1.22, 2.32);0.002. 8.mPSA ⱖ 4 ng/ml;2.50 (1.70, 3.67);⬍0.001. The number of adverse factors was predictive of the overall survival. Patients with ⬎ 0 and/or mPSA ⱖ4 ng/ml during the first year post-RT had significantly worse survival for each of the groupings with ⱕ 2, 3, or ⱖ4 adverse factors vs. otherwise. Conclusions: First year post-RT PSA kinetics and nadirs, but not the pretreatment PSA, are predictive of overall survival for prostate cancer patients treated with RT. 1-year PSA kinetics and nadir may provide early RT response indicators to further segregate patients with other poor pretreatment prognostic factors into groups with better vs. worst overall survival. This information may be useful in selecting patients for adjuvant therapy after RT.
S199
S200
I. J. Radiation Oncology
● Biology ● Physics
Volume 63, Number 2, Supplement, 2005
Table 1
1092
The Percentage of Positive Cores Is Not an Appropriate Risk Factor for Prostate Radiotherapy to >72 Gy
M.K. Buyyounouski, A.L. Hanlon, E.M. Horwitz, A. Pollack Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA Purpose/Objective: There are few reports that study the utility of the percentage of positive cores (PPC) for predicting outcome following radiotherapy (RT) for prostate cancer and the results are mixed. The PPC is a rough approximation of tumor volume that is subject to considerable inaccuracy when: 1) the regions of the prostate are sampled disproportionately (i.e. the number of cores per region is not equal), 2) there are non-systematic biopsies directed towards suspicious areas that over represent positive regions, and 3) the cores are pooled during specimen collection which results in the loss of regional information. Furthermore, the PPC is not directly comparable in a population with varying degrees of sampling (i.e. total number of cores and/or regions). The far majority of reports that recommend using the PPC for guiding treatment are inadequate because they include extended time periods (e.g. 1988 to 2002) and conventional doses (e.g. 70 Gy). Prostate biopsy techniques have changed over time and conventional doses are no longer used. This report compares the PPC to more sophisticated techniques of estimating tumor volume in order to determine the best predictor of outcome in a contemporary series of high dose RT. Materials/Methods: From 1989 to 2001, 568 men with at least four biopsy cores treated with 3D conformal RT alone for T1c-3NX/0M0 (2002 AJCC) prostate cancer were retrospectively reviewed. Before 1997, it was determined that there were significantly fewer cores (p⬍.0001) and regions (p⬍.0001) sampled despite requiring a minimum of four cores. Thus, patients treated before 1997 were excluded to ensure similar prostate sampling among the entire group. Three hundred fourteen men with a median follow-up of 40 months (range: 13–77) and RT dose (ICRU) of 76 Gy (72– 82) were analyzed. The median number of cores was 7 (4 –24) with 94% having ⱖ6. The median number of biopsy regions sampled was 6 (1–12) where a region was defined as the label used to accession the biopsy (e.g. left apex or all pooled). The median patient age was 68 yrs (45– 83) and pretreatment PSA was 7 ng/mL (1.0 – 40.1). The proportion of men with T1c/2 was 97%, pretreatment PSA ⬍ 20 ng/mL was 94%, Gleason 7 was 24% and Gleason 8 –10 was 4%. The PPC was defined as the number of positive cores divided by the total number of cores. The percentage of positive regions (PPR) was defined as the number of regions positive divided by the total number of regions. The percentage of positive tissue (PPT) was calculated as the percentage of positive core length averaged over the number of cores per region then, averaged over the total number of regions. Cox univariate and multivariate analyses were used to determine the predictive value of each biopsy variable for biochemical failure (BF, ASTRO definition). Results: The median PPC was 25% (4 –100), PPR was 33% (10 –100) and PPT was 8% (⬍1– 68%). The proportion of men with PPC ⬎50% was 10%, PPR ⬎50% was 17% and PPT ⬎50% was ⬍1%. Univariate analysis for BF was significant for increasing PPT (p⫽.0136) but, not the PPC (p⫽.4480) or PPR (p⫽.3572). Independent predictors of higher BF among Gleason score (2– 6 vs 7 vs 8 –10), T-stage (T1/2 vs T3/4), pretreatment PSA, PPC, PPR, and dose (all continuous) were increasing PPT (p⫽.013) and Gleason score 8 –10 (p⫽.0433). Actuarial 5-yr BF (crude) for PPT ⱕ25% vs ⬎25% was 89% (25/280) vs 79% (7/34), p⫽.0255. Conclusions: The PPC should not be used to make any decisions regarding the management of prostate cancer with high dose RT. The only appropriate estimate of tumor volume with modern biopsy techniques is the PPT using the maximal amount of information available from the prostate biopsy. Simply correcting for the number of positive regions using the PPR does not stratify risk of recurrence following RT.
1093
Dosimetric Quantifiers for Low Dose Rate Prostate Brachytherapy: V100 Is Superior to D90
M.A. Papagikos,1 A.F. deGuzman,1 P.J. Rossi,1 D.L. McCullough,2 P.E. Clark,2 W.R. Lee1 Radiation Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, 2Urology, Wake Forest University School of Medicine, Winston-Salem, NC 1
Purpose/Objective: The purpose of the present report is to describe the relationship between two dosimetric quantifiers (V100 and D90) and freedom from biochemical recurrence (FFBR) in a cohort of men treated with low dose rate prostate brachytherapy (LDRPB). Materials/Methods: One hundred three men were treated with LDRPB between September 1997 and December 1999. All men had histologically confirmed clinically localized prostate cancer. Sixty percent of the cohort had low-risk disease (defined as T stage ⬍ T2b and PSA ⬍ 10 and Gleason ⬍ 7) and 40% had intermediate-risk disease (defined as T stage T2b or PSA ⱖ 10