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2223
S334
I. J. Radiation Oncology
2223
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
The Effect of Treatment on Development of Second Primary Cancer in Prostate Cancer Patients: An Analysis of SEER Data
M. Abdel-Wahab1, I. M. Reis2, J. Wu3 1 Department of Radiation Oncology, University of Miami, Miami, FL, 2University of Miami, Department of Epidemiology and Public Health, Miami, FL, 3Biostatistics, RTP- PPD inc, Morrisville, NC Purpose/Objective(s): To assess the effect of treatment for prostate cancer on development of second primary cancer (SPC). Materials/Methods: The analysis included 148,444 prostate cancer patients in the 1973–2002 SEER database, who were diagnosed between 1988 –2000 with a single prostate primary or prostate cancer as the first of two or more malignancies. These patients had local/regional adenocarcinoma,. Exclusions included cases diagnosed by autopsy or death certificate, cases with survival or follow-up of less than one year, and those where SPC diagnosis was within 1 year of primary prostate cancer. Results: The incidence of SPC was 9% (13,345 cases), with 2.4% (3,559 cases) in pelvic areas and 6.6% (9,786 cases) in non-pelvic areas. In the pelvic area, the most frequent sites of SPC were bladder (1,633 cases), hematopoietic (914 cases), rectum/ rectosigmoid junction (1,148 cases). In non-pelvic areas, the most frequent sites of SPC were bronchus and lung (2,656 cases), colon (1,890 cases), and skin (1,201cases). Radiation was associated with a higher risk of occurrence of SPC in pelvic area (odds ratio 1.13, 95%CI: 1.04 –1.22). For those who received radiation treatment, the 5-year and 10-year SPC-free rates were 92.5% and 82.2%, while for those patients who did not the corresponding rates were 94.2% and 86.9%. Cox multivariate analysis showed that radiation, type of surgery, age and race/ethnicity are important predictors of SPC-free survival. Men 60 –79 years of age and ⱖ80 years old were at a 2.15 (95%CI: 2.01–2.31) and 2.55 (95%CI: 2.33 -2.79) higher risk of developing SPC than men less than 60 years old. Blacks had a similar risk as white non-Hispanics (HR 1.02, 95%CI: 0.96 –1.08), but white Hispanics (HR 0.72, 95%CI: 0.65– 0.81) and “other” (HR 0.79, 95%CI: 0.72– 0.86) had lower risk of SPC than white non-Hispanics. With regard to treatment, patients treated with a combination of radiation and radical surgery had significant decrease in SPC, with a HR of 0.78, (95% CI: 0.69 – 0.88) as compared to the reference group ‘no radiation and no surgery’. Patients treated with a combination of radiation and non-radical surgery had an increased risk of SPC, with a HR of 1.09 (95% CI: 1.01–1.17) as compared to the reference group ‘no radiation and no surgery’. Patients treated with radiation only had an increased risk of SPC (HR 1.08, 95%CI: 1.02 to 1.14), while radical surgery only decreased the risk of SPC (HR 0.72, 95%CI: 0.68 – 0.76). The hazard ratio associated with non-radical surgery only compared to ‘no radiation and no surgery’ was 0.92 (95%CI: 0.87– 0.98). Conclusions: Prostate cancer treatment with radiation alone or with non-radical surgery led to an increase in SPC risk as compared to untreated patients. However, radiation given after radical surgery was not associated with an increase in risk of SPC. Author Disclosure: M. Abdel-Wahab, None; I.M. Reis, None; J. Wu, None.
2224
Prostate Specific Antigen Kinetics in Men Treated With Radiotherapy and Androgen Deprivation
D. J. D’Ambrosio, K. Ruth, M. K. Buyyounouski, E. M. Horwitz, R. G. Uzzo, A. Pollack Fox Chase Cancer Center, Philadelphia, PA Background: The prostate specific antigen (PSA) level usually rises following radiotherapy (RT) and androgen deprivation therapy (ADT), complicating the evaluation of biochemical outcome. The PSA nadir ⫹2 ng/mL definition of biochemical failure (BF) has been shown to reduce misclassifications, and more accurately predict future rises in PSA and eventual clinical outcome. However, the classification of BF following RT⫹ADT for high risk disease may be delayed because PSA nadir levels are usually undetectable. Purpose/Objective(s): The purpose of this study was to test post-ADT PSA level characteristics as an early predictor for nadir ⫹ 2 BF in men with high risk prostate cancer. Materials/Methods: From 7/92 to 3/04, 367 men with high risk prostate cancer (clinical stage T3 or Gleason score (GS) 8 –10 or pretreatment PSA ⬎20 ng/mL) were treated with definitive RT and ADT (median dose: 76Gy). Seventy eight percent (n⫽286) received 3D conformal RT and 22% (n⫽81) received intensity-modulated radiotherapy. The proportion of men that received ⬍12 months of ADT was 58%. An undetectable PSA was defined as ⱕ0.2 ng/mL. Various post-nadir PSA variables were studied including an absolute increase in PSA of at least 0.5, 1.0, and 1.5 ng/mL following the release of ADT. The PSA velocity was also studied and was calculated as the difference in PSA between two time points divided by the time in months. The Cox proportional hazards model was used for univariate and multivariate analyses for nadir⫹2 BF. Results: The median follow-up was 65 months. The median pretreatment PSA was 12.7 ng/mL and the median GS was 7. The median number of PSAs was 8 and the median interval between PSAs was 6 months. The median first post nadir PSA was 0.3 ng/ml (range:0.2–3.5). Eighty one men (22%) experienced BF. The median time to BF was 39 months (range:3–145) and the median increase in PSA at failure was 1.5 (range:0.2–10.1). The proportion of men with a rise in PSA of ⱖ0.5ng/mL following the release of ADT was 12%. The five year rate of BF was 48% for a post nadir PSA rise of ⱖ5ng/mL and 11% for a post nadir PSA rise of ⬍0.5ng/mL(p⬍0.0001). Independent predictors of BF in multivariate analysis were GS 7–10 (p⫽0.001), T3 (p⫽0.049), pretreatment PSA (p⫽0.001), RT dose (p⫽0.004), duration of AD ⬍12 months (p⫽0.011), PSA nadir (p⫽0.021), and a rise in PSA of ⱖ0.5ng/ml from the nadir (p⫽0.0003). Non significant covariates in the model were post-treatment PSA velocity, and absolute increases in PSA of 1 or 1.5ng/ml immediately following the nadir. Conclusions: Men who have been treated with RT⫹ADT have different PSA kinetics than what is observed following definitive RT alone. An increase in PSA of 0.5 ng/mL in the first post nadir PSA following the release of ADT is an independent predictor of future rises and eventual BF. Earlier detection affords a greater opportunity for successful salvage therapy. Author Disclosure: D.J. D’Ambrosio, None; K. Ruth, None; M.K. Buyyounouski, None; E.M. Horwitz, None; R.G. Uzzo, None; A. Pollack, Varian, B. Research Grant; Tap Pharmaceuticals, D. Speakers Bureau/Honoraria; Astrazeneca, D. Speakers Bureau/Honoraria.
I. J. Radiation Oncology
2223
● Biology ● Physics
Volume 66, Number 3, Supplement, 2006
The Effect of Treatment on Development of Second Primary Cancer in Prostate Cancer Patients: An Analysis of SEER Data
M. Abdel-Wahab1, I. M. Reis2, J. Wu3 1 Department of Radiation Oncology, University of Miami, Miami, FL, 2University of Miami, Department of Epidemiology and Public Health, Miami, FL, 3Biostatistics, RTP- PPD inc, Morrisville, NC Purpose/Objective(s): To assess the effect of treatment for prostate cancer on development of second primary cancer (SPC). Materials/Methods: The analysis included 148,444 prostate cancer patients in the 1973–2002 SEER database, who were diagnosed between 1988 –2000 with a single prostate primary or prostate cancer as the first of two or more malignancies. These patients had local/regional adenocarcinoma,. Exclusions included cases diagnosed by autopsy or death certificate, cases with survival or follow-up of less than one year, and those where SPC diagnosis was within 1 year of primary prostate cancer. Results: The incidence of SPC was 9% (13,345 cases), with 2.4% (3,559 cases) in pelvic areas and 6.6% (9,786 cases) in non-pelvic areas. In the pelvic area, the most frequent sites of SPC were bladder (1,633 cases), hematopoietic (914 cases), rectum/ rectosigmoid junction (1,148 cases). In non-pelvic areas, the most frequent sites of SPC were bronchus and lung (2,656 cases), colon (1,890 cases), and skin (1,201cases). Radiation was associated with a higher risk of occurrence of SPC in pelvic area (odds ratio 1.13, 95%CI: 1.04 –1.22). For those who received radiation treatment, the 5-year and 10-year SPC-free rates were 92.5% and 82.2%, while for those patients who did not the corresponding rates were 94.2% and 86.9%. Cox multivariate analysis showed that radiation, type of surgery, age and race/ethnicity are important predictors of SPC-free survival. Men 60 –79 years of age and ⱖ80 years old were at a 2.15 (95%CI: 2.01–2.31) and 2.55 (95%CI: 2.33 -2.79) higher risk of developing SPC than men less than 60 years old. Blacks had a similar risk as white non-Hispanics (HR 1.02, 95%CI: 0.96 –1.08), but white Hispanics (HR 0.72, 95%CI: 0.65– 0.81) and “other” (HR 0.79, 95%CI: 0.72– 0.86) had lower risk of SPC than white non-Hispanics. With regard to treatment, patients treated with a combination of radiation and radical surgery had significant decrease in SPC, with a HR of 0.78, (95% CI: 0.69 – 0.88) as compared to the reference group ‘no radiation and no surgery’. Patients treated with a combination of radiation and non-radical surgery had an increased risk of SPC, with a HR of 1.09 (95% CI: 1.01–1.17) as compared to the reference group ‘no radiation and no surgery’. Patients treated with radiation only had an increased risk of SPC (HR 1.08, 95%CI: 1.02 to 1.14), while radical surgery only decreased the risk of SPC (HR 0.72, 95%CI: 0.68 – 0.76). The hazard ratio associated with non-radical surgery only compared to ‘no radiation and no surgery’ was 0.92 (95%CI: 0.87– 0.98). Conclusions: Prostate cancer treatment with radiation alone or with non-radical surgery led to an increase in SPC risk as compared to untreated patients. However, radiation given after radical surgery was not associated with an increase in risk of SPC. Author Disclosure: M. Abdel-Wahab, None; I.M. Reis, None; J. Wu, None.
2224
Prostate Specific Antigen Kinetics in Men Treated With Radiotherapy and Androgen Deprivation
D. J. D’Ambrosio, K. Ruth, M. K. Buyyounouski, E. M. Horwitz, R. G. Uzzo, A. Pollack Fox Chase Cancer Center, Philadelphia, PA Background: The prostate specific antigen (PSA) level usually rises following radiotherapy (RT) and androgen deprivation therapy (ADT), complicating the evaluation of biochemical outcome. The PSA nadir ⫹2 ng/mL definition of biochemical failure (BF) has been shown to reduce misclassifications, and more accurately predict future rises in PSA and eventual clinical outcome. However, the classification of BF following RT⫹ADT for high risk disease may be delayed because PSA nadir levels are usually undetectable. Purpose/Objective(s): The purpose of this study was to test post-ADT PSA level characteristics as an early predictor for nadir ⫹ 2 BF in men with high risk prostate cancer. Materials/Methods: From 7/92 to 3/04, 367 men with high risk prostate cancer (clinical stage T3 or Gleason score (GS) 8 –10 or pretreatment PSA ⬎20 ng/mL) were treated with definitive RT and ADT (median dose: 76Gy). Seventy eight percent (n⫽286) received 3D conformal RT and 22% (n⫽81) received intensity-modulated radiotherapy. The proportion of men that received ⬍12 months of ADT was 58%. An undetectable PSA was defined as ⱕ0.2 ng/mL. Various post-nadir PSA variables were studied including an absolute increase in PSA of at least 0.5, 1.0, and 1.5 ng/mL following the release of ADT. The PSA velocity was also studied and was calculated as the difference in PSA between two time points divided by the time in months. The Cox proportional hazards model was used for univariate and multivariate analyses for nadir⫹2 BF. Results: The median follow-up was 65 months. The median pretreatment PSA was 12.7 ng/mL and the median GS was 7. The median number of PSAs was 8 and the median interval between PSAs was 6 months. The median first post nadir PSA was 0.3 ng/ml (range:0.2–3.5). Eighty one men (22%) experienced BF. The median time to BF was 39 months (range:3–145) and the median increase in PSA at failure was 1.5 (range:0.2–10.1). The proportion of men with a rise in PSA of ⱖ0.5ng/mL following the release of ADT was 12%. The five year rate of BF was 48% for a post nadir PSA rise of ⱖ5ng/mL and 11% for a post nadir PSA rise of ⬍0.5ng/mL(p⬍0.0001). Independent predictors of BF in multivariate analysis were GS 7–10 (p⫽0.001), T3 (p⫽0.049), pretreatment PSA (p⫽0.001), RT dose (p⫽0.004), duration of AD ⬍12 months (p⫽0.011), PSA nadir (p⫽0.021), and a rise in PSA of ⱖ0.5ng/ml from the nadir (p⫽0.0003). Non significant covariates in the model were post-treatment PSA velocity, and absolute increases in PSA of 1 or 1.5ng/ml immediately following the nadir. Conclusions: Men who have been treated with RT⫹ADT have different PSA kinetics than what is observed following definitive RT alone. An increase in PSA of 0.5 ng/mL in the first post nadir PSA following the release of ADT is an independent predictor of future rises and eventual BF. Earlier detection affords a greater opportunity for successful salvage therapy. Author Disclosure: D.J. D’Ambrosio, None; K. Ruth, None; M.K. Buyyounouski, None; E.M. Horwitz, None; R.G. Uzzo, None; A. Pollack, Varian, B. Research Grant; Tap Pharmaceuticals, D. Speakers Bureau/Honoraria; Astrazeneca, D. Speakers Bureau/Honoraria.