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The Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer
I. J. Radiation Oncology d Biology d Physics
S554
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Volume 81, Number 2, Supplement, 2011
The Role of Surgical Resection Following Primary Chemoradiation Therapy in Esophageal Squamous Cell Carcinoma: A Decision Analysis
A. Goenka, E. Elkin, L. Shapiro, N. P. Rizk, D. H. Ilson, M. S. Bains, V. Rusch, K. A. Goodman Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): The role of definitive surgical resection following a complete clinical and radiographic response to chemoradiation therapy (CRT) for esophageal squamous cell carcinoma (SCC) is controversial. We used decision analysis to estimate overall and quality adjusted life expectancy associated with competing strategies for managing these patients. Materials/Methods: We developed a Markov state transition model to simulate the natural history of esophageal SCC following chemoradiation therapy. The model was defined for a hypothetical 60-year old male with a complete metabolic response posttreatment by positron emission tomography (PET). We compared two strategies: immediate surgery in all patients (SURG) vs. observation (OBS) in patients who have no evidence of disease following endoscopic ultrasound and biopsies (EUS-Bx). In the base case we assumed that PET sensitivity and specificity were both 67%, and EUS-Bx had a sensitivity of 40%. We did not consider surgical salvage as an option for patients who experienced local failure. Primary outcomes were life years and quality-adjusted life years (QALYs). Transition probabilities and health-state utilities were obtained from the literature and from expert option. Sensitivity analysis was performed to assess the robustness of results to model assumptions. Results: In the base case, mean life expectancy was 3.53 years for the SURG strategy and 3.57 years for the OBS strategy. Mean quality-adjusted life expectancy was 2.27 years for the SURG strategy and 2.35 yrs for the OBS strategy, a gain of 0.08 QALYs, or about 1 month of quality-adjusted survival. In the OBS strategy, the probability of having residual disease and continued observation, despite a negative PET and EUS-bx, was 20%. In one-way sensitivity analysis, the OBS strategy was favored if the probability of a pathologic complete response was $ 35% and if surgical mortality was $ 2.8%. Results were not sensitive to assumptions about the rate of local recurrence, the risk of death following local recurrence, or quality of life following local recurrence. Over a wide range of plausible values for PET sensitivity and specificity the OBS strategy was favored. Conclusions: Our results suggest that among a well selected group of esophageal SCC patients who obtain a complete response on PET and a negative EUS-bx following chemoradiation therapy, immediate surgical resection may not improve mean life expectancy or QALY’s compared with chemoradiation alone. In the absence of a large randomized trial, this decision-analytic simulation supports observation as an appropriate treatment strategy for select patients who have a complete response by PET. Author Disclosure: A. Goenka: None. E. Elkin: None. L. Shapiro: None. N.P. Rizk: None. D.H. Ilson: None. M.S. Bains: None. V. Rusch: None. K.A. Goodman: None.
2717
The Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer
J. Kang1, M. Chen2, Y. Zhang3, B. J. Moran4, D. E. Dosoretz4, M. J. Katin4, M. H. Braccioforte3, S. A. Salenius4, A. V. D’Amico1 1 Harvard Radiation Oncology Program, Boston, MA, 2Department of Statistics, University of Connecticut, Storrs, CT, 3Prostate Cancer Foundation of Chicago, Chicago, IL, 4Department of Radiation Oncology, 21 Century Oncology, Inc., Fort Myers, FL
Purpose/Objective(s): In addition to increasing age and PSA level, family history and African-American (AA) race, it has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 - 10 ; however whether this association holds for both type I and II DM is unknown. In this study we evaluated whether DM type I, II or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. Materials/Methods: Between 1991 and 2010, 15,330 men, newly diagnosed with PCa and treated with radiation therapy at 1 of 26 centers, were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether a diagnosis of type I or II DM was associated with the odds of GS 7 or 8 to 10 compared to 6 or less PCa, adjusting for AA race, age, PSA level, and digital rectal examination (DRE) findings. Results: As shown in the table, men with type I DM (Adjusted Odds Ratio (AOR), 2.05; 95% Confidence Interval (CI), 1.28 3.27; P = 0.003) or type II DM (AOR, 1.58; 95% CI, 1.26 - 1.99; P\0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared to non-diabetics. However this was not true for GS 7 where these respective results were AOR, 1.30; 95% CI, 0.93 - 1.82; P = 0.12 and AOR, 1.13; 95% CI, 0.98 - 1.32; P = 0.10. Conclusions: Type I and II DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, similar to African American men, consideration of early prostate cancer screening could be given to men with DM particularly those with type I DM whose onset is typically during adolescence.
Odds Ratio of GS7 vs GS6 or lower, or GS8 - 10 vs GS6 or lower at time of diagnosis Clinical Factor
Gleason score
AOR [95% CI]
p-value
DM I DM I DM II DM II AA race AA race PSA, Age, Abnormal DRE PSA, Age, Abnormal DRE
7 8 to 10 7 8 to 10 7 8 to 10 7 8 to 10
1.30 [0.93 - 1.82] 2.05 [1.28 - 3.27] 1.13 [0.98 - 1.32] 1.58 [1.26 - 1.99] 1.47 [1.26 - 1.72] 1.45 [1.10 - 1.92] 1.50 [1.42 - 1.60], 1.02 [1.02 - 1.03], 2.24 [2.08 - 2.42] 1.98 [1.80 - 2.19], 1.06 [1.05 - 1.07], 3.12 [2.74 - 3.55]
0.12 0.003 0.10 \0.001 \0.001 0.008 \0.001, \0.001, \0.001 \0.001,\0.001,\0.001
Author Disclosure: J. Kang: None. M. Chen: None. Y. Zhang: None. B.J. Moran: None. D.E. Dosoretz: None. M.J. Katin: None. M.H. Braccioforte: None. S.A. Salenius: None. A.V. D’Amico: None.
S554
2716
Volume 81, Number 2, Supplement, 2011
The Role of Surgical Resection Following Primary Chemoradiation Therapy in Esophageal Squamous Cell Carcinoma: A Decision Analysis
A. Goenka, E. Elkin, L. Shapiro, N. P. Rizk, D. H. Ilson, M. S. Bains, V. Rusch, K. A. Goodman Memorial Sloan Kettering Cancer Center, New York, NY Purpose/Objective(s): The role of definitive surgical resection following a complete clinical and radiographic response to chemoradiation therapy (CRT) for esophageal squamous cell carcinoma (SCC) is controversial. We used decision analysis to estimate overall and quality adjusted life expectancy associated with competing strategies for managing these patients. Materials/Methods: We developed a Markov state transition model to simulate the natural history of esophageal SCC following chemoradiation therapy. The model was defined for a hypothetical 60-year old male with a complete metabolic response posttreatment by positron emission tomography (PET). We compared two strategies: immediate surgery in all patients (SURG) vs. observation (OBS) in patients who have no evidence of disease following endoscopic ultrasound and biopsies (EUS-Bx). In the base case we assumed that PET sensitivity and specificity were both 67%, and EUS-Bx had a sensitivity of 40%. We did not consider surgical salvage as an option for patients who experienced local failure. Primary outcomes were life years and quality-adjusted life years (QALYs). Transition probabilities and health-state utilities were obtained from the literature and from expert option. Sensitivity analysis was performed to assess the robustness of results to model assumptions. Results: In the base case, mean life expectancy was 3.53 years for the SURG strategy and 3.57 years for the OBS strategy. Mean quality-adjusted life expectancy was 2.27 years for the SURG strategy and 2.35 yrs for the OBS strategy, a gain of 0.08 QALYs, or about 1 month of quality-adjusted survival. In the OBS strategy, the probability of having residual disease and continued observation, despite a negative PET and EUS-bx, was 20%. In one-way sensitivity analysis, the OBS strategy was favored if the probability of a pathologic complete response was $ 35% and if surgical mortality was $ 2.8%. Results were not sensitive to assumptions about the rate of local recurrence, the risk of death following local recurrence, or quality of life following local recurrence. Over a wide range of plausible values for PET sensitivity and specificity the OBS strategy was favored. Conclusions: Our results suggest that among a well selected group of esophageal SCC patients who obtain a complete response on PET and a negative EUS-bx following chemoradiation therapy, immediate surgical resection may not improve mean life expectancy or QALY’s compared with chemoradiation alone. In the absence of a large randomized trial, this decision-analytic simulation supports observation as an appropriate treatment strategy for select patients who have a complete response by PET. Author Disclosure: A. Goenka: None. E. Elkin: None. L. Shapiro: None. N.P. Rizk: None. D.H. Ilson: None. M.S. Bains: None. V. Rusch: None. K.A. Goodman: None.
2717
The Type of Diabetes Mellitus and the Odds of Gleason Score 8 to 10 Prostate Cancer
J. Kang1, M. Chen2, Y. Zhang3, B. J. Moran4, D. E. Dosoretz4, M. J. Katin4, M. H. Braccioforte3, S. A. Salenius4, A. V. D’Amico1 1 Harvard Radiation Oncology Program, Boston, MA, 2Department of Statistics, University of Connecticut, Storrs, CT, 3Prostate Cancer Foundation of Chicago, Chicago, IL, 4Department of Radiation Oncology, 21 Century Oncology, Inc., Fort Myers, FL
Purpose/Objective(s): In addition to increasing age and PSA level, family history and African-American (AA) race, it has been recently shown that diabetes mellitus (DM) is significantly associated with the likelihood of presenting with high-grade prostate cancer (PCa) or Gleason score (GS) 8 - 10 ; however whether this association holds for both type I and II DM is unknown. In this study we evaluated whether DM type I, II or both are associated with high-grade PCa after adjusting for known predictors of high-grade disease. Materials/Methods: Between 1991 and 2010, 15,330 men, newly diagnosed with PCa and treated with radiation therapy at 1 of 26 centers, were analyzed. A polychotomous logistic regression analysis was performed to evaluate whether a diagnosis of type I or II DM was associated with the odds of GS 7 or 8 to 10 compared to 6 or less PCa, adjusting for AA race, age, PSA level, and digital rectal examination (DRE) findings. Results: As shown in the table, men with type I DM (Adjusted Odds Ratio (AOR), 2.05; 95% Confidence Interval (CI), 1.28 3.27; P = 0.003) or type II DM (AOR, 1.58; 95% CI, 1.26 - 1.99; P\0.001) were significantly more likely to be diagnosed with GS 8 to 10 PCa compared to non-diabetics. However this was not true for GS 7 where these respective results were AOR, 1.30; 95% CI, 0.93 - 1.82; P = 0.12 and AOR, 1.13; 95% CI, 0.98 - 1.32; P = 0.10. Conclusions: Type I and II DM were associated with a higher odds of being diagnosed with Gleason score 8 to 10 but not 7 PCa. Pending validation, similar to African American men, consideration of early prostate cancer screening could be given to men with DM particularly those with type I DM whose onset is typically during adolescence.
Odds Ratio of GS7 vs GS6 or lower, or GS8 - 10 vs GS6 or lower at time of diagnosis Clinical Factor
Gleason score
AOR [95% CI]
p-value
DM I DM I DM II DM II AA race AA race PSA, Age, Abnormal DRE PSA, Age, Abnormal DRE
7 8 to 10 7 8 to 10 7 8 to 10 7 8 to 10
1.30 [0.93 - 1.82] 2.05 [1.28 - 3.27] 1.13 [0.98 - 1.32] 1.58 [1.26 - 1.99] 1.47 [1.26 - 1.72] 1.45 [1.10 - 1.92] 1.50 [1.42 - 1.60], 1.02 [1.02 - 1.03], 2.24 [2.08 - 2.42] 1.98 [1.80 - 2.19], 1.06 [1.05 - 1.07], 3.12 [2.74 - 3.55]
0.12 0.003 0.10 \0.001 \0.001 0.008 \0.001, \0.001, \0.001 \0.001,\0.001,\0.001
Author Disclosure: J. Kang: None. M. Chen: None. Y. Zhang: None. B.J. Moran: None. D.E. Dosoretz: None. M.J. Katin: None. M.H. Braccioforte: None. S.A. Salenius: None. A.V. D’Amico: None.