Daniel A Hamstra1, Stephanie L Pugh2, Herbert Lepor3, Seth A Rosenthal4, Kenneth J Pienta5, Leonard Gomella6, Christopher Peters7, David Paul D'Souza8, Kenneth L Zeitzer9, Christopher U Jones10, William A Hall11, Eric Horwitz12, Thomas M Pisansky13, Luis Souhami14, Alan C Hartford15, Michael Dominello16, Felix Feng17, Howard M Sandler18. 1. William Beaumont Oakland University Medical School, The Department of Radiation Oncology, Beaumont Health - Dearborn, USA. Electronic address: Daniel.Hamstra@beaumont.org. 2. NRG Oncology Statistics and Data Management Center, Philadelphia, USA. Electronic address: PughS@NRGOncology.org. 3. New York University, USA. Electronic address: herbert.lepor@med.nyu.edu. 4. Sutter General Hospital, Radiation Oncology Center, Roseville, USA; Radiation Oncology Center, Sacramenta, USA. Electronic address: rosents@sutterhealth.org. 5. Johns Hopkins University/Sidney Kimmel Cancer Center, Baltimore, USA. Electronic address: kpienta1@jhmi.edu. 6. Thomas Jefferson University Hospital, Philadelphia, USA. Electronic address: leonard.gomella@jefferson.edu. 7. Northeast Radiation Oncology Center, Dunmore, USA. Electronic address: chris.peters@hmrnet.com. 8. London Regional Cancer Program, London Health Sciences Centre, Canada. Electronic address: david.dsouza@lhsc.on.ca. 9. Albert Einstein Medical Center, Department of Radiation Oncology, Philadelphia, USA. Electronic address: zeitzerk@einstein.edu. 10. Sutter General Hospital, Radiation Oncology Center, Roseville, USA; Radiation Oncology Center, Sacramenta, USA. 11. Zablocki VA Medical Center-Wood, Milwaukee, USA. Electronic address: whall@mcw.edu. 12. Fox Chase Cancer Center, Philadelphia, USA. Electronic address: eric.horwitz@fccc.edu. 13. Mayo Clinic, Rochester, USA. Electronic address: pisansky.thomas@mayo.edu. 14. McGill University, Cedars Cancer Centre Glen Site, Montreal, USA. Electronic address: luis.souhami@mcgill.ca. 15. Dartmouth-Hitchcock Medical Center/Norris Cotton Cancer Center, Radiation Oncology, Lebanon, USA. Electronic address: alan.c.hartford@dartmouth.edu. 16. Wayne State University/Karmanos Cancer Institute, Gershenson Radiation Oncology Center, Detroit, USA. Electronic address: mdominel@med.wayne.edu. 17. University of California San Francisco, USA. Electronic address: felix.feng@ucsf.edu. 18. Cedars-Sinai Medical Center, Department of Radiation Oncology, Los Angeles, USA. Electronic address: howard.sandler@cshs.org.
Abstract
BACKGROUND/ PURPOSE: Stratification of Gleason score (GS) into three categories (2-6, 7, and 8-10) may not fully utilize its prognostic discrimination, with Gleason pattern 5 (GP5) previously identified as an independent adverse factor. MATERIALS/ METHODS: Patients treated on RTOG 9202 (n = 1292) or RTOG 9902 (n = 378) were pooled and assessed for association of GS and GP5 on biochemical failure (BF), local failure (LF), distant metastasis (DM), and overall survival (OS). Fine and Gray's regression and cumulative incidence methods were used for univariate and multivariate analyses. RESULTS: With median follow-up of 9.4 years, patients with GS 8-10 with GP5 had worse outcome than GS 4 + 4 for DM on both RTOG9202 (p = 0.038) and RTOG9902 (p < 0.001) with a trend toward worse OS (p = 0.059 and p = 0.089, respectively), but without differences in BF or LF. At 10-years DM was higher by 11% (RTOG 9202) and 18% (RTOG 9902) with GP5 compared to GS 4 + 4. On multivariate analysis restricted to long-term androgen deprivation therapy the presence of GP5 substantially increased distant metastasis (HR = 0.43, 95%CI: 0.24-0.76, p = 0.0039) with a trend toward worse OS (HR:0.74, 95% CI:0.54-1.0, p = 0.052) without association with LF (HR:0.55, 95%CI:0.28-1.09, p = 0.085) or BF (HR:1.15, 95%CI:0.84-1.59, p = 0.39). We did not observed substantial differences between Gleason 3 + 5, 5 + 3, or Gleason 9-10. CONCLUSIONS: These results validate GP5 as an independent prognostic factor which is strongest for DM. As a result GP5 should be considered when stratifying patients with GS 8 and may be a patient population in which to evaluate newly approved systemic therapies or additional local treatments.
BACKGROUND/ PURPOSE: Stratification of Gleason score (GS) into three categories (2-6, 7, and 8-10) may not fully utilize its prognostic discrimination, with Gleason pattern 5 (GP5) previously identified as an independent adverse factor. MATERIALS/ METHODS:Patients treated on RTOG 9202 (n = 1292) or RTOG 9902 (n = 378) were pooled and assessed for association of GS and GP5 on biochemical failure (BF), local failure (LF), distant metastasis (DM), and overall survival (OS). Fine and Gray's regression and cumulative incidence methods were used for univariate and multivariate analyses. RESULTS: With median follow-up of 9.4 years, patients with GS 8-10 with GP5 had worse outcome than GS 4 + 4 for DM on both RTOG9202 (p = 0.038) and RTOG9902 (p < 0.001) with a trend toward worse OS (p = 0.059 and p = 0.089, respectively), but without differences in BF or LF. At 10-years DM was higher by 11% (RTOG 9202) and 18% (RTOG 9902) with GP5 compared to GS 4 + 4. On multivariate analysis restricted to long-term androgen deprivation therapy the presence of GP5 substantially increased distant metastasis (HR = 0.43, 95%CI: 0.24-0.76, p = 0.0039) with a trend toward worse OS (HR:0.74, 95% CI:0.54-1.0, p = 0.052) without association with LF (HR:0.55, 95%CI:0.28-1.09, p = 0.085) or BF (HR:1.15, 95%CI:0.84-1.59, p = 0.39). We did not observed substantial differences between Gleason 3 + 5, 5 + 3, or Gleason 9-10. CONCLUSIONS: These results validate GP5 as an independent prognostic factor which is strongest for DM. As a result GP5 should be considered when stratifying patients with GS 8 and may be a patient population in which to evaluate newly approved systemic therapies or additional local treatments.
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