Keiichiro Mori1, Vidit Sharma2, Eva M Comperat3, Shun Sato4, Ekaterina Laukhtina5, Victor M Schuettfort6, Benjamin Pradere7, Mehdi Kardoust Parizi8, Pierre I Karakiewicz9, Shin Egawa10, Derya Tilki11, Stephen A Boorjian12, Shahrokh F Shariat13. 1. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 2. Department of Urology, Mayo Clinic, Rochester, MN, USA; VA Health Services Research and Development Fellowship, Department of Urology, University of California, Los Angeles, USA. 3. Department of Pathology, Hôpital Tenon, Sorbonne University, Paris, France. 4. Departments of Pathology, The Jikei University School of Medicine, Tokyo, Japan. 5. Department of Urology, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia. 6. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 7. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, University Hospital of Tours, Tours, France. 8. Department of Urology, Medical University of Vienna, Vienna, Austria; Department of Urology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran. 9. Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada. 10. Department of Urology, The Jikei University School of Medicine, Tokyo, Japan. 11. Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, University Hospital Hamburg-Eppendorf, Hamburg, Germany. 12. Department of Urology, Mayo Clinic, Rochester, MN, USA. 13. Department of Urology, Medical University of Vienna, Vienna, Austria; Departments of Pathology, The Jikei University School of Medicine, Tokyo, Japan; Division of Urology, Department of Special Surgery, The University of Jordan, Amman, Jordan; Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University of Texas Southwestern, Dallas, TX, USA; Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria; Department of Urology, Second Faculty of Medicine, Charles University, Prague, Czech Republic; European Association of Urology Research Foundation, Arnhem, Netherlands. Electronic address: shahrokh.shariat@meduniwien.ac.at.
Abstract
INTRODUCTION: There are questions regarding whether grade group (GG) 4 prostate cancer (PC) is heterogeneous in terms of prognosis. We assessed prognostic differences in PC patients within GG 4 treated with radical prostatectomy (RP). MATERIAL AND METHODS: Biochemical recurrence (BCR)-free, cancer-specific, and overall survival were analyzed in 787 PC patients with GG 4 based on RP pathology (Gleason score (GS) 3 + 5: 189, GS 4 + 4: 500, and GS 5 + 3: 98). Logistic regression analysis was performed to assess factors predictive of high-risk surgical pathological features. Cox regression models were used to evaluate potential prognostic factors of survival. RESULTS: Within a median follow-up of 86 months, 378 patients (48.0%) experienced BCR and 96 patients (12.2%) died, 42 of whom (5.3%) died of PC. GS 5 + 3 was significantly associated with worse BCR-free and cancer-specific survival, as well as higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates, than GS 3 + 5 and higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates than GS 4 + 4 (P < 0.05). GS 4 + 4 was significantly associated with worse BCR-free survival and higher extraprostatic extension, and non-organ-confined disease rates than GS 3 + 5 (P < 0.05). Inclusion of the different Gleason patterns improved the discrimination of a model for prediction of all survival outcomes compared to standard prognosticators. CONCLUSIONS: There is considerable heterogeneity within GG 4 in terms of oncological and surgical pathological outcomes. Primary and secondary Gleason patterns should be considered to stratify high-risk PC patients after RP.
INTRODUCTION: There are questions regarding whether grade group (GG) 4 prostate cancer (PC) is heterogeneous in terms of prognosis. We assessed prognostic differences in PC patients within GG 4 treated with radical prostatectomy (RP). MATERIAL AND METHODS: Biochemical recurrence (BCR)-free, cancer-specific, and overall survival were analyzed in 787 PC patients with GG 4 based on RP pathology (Gleason score (GS) 3 + 5: 189, GS 4 + 4: 500, and GS 5 + 3: 98). Logistic regression analysis was performed to assess factors predictive of high-risk surgical pathological features. Cox regression models were used to evaluate potential prognostic factors of survival. RESULTS: Within a median follow-up of 86 months, 378 patients (48.0%) experienced BCR and 96 patients (12.2%) died, 42 of whom (5.3%) died of PC. GS 5 + 3 was significantly associated with worse BCR-free and cancer-specific survival, as well as higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates, than GS 3 + 5 and higher positive surgical margin, lymph node metastasis, extraprostatic extension, and non-organ-confined disease rates than GS 4 + 4 (P < 0.05). GS 4 + 4 was significantly associated with worse BCR-free survival and higher extraprostatic extension, and non-organ-confined disease rates than GS 3 + 5 (P < 0.05). Inclusion of the different Gleason patterns improved the discrimination of a model for prediction of all survival outcomes compared to standard prognosticators. CONCLUSIONS: There is considerable heterogeneity within GG 4 in terms of oncological and surgical pathological outcomes. Primary and secondary Gleason patterns should be considered to stratify high-risk PC patients after RP.