CUA 2017: Predictors of Early Disease-Specific Mortality Among Patients with Prostate Adenocarcinoma and Bone Metastasis at Diagnosis

Toronto, Ontario ( Patients who present with metastatic prostate cancer represent an incurable subset of patients with prostate cancer. While management has traditionally been immediate initiation of androgen-deprivation therapy (ADT) alone, more recent studies have demonstrated evidence of concurrent administration of chemotherapy or androgen axis inhibitors (abiraterone).1,2,3,4

Identifying patients at highest risk of cancer-specific mortality in this cohort of patients may help better risk stratify receipt of these treatment options, especially as there is some suggestion that chemotherapy may be preferred for more aggressive disease. 

Utilizing the SEER database from the United States, the authors identified all men with metastatic prostate cancer, specifically focusing on men with bone metastases at the time of diagnosis, between 2010 and 2013. Of the 220,000 men with prostate cancer during this time frame, 8,040 men had bone metastases at the time of diagnosis. 

On further analysis, they identified 2,497 men (31.1%) who died of disease (prostate cancer specific mortality [PCSM]) and 5,543 men (68.9%) without PCSM (n=643 dead of other causes; n=4900 alive) over a median follow-up of 35 months (interquartile range [IQR] 34‒37). Patients with PCSM were more likely to be older, unmarried, have had biopsy Gleason Group (bGG) 5 disease or no prostate biopsy, and had concomitant PCa brain, liver, and lung metastases at diagnosis compared to patients without PCSM. 

On competing risks modelling, older age (HR 1.023), non-black/white race (HR 0.77), unmarried status (HR 1.10), higher prostate-specific antigen (PSA) (HR 1.005), bGG 4 (HR 1.53), bGG 5 (HR 2.18), no prostate biopsy (HR 2.97), and concomitant brain (HR 1.48), liver (HR 2.18), and lung metastases at diagnosis (HR 1.33) as predictive of PCSM.

An obvious limitation of the study is median follow-up of approximately 3 years. However, as this represents a relative aggressive pathology cohort, it likely captures a significant portion of the PCSM. 

Based on these results, while the entire cohort represents an aggressive pathology with high PCSM risk in the first 3 years, specifically men with prostate bGG 4‒5 disease presenting with bone and concomitant visceral metastasis should be considered for early, aggressive systemic therapy and/or clinical trials.

Presented By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre

Co-Authors: Thenappan Chandrasekar, Hanan Goldberg, Robert J. Hamilton, Neil E. Fleshner, Girish S. Kulkarni
Institution: University of Toronto

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto  Twitter: @tchandra_uromd at the 72nd Canadian Urological Association Annual Meeting - June 24 - 27, 2017 - Toronto, Ontario, Canada

1. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS.
N Engl J Med. 2015 Aug 20;373(8):737-46. doi: 10.1056/NEJMoa1503747. Epub 2015 Aug 5.

2. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AW, Parker CC, Russell JM, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O'Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MK; STAMPEDE investigators.

3. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O'Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR; STAMPEDE Investigators.
N Engl J Med. 2017 Jun 3. doi: 10.1056/NEJMoa1702900. [Epub ahead of print]

4. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. N Engl J Med. 2017 Jun 4. doi: 10.1056/NEJMoa1704174. [Epub ahead of print]