EAU 2018: Variation in Prevalence of High and Low Volume Metastatic Prostate Cancer from the Original Comparison in the STAMPEDE Trial

Copenhagen, Denmark (UroToday.com) Early use of docetaxel with ADT has now become a standard of care in newly presenting hormone naïve metastatic (M1) prostate cancer based on several randomized clinical trials (RCTs) 1-4. However, there is uncertainty as to whether the beneficial effect is seen in all patients, including those with “low volume” disease as defined by the CHAARTED trial3. A volumetric effect was not seen in retrospective analysis of the GETUG-AFU-15 trial2 and the larger STAMPEDE trial1 did not demonstrate heterogeneity of effect by type of baseline metastasis, although prospective quantification of metastatic burden was not performed1. Dr. Hoyle and colleagues presented results assessing variation in prevalence of high and low volume metastatic prostate cancer for patients in the STAMPEDE trial. The aims of the study were to evaluate the prevalence of high and low volume metastatic disease between cited stratification definitions within the published control and docetaxel treatment arms, and to evaluate the impact on volume prevalence when non-regional lymph nodes + bone metastasis are included as a high-volume feature.

For this study, bone scintigraphs were centralized and retrospectively analyzed for M1 patients randomized between October 1, 2008 and March 31, 2013 to the STAMPEDE control arm (A) or a docetaxel-containing arms (C and E). 

Variation Metastatic Prostate Cancer STAMPEDE

Metastatic disease burden was classified according to the CHAARTED volume definition3, as well as the Yossepowitch5 and LATITUDE6 trial definitions:

Variation Metastatic Prostate Cancer 2

For this study, 1,208 patients were identified meeting the inclusion criteria, and 816 patients had incomplete clinical information for imaging centralization making up the study cohort. Metastatic status distribution included: M1a (n=117), M1b (n=579, 78%), M1c (n=120). 

There was significant variation in percent prevalence in high and low volume STAMPEDE trial patients when stratified by alternative definitions:

  • Yossepowitch: 23.4% low-volume; 76.6% high-volume
  • Yossepowitch (with non-regional lymph nodes and bone metastasis in high-volume): 21.4% low-volume; 78.6% high-volume
  • CHAARTED: 40.2% low-volume; 59.8% high-volume
  • CHAARTED: (with non-regional lymph nodes and bone metastasis in high-volume): 35.8% low-volume; 64.2% high-volume
  • LATITUDE: 44.9% low-volume; 55.1% high-volume
  • LATITUDE (with non-regional lymph nodes and bone metastasis in high-volume): 42.2% low-volume; 57.8% high-volume
The authors concluded that the various volumetric classification systems result in substantial discrepancies in the proportions classed as high or low-volume risk. Minimal impact on volume ratio prevalence was seen when co-existing non-regional lymph nodes and bone metastasis were included as high-volume features. Prevalence discrepancy between cited definitions may explain the variations in “volume effects” observed in the current literature.


Presented by: Alex P. Hoyle, Christie NHS Foundation Trust, Manchester, United Kingdom

Co-Authors: Ali A, Douis H, Sydes M, James N, Clarke N

References: 
1. James ND, Sydes MR, Clarke NW, et al. 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. Lancet. 2016;387(10024):1163-1177.
2. Gravis G, Boher JM, Joly F, et al. Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial. Eur Urol. 2016;70(2):256-262.
3. Sweeney CJ, Chen YH, Carducci M, et al. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015;373(8):737-746.
4. Kyriakopoulos CE, Chen YH, Carducci MA, et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: Long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol 2018 Jan 31 [Epub ahead of print].
5. Yossepowitch O, et al. The natural history of noncastrate metastatic prostate cancer after radical prostatectomy. Eur Urol 2007;51(4):940-948.
6. Fizazi K, Tran N, Fein L, et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N Engl J Med. 2017;377(4):352-360.

Written by: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, twitter: @zklaassen_md at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark

Read More:
Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy - STAMPEDE Trial

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer - CHAARTED Trial

Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer - LATITUDE
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