ESMO 2024: A New Prognostic Model of Overall Survival (OS) in Patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC)

(UroToday.com) The 2024 European Society of Medical Oncology (ESMO) Annual Congress held in Barcelona, Spain was host to the presentation of the poster 1615. Dr. Susan Halabi presented a new prognostic model of overall survival in patients with metastatic hormone sensitive prostate cancer (mHSPC).

Dr. Halabi began her poster presentation by noting the limited research on prognostic factors in patients with mHSPC. Previous findings have identified disease volume (High vs. low) and metastatic diagnosis status (synchronous vs. metachronous) as important prognostic factors for overall survival (OS).1,2 In this presentation, the authors shared a validated prognostic model of OS in patients with de novo mHSPC.

Data from four randomized phase III trials comparing treatment regimens (standard of care (SOC) vs SOC plus docetaxel) was utilized for building and validating the prognostic model of OS. For this model OS was defined as time between date of randomization to date of death/or last follow-up.

Dr Halabi and colleagues included only variables with a missing rate of less than 50% in at least one of the four trials, they used multiple imputations to handle missing values. The variables of interest for the model were: 

  • Age
  • ECOG performance status (PS)
  • Prior radical prostatectomy
  • Prior radiation therapy
  • Gleason score
  • Site of metastases
  • Number of bone metastases
  • Opioid analgesic use
  • Disease volume
  • M1 metastatic diagnosis
  • Hemoglobin
  • Albumin
  • PSA
  • Alkaline phosphatase.

The primary endpoint of the study was overall survival (OS), defined as the interval from the date of randomization to the date of death or last follow-up. The analysis focused on de novo patients (synchronic), and the proportional hazards model was used to fit the data. To handle missing data, multiple imputation by chained equations (MICE) was employed. Predictive accuracy was assessed using the time-dependent area under the receiver operating characteristic curve (tAUC), which was computed based on testing sets from the STAMPEDE trial.

They utilized two randomized trials (CHAARTED1 and GETUG-152 for developing the model and they employed a proportional hazards model where the final model was constructed based on the augmented training set incorporating two risk scores from trial-specific models.

They validated the fitted model using two comparisons from the STAMPEDE trial (SOC vs. SOC + docetaxel (A vs C) and SOC vs. SOC + zoledronic acid+ docetaxel (A vs E).

The development of this model included 2,234 patients. The median age was 64.6 years, 71.2% had an ECOG PS of 0, all had de-novo metastases (synchronic) and 63.3% had high disease volume. The baseline characteristics are shown in the table below:

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The following Kaplan-Meier graphic shows the almost overlapping OS curves between the four trials included for this OS analysis.

image-2.jpg

Disease volume, ECOG PS, age, opioid use, alkaline phosphatase, PSA, and hemoglobin were identified as important prognostic factors of OS.

image-3.jpg

In the STAMPEDE trial, two specific comparisons were analyzed:

  1. SOC vs. SOC + Docetaxel (Comparison A vs. C)
  2. SOC vs. SOC + Zoledronic Acid + Docetaxel (Comparison A vs. E)

For these comparisons, the time-dependent area under the receiver operating characteristic curve (tAUC) was calculated to measure predictive accuracy. The tAUCs for the two STAMPEDE testing sets were 0.73 (95% CI, 0.71-0.77) and 0.71 (95% CI, 0.67-0.74), indicating good predictive accuracy.

The figures below illustrate overall survival (OS) in the two comparison sets, stratified by two and three prognostic risk groups.

A vs. C

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image-5.jpg

A vs. E 

 

image-6.jpg

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The forest plot of tAUCs by subgroups confirmed high-volume disease as one of the strongest predictors for OS (tAUC 0.66, 95% CI 0.64-0.70).

image-8.jpg

Dr Halabi wrapped up her presentation by delivering the following messages:

  • The prognostic model identified High-volume disease as the strongest predictor of OS

  • This model offers the potential for classifying patients into three risk groups which could be useful in selecting men in future mHSPC trials. The model offers moderate discriminative ability with tAUC ranging from 0.68-0.72 by treatment and in validation sets

  • This prognostic model is only to be applied to de novo mHSPC patients

  • The Model needs to be externally validated in contemporary patients treated with ADT and ARPI

Presented by: Susan Halabi, PhD, Professor of Biostatistics & Bioinformatics Chief, Division of Biostatistics, Duke Cancer Institute, Durham, NC

Written by: Julian Chavarriaga, MD – Urologic Oncologist at Cancer Treatment and Research Center (CTIC) Luis Carlos Sarmiento Angulo Foundation via Society of Urologic Oncology (SUO) Fellow at The University of Toronto. @chavarriagaj on Twitter during the 2024 European Society of Medical Oncology (ESMO) Annual Meeting, Barcelona, Spain, Fri, Sept 13 – Tues, Sept 17, 2024. 

References:

  1. 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. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46.
  2. Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):149-58.
  3. 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. 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 Mar 19;387(10024):1163-77.