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ASTRO 2021: Prognostic Significance of the Risk of Non-Localized Disease on PSMA/PET: Comparative Performance of a Novel, PSMA/PET-Derived Risk Stratification Tool for High-Risk Prostate Cancer in a Large, Multi-Institutional Cohort

(UroToday.com) The 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting’s included a session on biomarkers and salvage radiotherapy and discussion by Dr. Ting Martin Ma regarding the prognostic significance of the risk of non-localized disease on PSMA/PET CT.

PSMA PET/CT is a novel molecular and functional imaging modality for detecting prostate cancer, with greater accuracy (92% vs 65%), sensitivity (95% vs 38%), and specificity (98% vs 91%) than conventional imaging in detecting pelvic nodal or distant metastatic disease. When performed after conventional imaging, PSMA has been reported to lead to a change in stage in 22% of patients, including nodal upstaging to 18% and metastatic upstaging in 8% of patients. Dr. Ma and colleagues recently developed a nomogram for predicting the probability of nodal and metastatic disease detected by PSMA PET/CT in patients with newly diagnosed cN0M0 high-risk prostate cancer.1 Key predictors in this nomogram included iPSA, percent core positive on systematic biopsy, Gleason grade group, and cT stage. Overall, 21.1%, 8.9%, and 23.9% of patients experienced nodal, metastatic, and overall upstaging, respectively, without histologic confirmation. The nomogram was internally validated with a tenfold cross-validated area under the receiver operating characteristic curve estimated at 0.74 (95% CI 0.67–0.82). In this cohort, 90% of patients who had a nomogram-estimated risk below the cutoff of 22% for overall upstaging could have been spared PSMA PET/CT as the model correctly predicted no upstaging. This PSMA risk calculator is available online at: https://www.uclahealth.org/radonc/psma-risk-calculator

Currently available prostate cancer risk-stratification tools available are as follows:

  1. CAPRA score:2 based on age, iPSA, Gleason score, cT stage, and percent positive cores
  2. MSKCC nomogram:3 based on age, iPSA, Gleason score, cT stage, and percent positive cores
  3. STAR-CAP:4 based on age, iPSA, Gleason score, cT stage, cN stage, and percent positive cores. The 10-year c-index for this tool is 0.796, which outperformed the AJCC 8th edition of staging, CAPRA, and NCCN risk grouping.

The objective of this study presented by Dr. Ma and colleagues at ASTRO 2021 was to determine the prognostic performance of the PSMA nomogram in predicting clinical outcomes, such as biochemical recurrence, distant metastasis, prostate cancer specific mortality, and overall survival. A secondary objective was to compare the prognostic performance of the PSMA nomogram to existing risk-stratification tools.

This was a multi-institutional cohort of 5,275 cN0M0 patients with high- and very high-risk prostate cancer from 15 tertiary centers treated between 1995 and 2018 for which biochemical recurrence, distant metastasis, prostate cancer specific mortality, and overall survival outcomes were available. Secondly, this study included a SEER cohort of 23,989 patients with high- and very high-risk prostate cancer treated between 2010 and 2016 for which prostate cancer specific mortality and overall survival outcomes were available (but biochemical recurrence and distant metastasis outcomes were not available). Finally, this study also included a NCDB cohort of 88,909 patients with high- and very high-risk prostate cancer treated (both surgery and radiotherapy patients were included) between 2010-2016, for which overall survival outcomes were available.

In the multi-institutional cohort, the PSMA nomogram is predictive of clinical endpoints with the c-index for predicting the 8-year clinical endpoints as follows:

  • Biochemical recurrence: 0.63 (95% CI 0.61-0.65)
  • Distant metastasis: 0.69 (95% CI 0.66-0.71)
  • Prostate cancer specific mortality: 0.71 (95% CI 0.67-0.75)
  • Overall survival: 0.60 (95% CI 0.57-0.62)

 

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 The PSMA nomogram risk was also significantly prognostic for all clinical endpoints in different treatment subgroups—radical prostatectomy, external beam radiotherapy, and external beam radiotherapy + brachytherapy, except performance was lower for the external beam radiotherapy + brachytherapy group. Additionally, four nomogram defined groups have distinct risk profiles corresponding to PSMA PET/CT upstaging risks of <= 14%, 14-27%, 27-41%, and >41%:

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This nomogram was also predictive in SEER and NCDB, with the following 5-year c-indices:

  • SEER: prostate cancer specific mortality (0.71, 95% CI 0.69-0.74), and overall survival (0.61, 95% 0.59-0.62)
  • NCDB: overall survival (0.62, 95% CI 0.61-0.63)

 Furthermore, in the multi-institutional cohort, the PSMA nomogram outperformed STAR-CAP, CAPRA and the MSKCC nomogram for all endpoints (p < 0.01), except performance was similar to STAR-CAP for prostate cancer specific mortality (p = 0.11).

Dr. Ma concluded this presentation of the comparative performance of a novel, PSMA/PET-derived risk stratification tool for high-risk prostate cancer with the following take-home messages:

  • The predicted risk of upstaging on PSMA PET/CT is linked with long-term clinical outcomes such as distant metastasis and prostate cancer specific mortality
  • PSMA nomograms showed improved risk-stratification, outperforming other models for all endpoints
  • Previously occult, non-localized disease may be the primary driver of outcomes in this high-risk patient population
  • This nomogram (available online) can also help select for patients most likely to benefit from PSMA PET/CT and/or treatment intensification

 

Presented by: Ting Martin Ma, MD, Department of Radiation Oncology, UCLA, Los Angeles, CA 

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2021 American Society for Radiation Oncology (ASTRO) Hybrid Annual Meeting, Sat, Oct 23 – Wed, Oct 27, 2021.

References:

  1. Ma TM, Gafita A, Shabsovich D, et al. Identifying the best candidates for prostate-specific membrane antigen positron emission tomography/computed tomography as the primary staging approach among men with high-risk prostate cancer and negative conventional imaging. Eur Urol Oncol. 2021 Feb 2021 [Epub ahead of print].
  2. Cooperberg MR, Hilton JF, Carroll PR, et al. The CAPRA-S Score: A straightforward tool for improved prediction of outcomes after radical prostatectomy. Cancer. 2011;117:5039-5046.
  3. Godoy G, Chong KT, Cronin A, et al. Extent of pelvic lymph node dissection and the impact of standard template dissection on nomogram prediction of lymph node involvement. Eur Urol. 2011;60(2):195-201.
  4. Dess RT, Suresh K, Zelefsky MJ, et al. Development and validation of a clinical prognostic stage group system for nonmetastatic prostate cancer using disease-specific mortality results from the International Staging Collaboration for Cancer of the Prostate. JAMA Oncol. 2020;6(12):1912-1920.