AUA 2024: Development of a Novel Risk Stratification for Prostate Cancer Patients Candidate to Radical Prostatectomy Staged with Preoperative PSMA-PET: The Key Role of Molecular Imaging

( The 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX between May 3 and May 6, 2024, was host to the prostate cancer podium staging session. Dr. Francesco Barletta used retrospective data from a multicenter collaboration including 9 centers across Europe. He presented a novel risk stratification model for prostate cancer patients’ who are candidates for radical prostatectomy (RP) and had been staged with preoperative PSMA-PET.

Dr. Barletta began by discussing that preoperative risk stratifications are of utmost importance for clinical decision-making in prostate cancer (PCa) patients. Despite the development of novel risk groups in recent years, no stratification scheme includes PET-PSMA data, which could identify patients more likely to experience biochemical failure (BCF). 

This study included data from 707 intermediate/high-risk PCa patients treated with RP and extended pelvic lymph node dissection (ePLND) who underwent preoperative PSMA-PET. The primary outcome was early BCF, which was defined as either:

  • PSA ≥0.1 at 6 weeks of RP
  • Increasing PSA ≥0.2 within 2 years after surgery

They used multivariable Cox-regression models adjusting for:

  • PSA (<10 vs 10–20 vs >20 ng/ml)
  • Multiparametric MRI (mpMRI) (non-organ-confined stage)
  • Biopsy grade group (GG 1-2 vs 3 vs 4-5)
  • Percentage of positive biopsy cores (<50 vs ≥50%)
  • PET-PSMA findings (miN0 vs miN1) 

A score was assigned to each individual feature according to Cox-derived coefficients. Patients were stratified in intermediate (0-2 points), high (3-5 points), or very-high (≥6 points) risk groups. They used Harrel’s c-index to test for discrimination, and decision curve analysis (DCA) to determine the clinical net benefit associated with the new stratification scheme comparing it with available ones. They utilized the EAU risk groups and the risk classification reported by Mazzone et al.1 to compare risk stratification with their newly proposed novel risk stratification system.

Patient characteristics are shown in the table below. To highlight 14% of patients had molecular imaging (mi) miN1 stage, and most (60%) had ISUP grade 4-5 disease.
Dr. Barletta demonstrated that when patients included in the study were categorized according to Mazzone vs. EAU risk groups, there was some degree of variation: in the Mazzone risk groups, 19% were intermediate risk, 72% high risk, and 9% were very high risk; using the EAU risk groups, 32% were intermediate risk and 68% were high risk. miN1 stage was present in 14% of their patients, and not surprisingly, at MCR, the miN1 stage represented the strongest predictor for BCF (HR 3.9, 95% CI 2.5-5.9, p < 0.001).
MCR models predicting BCR
Following stratification based on Cox-derived scores, their new model categorized 39% of patients as intermediate risk, 28% as high risk, and 33% as very high risk. The 2-year BCF rates were 91% for intermediate-risk patients, 79% for high-risk patients, and 58% for very high-risk patients, based on their novel risk groups.kaplan meier plots depicting biochemical failure-FS according to the novel risk classification
This risk classification demonstrated superior discrimination compared to the Mazzone EAU and EAU risk classifications (c-index: 73% vs 60% vs 61%, respectively). In decision curve analysis (DCA), the novel risk stratification exhibited greater net benefit when compared to the existing risk classification models.decision curve analysis (DCA), the novel risk stratification exhibited greater net benefit when compared to the existing risk classification models
Dr. Barletta wrapped up his presentation concluding that their newly developed risk classification tool including preoperative PSMA-PET outperforms available risk groups (EAU risk groups and Mazzone et al.) to predict early BCF after RP. 

Presented by: Francesco Barletta, MD, Urology Resident and Clinical Researcher, The IRCCS Ospedale San Raffaele, Milan, Italy

Written by: Julian Chavarriaga, MD - Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @chavarriagaj on Twitter during the 2024 American Urological Association (AUA) annual meeting held in San Antonio, TX between May 3rd and May 6th, 2024

  1. Mazzone E., Gandaglia G., Ploussard G., et al. Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups. Eur Urol. 2022;81(2):193-203