PSMA PET Agent Improves Recurrence Risk Assessment in Prostate Cancer

"PSMA PET is now the best imaging tool for prostate cancer. As it is still new, we need to learn how to use the information derived from PSMA PET for the best outcomes of patients," according to Thomas Hope, MD, a professor and vice chair of Clinical Operations and Strategy in the Department of Radiology at UCSF.

Prostate-specific membrane antigen (PSMA) PET agent 68GA-PSMA-11 appeared to improve assessments of potential biochemical recurrence-free survival (BCR-FS) prior to surgery in patients with intermediate- to high-risk advanced prostate cancer, according to findings from a follow-up study of a surgical cohort assessed in a phase 3 trial at the University of California, Los Angeles (UCLA; NCT03368547) and the University of California, San Francisco (UCSF; NCT02611882, NCT02919111)¹.

Of 277 patients who underwent PSMA PET prior to radical prostatectomy and pelvic lymph node dissection, 91 experienced BCR, which included a median prostate-specific antigen (PSA) of 0.25 ng/mL (interquartile range [IQR], 0.1-0.6) at the time of BCR. Among those with BCR, 42 had PSA persistence, and 11 received a secondary treatment more than 6 months after radical prostatectomy, which most included radiotherapy plus androgen deprivation therapy (ADT; n = 50/91), ADT alone (n = 13/91), and radiotherapy plus androgen targeted therapy (n = 12/91).

In terms of BCR-FS, the median survival was 45.3 months (95% CI, 25.1-not reached [NR]) among patients with high PSMA PET prostate uptake vs NR (95% CI, 37.3-NR) in those with low PSMA PET uptake (P = .012). The median survival was 9.0 months (95% CI, 4.9-38.0) in those with PSMA PET extraprostatic disease vs NR (95% CI, 45.3-NR) in those without (P <.0001).

The median survival was 37.3 months (95% CI, 22.6-NR) in patients with a presurgical Cancer of the Prostate Risk Assessment (CAPRA) score of at least 6 vs NR (95% CI, 44.7-NR) in those with a score of 0 to 5. (P = .0049). Moreover, the median survival was 17.1 months (95% CI, 11.6-38.0) in those with a postsurgical CAPRA-surgery (CAPRA-S) score of at least 6 vs NR (95% CI, NR-NR) in those with a score of 0 to 5. (P < .0001).

When adjusting for covariates, presurgical CAPRA score (HR, 1.2; 95% CI, 1.1-1.4; P = .003) and PSMA PET extraprostatic disease (HR, 2.6; 95% CI, 1.6-4.2; P <.0001) significantly correlated with BCR. Considering these 2 covariates together improved BCR risk assessment (c-statistic, 0.70; 95% CI, 0.64-0.75) compared with adjusting for presurgical CAPRA score alone (c-statistic, 0.63; 95% CI, 0.57-0.69; P <.0001). Additionally, adjusting for CAPRA-S score (HR, 1.4; 95% CI, 1.2-1.5; P <.0001) and PSMA-PET extraprostatic disease (HR, 1.6; 95% CI, 1.0-2.7; P = .05) in another model also significantly correlated with BCR.

“In patients with prostate cancer considered for surgery, PSMA PET can provide information on the risk of recurrence after surgery, before the surgery even happens,” lead study author Loïc Djaïleb, MD, PhD, said in a press release on these findings.² “The imaging tool improves personalized treatments by helping the urologist decide whether or not to perform surgery, and to guide the surgical plan and the follow-up management after surgery.”

Djaïleb is a visiting associate professor at the David Geffen School of Medicine at UCLA.

In this post hoc follow-up study, investigators assessed the diagnostic accuracy of 68GA-PSMA-11 in a surgical cohort of patients with intermediate- or high-risk advanced prostate cancer who are set to undergo radical prostatectomy from December 2015 to December 2019. Three blinded independent readers interpreted each 68GA-PSMA-11 scan via 2 vs 1 central majority rule. Investigators calculated CAPRA and CAPRA-S scores as 0 to 2 or low risk; 3 to 5 or intermediate risk; and 6 and above or high risk.

The primary end point was BCR-FS, which investigators defined as the period between surgery and the occurrence of BCR, or a PSA level of at least 0.2 ng/mL following radical prostatectomy or beginning secondary treatment at more than 6 months after surgery.

The median patient age was 67 years (IQR, 61-71), and patients had a median PSA of 11.26 ng/mL (IQR, 6.7-18.0) at baseline. Most patients had clinical T stage II disease or lower (64%), National Comprehensive Cancer Network high-risk disease (81%), and a CAPRA score of 6 to 10 (67%). After surgery, most patients were reported to have extracapsular extension (86%) in terms of histopathological local extension and positive pelvic lymph nodes (28%).

“PSMA PET is now the best imaging tool for prostate cancer. As it is still new, we need to learn how to use the information derived from PSMA PET for the best outcomes of patients,” co-senior author Thomas Hope, MD, a professor and vice chair of Clinical Operations and Strategy in the Department of Radiology at UCSF, concluded.²

References

1. L. Djaïleb, W.R. Armstrong, D. Thompson, et al. Presurgical 68Ga-PSMA-11 positron emission tomography for biochemical recurrence risk assessment: a follow-up analysis of a multicenter prospective phase 3 imaging trial. Eur Urol. Published online July 21, 2023. doi:10.1016/j.eururo.2023.06.022
2. PSMA PET imaging improves accuracy of predicting prostate cancer recurrence. News release. University of California, Los Angeles. July 25, 2023. Accessed July 26, 2023. https://shorturl.at/pCO39