LOS ANGELES — Low-volume, nonlocalized prostate cancer that was occult on conventional imaging often can be detected with prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT).
A new study asked: What are the long term clinical implications of PSMA PET/CT upstaging?
UCLA-led researchers sought to evaluate the prognostic significance of a nomogram that models an individual’s risk of regional or metastatic upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools. The VA Greater Los Angeles Healthcare System participated in the study.
An article in JAMA Network Open discussed results of the cohort study, which included patients diagnosed with high-risk or very high-risk prostate cancer from April 1995 to August 2018. For purposes of the multinational study, which was conducted at 15 centers, high-risk or very high-risk prostate cancer was defined as that with prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup. Data were analyzed from December 2020 to March 2021.1
The 5,275 participants received curative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT) or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy. The researchers calculated PSMA upstage probability from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM) and overall survival (OS).
Patients had a median (IQR) age of 66 and 55% were treated with RP, 32% with EBRT and 14% with EBRT plus BT. Their median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL, while 76% had Gleason grade 8 to 10 disease and 14% had stage T3 to T4 disease. The study’s median (IQR) follow-up was 5.1 (3.1-7.9) years, with 23% of patients followed up for at least eight years.
“Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer,” the authors wrote. “PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P < 0.001). The PSMA nomogram outperformed existing risk-stratification tools, except for similar performance to Staging Collaboration for Cancer of the Prostate (STAR-CAP) for PCSM (e.g., DM: PSMA, 0.69 [95% CI, 0.66-0.71] vs STAR-CAP, 0.65 [95% CI, 0.62-0.68]; P < .001; Memorial Sloan Kettering Cancer Center nomogram, 0.57 [95% CI, 0.54-0.60]; P < .001; Cancer of the Prostate Risk Assessment groups, 0.53 [95% CI, 0.51-0.56]; P < .001). Results were validated in secondary cohorts from the Surveillance, Epidemiology, and End Results database and the National Cancer Database.”
The authors noted that their findings suggest that “PSMA upstage probability is associated with long-term, clinically meaningful end points. Furthermore, PSMA upstaging had superior risk discrimination compared with existing tools. Formerly occult, PSMA PET/CT-detectable nonlocalized disease may be the main driver of outcomes in high-risk patients.”
- Xiang M, Ma TM, Savjani R, Pollom EL, et. al. Performance of a Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography-Derived Risk-Stratification Tool for High-risk and Very High-risk Prostate Cancer. JAMA Netw Open. 2021 Dec 1;4(12):e2138550. doi: 10.1001/jamanetworkopen.2021.38550. PMID: 34902034.
