The key finding of our study is the demonstration that a significant proportion of men suitable for active surveillance had management diverted to intervention based on combined MRI and PSMA PET findings. From the 30 men who met the eligibility criteria for active surveillance, 15 (50%) men had concerning features on PSMA PET including moderate-marked (SUV max >5) PSMA expression of the index lesion, MRI occult lesion or evidence of EPE. From the 16 men that underwent a robotic assisted radical prostatectomy, 10 (33.3%) men harboured at least one adverse pathological feature including the presence of cribriform architecture, intraductal pattern, extracapsular extension and/ or upgrade in grade group. Recent population-based studies support our findings, demonstrating upgrading rates ranging from 36.4%-46% and 24-24.7% for men with low risk and favourable intermediate risk prostate cancer respectively (15). Similarly, Mufarrij et al. reported 45.9%-47.2% of cases were pathologically upgraded to a Gleason score ≥ 7 (16).
Introduction of multiparametric MRI (mpMRI) and MRI targeted biopsies has transformed diagnosis and treatment of prostate cancer. Our study identified that for men who had GG ≥2 cancers either on biopsy or prostatectomy, 15 had lesions with a PI-RADS score of 4/5. Similarly a meta-analysis of 17 studies involving men with suspected or biopsy-proven PCa, the average PPVs for GG ≥2 cancers of lesions with a PI-RADS score of 3, 4 and 5 were 16% (7–27%), 59% (39–78%), and 85% (73–94%), respectively (17). Furthermore, the PRECISION trial compared MRI targeted prostate biopsy with standard template guided biopsy reporting an increase in the detection rate of clinically significant disease from 26% to 38%, while reducing the detection of clinically insignificant disease from 22% to 9% (18). Several guidelines reflect these findings and strongly recommend the use of mpMRI in the re-evaluation of men on Active Surveillance(19, 20).
Recently, prostate-specific membrane antigen (PSMA) PET/CT has been well-explored and successfully translated for the clinical diagnosis of PCa (3, 21). PSMA expression is strongly correlated with Gleason score of the primary tumour (7). Moreover, studies have evaluated the diagnostic value of using a combination of PSMA PET and prostate MRI to detect prostate cancer. A retrospective analysis of men with low to intermediate-risk PCa found that PSMA identified GG³ 2 malignancies more frequently than GG 1 with sensitivity of 88% versus 18% (6). This is further supported by Raveenthiran et al. that retrospectively analysed 1123 men and identified 92% of csPCa by combining mpMRI and (68)Ga-PSMA PET/CT (22). These findings were confirmed in the prospective multicentre trial (PRIMARY trial)(23). The PRIMARY trial confirmed 90% sensitivity of PSMA PET/CT for detecting csPCa. It also demonstrated the compelling advantage of PSMA in men with negative or equivocal MRI. On biopsy, 28% of men with PI-RADS 2 and 47% with PI-RADS 3 had csPCa, with 90% of these malignancies identified by PSMA(5).
There are several limitations to this study, including the small population size and retrospective single centre design. Not all men diagnosed with prostate cancer meeting criteria for active surveillance underwent a PSMA PET/CT and this has the potential to create a selection bias that might overstate the extent to which management was altered. However, the majority of men who underwent a PSMA PET/CT had GG2 on their biopsy which represents a cautious approach for these patients when considering management by AS. It is also recognised that not all prostate cancers will express PSMA and could therefore result in a negative PSMA PET but given that this represents a small percentage of cases, it is unlikely to significantly alter the findings and conclusions of this study.