Towards clinical implementation of PSMA PET/CT in prostate cancer

In Chapter 2 we investigated the role of PSMA-PET detecting pelvic lymph node metastatic disease, and assessed whether we could select patients who may be candidates to withhold an extended pelvic lymph node dissection (ePLND). We found patients with intermediate risk PCa and a radiological T-stage <rT3 on mpMRI are potential candidates to withhold ePLND in the presence of a “negative for lymph node metastases” PSMA-PET scan. In Chapter 3, we aimed to identify predictors of early oncological outcomes in patients undergoing RARP and ePLND for localized prostate cancer. We observed that higher initial PSA values, biopsy Grade Group ≥4, ≥rT3 disease on MRI and lymph node metastases on PSMA-PET (molecular imaging (mi)N1) were significant predictors of early biochemical progression after RARP. In Chapter 4, we found that, in patients with pN1-disease, those with miN1 disease on staging PSMA-PET have an impaired prognosis compared to patients with a negative for metastases staging PSMA-PET. Apparently, miN1-disease is a significant predictor for biochemical progression after surgery, independent of surgical pathology results. Besides, the majority of patients with pN1-disease had biochemical progression within 2 years after surgery. In Chapter 5, we concluded that the addition of PSMA-PET to the previously developed nomograms for predicting pN1-disease showed substantially improved predictive performance, which suggests that PSMA-PET is likely a future candidate for a modern predictive nomogram. Consequently, in Chapter 6, the Amsterdam-Brisbane-Sydney nomogram was developed and validated in an external international validation cohort. We found that the validated Amsterdam-Brisbane-Sydney-nomogram performs superior to the Briganti-2017 and MSKCC-nomogram, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate and high risk PCa. In Chapter 7, we investigated the role of PSMA-PET in patients with biochemical persistence (i.e., persistently measurable PSA) after RARP. In our study, which included a total of 150 patients, we found that a high proportion of patients (59%) had metastatic lesions on PSMA-PET outside the prostatic fossa (i.e., metastatic disease). In Chapter 8, we assessed the role of 18F-DCFPyL PET/CT, a PSMA-tracer, on management decisions in patients with BCR after definitive treatment. We concluded that 18F-DCFPyL PET/CT had a significant impact on the intended management of patients with biochemically recurrent hormone-sensitive prostate cancer. In 40.7% of cases, a preferred treatment change based on the PSMA-PET findings was reported. Chapter 9 focused on the role of PSMA-PET in the evaluation of response of patients who underwent SRT to the prostatic fossa for BCR prostate cancer after RARP. On multivariable analysis, evidence of local recurrent disease on PSMA-PET was significantly associated with developing a treatment response, compared to patients with a negative PSMA-PET. In Chapter 10, we directly compared the oncological outcome following SRT of a patient cohort that underwent PSMA-PET imaging prior to SRT with that of a patient cohort that did not have PSMA-PET imaging before SRT. To compare both cohorts, case-control matching was performed. After case-control matching, 216 patients were matched in both cohorts (108 patients per cohort). In the patient cohort without PSMA-PET/CT prior to SRT, 23 of 108 patients (21%) had biochemical progression of disease at 1 year after SRT, compared with nine (8%) who underwent restaging PSMA-PET/CT prior to SRT (p = 0.007). In Chapter 11 we aimed to develop a novel nomogram predicting the early oncological outcomes of patients undergoing SRT, who were priorly restaged with PSMA-PET imaging. The final nomogram consisted of PSA-value at initiation of SRT, pathological Grade Group, surgical margin status, PSA doubling time, PSMA-PET findings and the presence of BCP after RARP, showing good performance (AUC 0.72 95%CI 0.64-0.79).