Early Detection of Prostate Cancer using PSMA PET

The use of PSMA PET has expanded from the detection of recurrent prostate cancer (PCa) to the initial staging of PCa. The use of PSMA PET as a tool for the detection of primary PCa is still an area under exploration, which was discussed in Part 1 of this thesis. In Chapter 1, the diagnostic performance of 18F-DCFPyL PET/CT to localize primary PCa within the prostate gland was assessed. The RARP pathology results were compared with the localization of PSMA expression on PET/CT. Using this comparison, the potential for PSMA-guided targeted-prostate biopsy was explored. After the analysis of 30 patients that received both a RARP and a 18F-DCFPyL PET/CT, an accurate per-patient localization (93%) of csPCa was found within the prostate, when following the potential biopsy advice of the nuclear physician. Moreover, the sensitivity of detecting seminal vesicle invasion using 18F-DCFPyL PET/ CT was 75.0%, with only a 20.0% sensitivity for detecting extracapsular growth. Based on these results, 18F-DCFPyL PET/CT proves to be promising for guiding PSMA-targeted biopsies and has moderate local staging ability. The previously described chapter discussed the detection of local PCa in a biopsy confirmed cohort. In Chapter 3, the hypothesis that PSMA PET can detect local PCa was prospectively analyzed in a biopsy-naïve cohort. In 60 men with an elevated PSA level of 20-50 ng/mL that were scheduled for biopsies, a 18F-DCFPyL PET/CT was performed resulting in PSMA targeted biopsies. A very high detection rate for PCa was observed by combined systematic and targeted biopsy, as well as for targeted biopsy only. Therefore, using PSMA PET as single imaging modality, a substantial number of diagnostic MRI scans could be avoided, while adequately targeting lesions suspicious for PCa and staging patients for metastases. In men with metastatic disease on imaging at initial presentation, the number of prostate biopsies could be substantially reduced by taking targeted biopsies only. Part 2 The use of PSMA PET/CT for initial staging is already described for 68Ga-PSMA tracers in the literature, Part 2 shows the applicability for 18F-PSMA tracers. Chapter 5 investigated the accuracy of 18F-DCFPyL PET/CT to detect pelvic lymph node PCa metastases. In a prospective cohort study, the accuracy of 18F-DCFPyL PET/CT imaging for the detection of lymph-node metastatic disease was investigated in men with intermediate and highrisk PCa undergoing RARP and an extended pelvic lymph node dissection (ePLND). In 117 investigated patients, a limited sensitivity of 41.2% was detected for 18F-DCFPyL PET/CT, at an excellent specificity of 94.0%. Based on these results, 18F-DCFPyL PET/CT imaging should not replace a diagnostic ePLND. Part 3 In the final part of this thesis, the application of semi-quantitative measurements for PET/CT was investigated. Chapter 8 aimed to explore the previously mentioned clinical ‘biomarker’ potential of SUV to predict tumor characteristics. The intratumoral SUVmax was measured to predict tumor characteristics in patients that received a PSMA PET/CT as an initial staging tool prior to a radical prostatectomy. A total of 318 patients were evaluated in this retrospective study and a highly significant association was found between median intraprostatic SUV on PET/CT and conventional prognostic tumor characteristics, such as pathological ISUP score and pN-stage in intermediate- to high-risk PCa patients. Moreover, SUV remained an independent predictive factor for pN1-status on multivariable analysis. Therefore, the SUV as measured on PSMA PET/CT might be of value for the pre-operative or pre-biopsy prediction of tumor aggressiveness features. The prognostic value of SUV by PSMA PET/CT may have the potential to be a “biomarker” in the primary staging of intermediate- to high-risk PCa, or in its screening for biopsies.