Marieke van Son

68 CHAPTER 4 opsies were guided by MRI findings [50]. Adding mp-MRI information to subsequent TPM biopsies seems to achieve the highest diagnostic accuracy, with a sensitivity and specificity of 97% and 61%, a positive predictive value of 83% and a negative pre- dictive value of 91% [64]. Different approaches to achieve biopsy under MRI-guidance (i.e. in-bore, MRI-TRUS fusion or cognitive registration) yield similar detection rates of clinically significant prostate cancer [65]. Interestingly, the definition of clinically significant cancer differs between studies, ranging from Gleason score 6 and cancer core length >3 mm to Gleason score ≥4+3. In the radiorecurrent setting, prostate biopsy evaluation is hampered by radiation effects, which sometimes mimic higher grade disease. Approximately 30% of inde- terminate biopsies seem to resolve into negative disease status. On the other hand, local failure can also be interpreted as radiation effect and indeterminate biopsies should therefore not be considered negative. Furthermore, delayed tumor regression may cause false positives. Biopsies should therefore not be taken before 24 months of follow-up [66]. Even after two years, routine post-radiotherapy biopsies are of lim- ited added value to regular PSA-testing, and should only be considered in case of biochemical failure [67]. According to the EAU guidelines, biopsy after radiotherapy is only indicated if local recurrence affects treatment decisions [68]. In case of localized recurrence, one could argue that biopsies might aid in the se- lection of patients for focal salvage treatment. A study comparing cognitive target- ed biopsies with TPM biopsies showed that targeted biopsies had similar or at most 10% less detection rates, depending on the definition of clinically significant cancer. Targeted biopsies were efficient, requiring fewer biopsies compared to TPM biopsies for detection of clinically significant disease [69]. However, clinical significance was determined based on either maximum cancer core length or Gleason score. Since the effect of altered architecture from previous radiotherapy on the Gleason score is poorly understood, it does not seem appropriate for grading radiorecurrent lesions [70-72]. Validation studies on the use of the Gleason scoring system in the radiorecurrent set- ting are lacking in the current available literature. Furthermore, there seems to be no consensus on the Gleason score definition for clinically significant disease. Histological confirmation of recurrence is therefore limited (i.e. adenocarcinoma yes/no) and does not provide any information on the clinical significance (tumor aggressiveness) of the recurrent lesion. With advancements in imaging modalities as outlined above, and the burden of in- vasive biopsy procedures on patients, it is questionable whether these biopsies are mandatory for adequate disease assessment. There is no literature describing the accuracy of combined mp-MRI and PET-CT with pathology verification in the radio- recurrent setting. Currently, we are investigating a cohort of patients with a positive recurrent lesion on (68)Ga-PSMA-PET/CT and at least one mp-MRI sequence, who underwent subsequent MRI-targeted biopsies, to determine the added value of histo- logic verification for adequate disease assessment.