Improving Prostate Cancer Diagnostics: drawing insights from real-world data

The thesis examines the complex diagnostic process for prostate cancer (PCa), highlighting its frequent association with unnecessary diagnostics, overdiagnosis, and overtreatment. Conducted in collaboration with the Prostate Cancer Network Netherlands, the studies aim to assess current diagnostic methods and identify areas for improvement.

The initial chapters explore risk stratification and metastatic screening. Personalized risk calculators, like the Rotterdam Prostate Cancer Risk Calculator (RPCRC)-3/4 and -MRI, are intended to minimize unnecessary diagnostics. However, validation results revealed that RPCRC-3/4 underestimates the risk of clinically significant (cs)PCa, potentially missing 18.3% of cases. This discrepancy highlights the need for thorough population-specific evaluations before implementing risk calculators.
Chapters 3, 4, and 5 evaluate prostate biopsy techniques. Transperineal prostate biopsies, compared to transrectal biopsies, result in fewer complications and greater histopathological concordance post-radical prostatectomy (odds ratio 1.33, p=0.04). Although systematic biopsies are essential for detecting all csPCa, they also increase the detection of clinically insignificant (ci)PCa. An MRI-directed targeted-plus-perilesional biopsy strategy is proposed as an alternative, which limits biopsies to lesion vicinities, thus detecting nearly all csPCa while restricting ciPCa diagnoses. This emphasizes the importance of continual evaluation to ensure diagnostic accuracy and relevance.
The use of PSMA PET/CT has revolutionized staging for newly diagnosed PCa, explored further in chapters 6, 7, and 8. Chapter 6 introduces using PSMA PET/CT before biopsies to improve csPCa detection and reduce ciPCa diagnoses. Chapters 7a and 7b discuss its diagnostic value in intermediate-risk PCa, finding low incidences of PSMA-avid metastases but enabling a reduction in required scans through further subclassification. Chapter 8 addresses the variability in radiotracer interpretations, specifically highlighting increased interobserver variability with [18F]- PSMA-1007 due to nonspecific bone uptake, underscoring the importance of experience in interpretation.
Chapters 9 and 10 focus on implementing QAPs within PCa care, emphasizing their positive impact despite limited literature and consensus on their design. These chapters stress the importance of specialist motivation and clinical networks for successful QAP implementation. Chapter 10, diverging to discuss surgical management, illustrates that QAPs enhance outcomes significantly when there is active discussion among specialists, indicating their potential impact on diagnostic processes.

In summary, the thesis highlights the need for continual evaluation and improvement of diagnostic methods for PCa to reduce unnecessary diagnostics and overdiagnosis while ensuring accurate and relevant diagnostic outcomes. The findings underscore the importance of population-specific evaluations for risk calculators, the superiority of transperineal biopsies, the strategic use of MRI-directed biopsies, and the nuanced application of PSMA PET/CT in staging. Additionally, it advocates for the implementation of QAPs to improve overall PCa care outcomes.