Marieke van Son

176 CHAPTER 10 Focal therapy was introduced as a potential paradigm shift in the management of local- ized prostate cancer. The burden of overtreatment and the pursuit of function preserva- tion have generated a growing interest in this approach. While modern biopsy strategies and imaging techniques have transformed our ability to localize and characterize patho- logical lesions, there are still some uncertainties withholding the widespread adoption of focal therapy. In the primary setting, focal therapy is an organ-sparing alternative to conventional radical treatments with the primary aim of reducing treatment-related toxicity. However, it will take years before clinical evidence on its long-term oncological effectiveness becomes available. In the salvage setting, focal therapy is an opportunity for local re-treatment with the primary aim of postponing or potentially averting the need for androgen deprivation therapy (ADT). Although in this setting functional out- comes are more relevant than long-term oncological effectiveness, it remains crucial to understand which patients truly benefit from re-treatment and who should move on to watchful waiting. This thesis aimed to explore the role of focal therapy in the primary treatment setting ( part I ) and the salvage treatment setting ( part II ) and, in both settings, focused on the clinical results of MRI-guided ultrafocal HDR-brachytherapy. Besides lessons learned, there are remaining questions that will need to be addressed in future research. I. Primary treatment setting Lessons learned: • After 6 years follow-up, primary focal therapy has no clear inferiority to conven- tional whole-gland treatments in terms of need for salvage treatment, progression to metastases, need for ADT or mortality ( chapter 2 ). • Long-term cohort data and future RCT evidence are warranted to establish the posi- tion of primary focal therapy besides available whole-gland treatments ( chapter 2 ). • Ultrafocal HDR-brachytherapy has a very limited effect on urinary and bowel func- tion, but erectile dysfunction is common ( chapter 3 ). • Based on PSA progression, 4-year tumor control of ultrafocal HDR-brachytherapy seems to be poor ( chapter 3 ). For the establishment of primary focal therapy as a non-investigative, conventional treatment besides available whole-gland treatments, there are several caveats that require further investigation. Among these are the multifocal nature of prostate cancer and shortcomings in the diagnostic accuracy of localizing this multifocality(1). Ideally, focal therapy serves as the “middle ground” option for patients in whom treatment is recommended but where function preservation is highly rated. However, if cancer-free survival is diminished, the advantage of function preservation may no longer hold. A remaining challenge is the long indolent course of localized prostate cancer with pro- gression usually occurring many years after treatment. Long-term assessment (≥10 years) of oncological outcomes is needed before more definitive conclusions can be drawn about the efficacy of primary focal therapy.