Marieke van Son

183 GENERAL DISCUSSION AND FUTURE PERSPECTIVES Future perspectives For the future, the role of focal therapy among whole-gland treatment options will in part depend on the extent to which innovations can further reduce whole-gland treat- ment-related side effects. In the early 1990s, physicians became more aware of morbid- ity related to whole-gland prostate cancer treatments. The general view was that with refinements of surgical techniques and radiation advancements, erectile dysfunction and incontinence could be largely reduced(45, 46). Indeed, some improvements have already contributed to reducing complication rates. For radical prostatectomy, these include nerve-sparing techniques, centralization in high ‐ volume expert centers and (although controversial) robot-assisted surgery(47-49). Although a recent review showed that 82% of patients still reported erectile dysfunc- tion after bilateral nerve-sparing surgery (versus 95% after conventional surgery)(50), the NeuroSAFE technique has now been introduced as an approach to further im- prove erectile function preservation(51). With this technique, the prostate is removed with bilateral nerve ‐ sparing after which a frozen-section examination is performed to decide whether a secondary resection of the neurovascular bundle is necessary. A cohort-based analysis of 258 patients undergoing NeuroSAFE prostatectomy showed that 25% had positive surgical margins prompting a secondary neurovascular bundle resection. However, in 72% of bundle resections, no tumor was present. The authors concluded that the neurovascular bundle can be spared in the majority of patients and that secondary nerve bundle resection might even be omitted in patients with small positive surgical margins of ≤1 mm with Gleason pattern 3, supporting individual in- traoperative clinical decision ‐ making(52). However, such decisions should be made with caution, as the entire approach relies on meticulous pathological examination. If the pathologist misses significant cancer (due to inadequate slice thickness or mi- croscopic inspection), this may compromise the oncological safety of the procedure. Unfortunately, it will take years before long ‐ term oncological outcome data will become available. A future trial planning to randomize between NeuroSAFE prostatectomy and nerve-sparing as per standard of care will aim to investigate both functional outcomes and cancer control(53). In the field of primary whole-gland radiotherapy, dose escalation without increasing toxicity has become more achievable since the introduction of volumetric arc external beam radiotherapy (VMAT) and intensity-modulated radiation therapy (IMRT) tech- niques(54). Although most trials have not been able to show a significant prostate cancer-specific or overall survival advantage for patients treated with ≥74 Gy, dose escalation at least seems to reduce the need for secondary therapies(55, 56) and it is now an accepted standard of care with low rates of severe side effects(57). The low estimated α/β ratio of prostate cancer translates into a potential benefit from hy- pofractionation, with encouraging results from studies investigating external beam radiotherapy in only 4-5 fractions(58, 59). The introduction of the MR-Linac, in which a linear accelerator is integrated with a diagnostic quality MRI-scanner, has made it possible to adapt the radiotherapy plan to anatomic changes during treatment and 10