Discussion
prostate nerve bundle, tumor, mpMRI-US-fused prostate
TUMOR, RECURRENCE, DISEASE, METASTATIC DISEASE, REGRESSION, DISEASE PROGRESSION
In our prospective, single-center clinical study of HIFU treatment in unilateral localized PCa we demonstrate high progression rates with overall FFS of only 62%. Despite lower AE compared to RP and RT we had to stop HIFU treatment in localized unilateral PCa because of oncologic safety concerns.HIFU treatment is based on index lesion theory which has not been properly confirmed, yet. As long as several large pathological analyses of patients undergoing RP reveal multifocal disease in up to 80%, we have to address this knowledge to our patients treated by FT [Moreover, high accuracy in optimal patient selection is extremely important for any FT to detect focal disease based on index lesion theory, which is primarily based on mpMRI-US fusion biopsyDespite our efforts in maximal accurate patient selection to address the underlying index theory of FT, we report an unexpected high number of tumor regression with median FFS rate of approximately 62% of total study cohort (median time until study drop-out of 22 months). Most importantly, one patient developed metastatic disease leading to palliative care. Comparing our results with those of other centers, only few midterm follow-up results are published reporting significant treatment failure and need for re-treatment. One of the largest cohorts has been published in 2019 with a total of 1032 men treated with HIFU between 2005 and 2017 with median follow-up of 36 months [Notably, we did not include second HIFU treatment in our study protocol because it prevents causal relationships of cause and effect. Second, we regard high rates of re-treatment by 70% as a critical issue that needs to be discussed, especially when 5-year progression-free survival rates for RP above 80% are documented in large prospective trials [Regarding further smaller study cohorts, PCa recurrence and progression rates after FT treatment also varied from 20 to 30% [Ultimately, our results strengthen the need to increase diagnostic accuracy to detect localized PCa. This could be achieved by further narrowing the inclusion criteria in terms of more localized, small-volume PCa. We propose to establish HIFU study protocols including PSMA PET-CT. Based on the phase III “proPSMA” trial, there is strong evidence for significant improvement in identifying pelvic nodal and distant metastatic PCa compared to conventional CT and bone scanning [Nevertheless, we can confirm overall low rates of AE as compared RP or RT [Additionally, we need to address AS treatment for patients with low-risk PCa. Compared to definitive treatment or focal HIFU, AS does not have Clavien ≥ 3 AEs and provides high evidence-based long-term follow-up data showing comparable overall survival in appropriately selected patients. Disease progression rates of AS leading to definitive treatment might also be high, up to approximately 60% in long-term follow-up of 10 years and median FFS up to 8.5 years [Finally, we encourage technical improvements of FT to further increase the effectiveness of ablative technologies to achieve even better local destruction of PCa cells, while better protecting the surrounding tissue, including prostate nerve bundle preservation. Moreover, the usage of HIFU is limited in treatment of prostates larger than 40 ccm or to lesions within 4 cm from the treatment site [We are aware of the limitations of our study, in particular the limited sample size. However, we had to stop the trial after treating 29 patients based on our trial protocol. Thus, we are not able to perform an in-depth multiple logistic regression analysis to identify, for example, risk factors for failure after HIFU treatment. To further evaluate these factors, we would need at least 40–50 patients per parameter. Furthermore, mpMRI-US-fused prostate biopsies were conducted by several urologists and MRI was analyzed by different radiologists, thereby interobserver bias is of specific relevance. Nevertheless, our results resemble real world experience which we believe is very important for colleagues in urology and their daily treatment recommendations.