Discussion
toxicity, Lu-PSMA in hormone naïve prostate cancer, prostate, tumour, primary node-positive prostate cancer
METASTASIS, TUMOUR, INCURABLE DISEASE, PROSTATE
Current treatment (EBRT and ADT) for patients diagnosed with primary node-positive prostate cancer without distant metastasis comes with significant toxicity and reductions in QoL, while still being confronted with recurrent and incurable disease within their remaining life. In the current study, the tolerability of innovative combined modality treatment strategy will be explored (standard of care; EBRT of the prostate and regional pelvic nodes combined with 2–3 years ADT) complemented with systemic [The risk of significant extra toxicity due to the addition of one cycle of [The PSMA-positive primary tumour in the prostate may receive very high combined doses from EBRT with [The total dose delivered to tumour deposits in regional involved nodes is higher than any preceding study, up to 88 Gy EQD2 for macroscopic metastasis in the highest activity level. However, due to the sharp drop-off in the dose from [The toxicity of ADT is considered to be largely independent of ionizing radiation, and is not expected to change in the scope of combining EBRT with [The combination of locoregional EBRT and systemic radioligand therapy is not new [The benefit of combining EBRT with [Since the expected anti-tumour effect of combining multiple treatments that each have individual proven anti-tumour effect is high, and the combined toxicity of these treatments is expected to be limited, it is likely that this study will result in successful dose-finding with confirmed tolerability and improved dosimetric efficacy. Subsequent studies will prove the future potential benefit of concurrent EBRT with [Potential further improvements to the treatment strategy may be identified in due time. Anticipated options include: First, intra-arterial administration of [There are other groups that could benefit from similar treatment intensification with [Currently, there are three other studies registered that are also investigating Lu-PSMA in hormone naïve prostate cancer patients. Firsty, PSMAddition (NCT04720157), an international, multicenter, open-label, randomized, phase III study investigating [This study protocol has some limitations: Firstly, the BOIN-design is chosen for more flexibility in: the chosen target toxicity rate and cohort size and has a better performance in comparison to 3 + 3 design [Secondly, the choice to start with three GBq was based on earlier safety and efficacy studies, where they used a administered activity of six GBq [