Dose-escalated radiotherapy of the dominant intraprostatic lesion: results of phase II trial

Background. One of the main methods of treating patients with prostate cancer (PCa) is radiation therapy (RT). Improvement of oncological outcomes depends on dose escalation. Thus, development of new RT techniques with increasing dose to the tumor is an urgent task.

Aim. To improve efficacy of hormone-radiation therapy in patients with PCa.

Materials and methods. In the prospective phase I–II trial, an original hypofractionated RT technique was developed based on prophylactic irradiation to the pelvic lymph nodes and prostate with 2.2 Gy to 44 Gy (45.9 iGy) and to the prostate with single dose of 2.7 Gy to total dose (TD) of 71 Gy (76.9 iGy) with simultaneous escalation of the dose to the prostate tumor to TD of 109.9 iGy. In the framework of the method, the parameters of the bladder (Bladder D2cс EQD2₃ < 90 Gy) and rectum (Rectum D2cс EQD2₃ < 75 Gy) doses described in the EMBRACE II protocol for planning RT for cervical cancer were taken as a prototype of the dose loads of the bladder.

Results. Between November 2023 and May 2024, 24 patients with PCa were treated according to the original RT method with escalation of the dose to the prostate tumor to 90/100.6/109.9 iGy, which became the criterion for dividing patients into 3 groups. At the end of RT, grade I–II gastrointestinal toxicity was observed, which completely resolved 6 months after the end of RT. Grade I–II radiation cystitis developed in more than half of the patients. Six months after the end of RT, dysuric phenomena persisted in 10 (41.6 %) patients, in 7 (29.1 %) of whom they were noted before the start of RT and were associated with the presence of the prostate tumor; in 3 (12.5 %) patients, symptoms of grade I radiation cystitis were observed. Most patients with stage T3 PCa were prescribed TD of up to 109.9 iGy. Dosimetry plans for all patients with TDs up to 90 and 100.6 iGy were optimal. However, in 2 of 8 patients with TD up to 109.9 iGy, the dose loads on the bladder (Bladder D2cc EQD2₃) were exceeded due to tumor invasion into the seminal vesicle according to stage T3b PCa. The dosimetry plan for 1 patient also with stage T3b PCa and escalation to 109.9 iGy matched all dose restrictions for the bladder, which was associated with the small size of the tumor and its location in the area of the orifice of the seminal vesicle, in contrast to the two above-described cases where the tumor invaded the seminal vesicle.

Conclusion. Dose escalation to the intraprostatic lesions can potentially improve oncological outcomes. However, its use in patients with clinical stage T3b PCa is limited due to the effect of the size and location of the prostate tumor of this stage on the dose loads for healthy organs. The option of treatment intensification in this case should be considered within the framework of personalized approach.