Focal Micro-boost Strategy in Patients With Intermediate- to High-risk Prostate Cancer (IR-HR PCa) Undergoing Hypofractionated Radiotherapy

HYPO62 SPECIAL is a monocentric, prospective observational cohort study promoted by IFO-IRE/ISG, designed to evaluate a moderately hypofractionated radiotherapy strategy with focal micro-boost in patients with localized intermediate- or high-risk prostate cancer. Definitive radiotherapy is an established treatment option for localized prostate cancer. Over recent decades, technical advances such as 3D conformal radiotherapy, IMRT, and multiparametric MRI have enabled more precise dose delivery and better identification of dominant intraprostatic lesions. Since most local recurrences occur in the original tumor area, selective dose escalation to MRI-visible dominant lesions represents a rational strategy to improve biochemical control while limiting toxicity to surrounding organs at risk. The study is based on previous evidence, including FLAME and DELINEATE, showing that focal boosting of dominant intraprostatic lesions can improve biochemical outcomes without significantly increasing toxicity when organ-at-risk constraints are respected. At the Regina Elena National Cancer Institute, the standard moderately hypofractionated schedule consists of 62 Gy in 20 fractions to the prostate. In this protocol, visible dominant intraprostatic lesions receive a focal micro-boost up to 71.3 Gy, while seminal vesicles may receive 56 Gy according to clinical risk. The primary objective is to assess the oncological efficacy of this focal micro-boost strategy in terms of 3-year biochemical recurrence-free survival. Biochemical recurrence is defined according to the Phoenix criteria as PSA nadir plus 2 ng/mL or the start of salvage androgen deprivation therapy. Secondary and exploratory objectives include treatment-related toxicity assessed with CTCAE v5.0 at different timepoints, recurrence patterns, 3-year overall survival, and 3-year metastasis-free survival. Eligible patients are adults with histologically confirmed prostate adenocarcinoma, intermediate- or high-risk disease according to NCCN criteria, no regional or distant metastases, ECOG performance status 0-1, and at least one mpMRI-visible PI-RADS 4 or 5 lesion, or a PI-RADS 3 lesion confirmed by biopsy. All patients will provide written informed consent. Patients will be treated according to routine clinical practice with 20 fractions delivered five times per week. Treatment planning includes CT simulation and pre-treatment multiparametric MRI. The prostate, seminal vesicles when indicated, dominant lesions, and organs at risk will be contoured after CT-MRI registration. The planning target volume is generated from the clinical target volume with appropriate margins, while no additional margin is applied to the dominant intraprostatic lesion. Organ-at-risk constraints will take priority over full boost coverage. A total of 82 consecutive patients are planned for inclusion. This sample size is considered adequate to test whether the 3-year biochemical recurrence-free survival improves from 68% to 80%, with 80% probability and a one-sided 5% significance level. Statistical analyses will include Kaplan-Meier survival estimates, log-rank testing, and multivariable logistic and Cox regression models. The expected enrolment and data collection period is 36 months, with a minimum observational follow-up of 36 months and an estimated total study duration of 72 months.

Sex

Male

Minimum age

18 Years

Maximum age

99 Years

Inclusion Criteria:

* Age 18 years or older.
* Histologically confirmed diagnosis of prostate adenocarcinoma.
* Intermediate or high-risk prostate cancer according to NCCN criteria.
* No regional or distant metastases.
* ECOG performance status 0-1.
* Eligibility for moderately hypofractionated radiotherapy in 20 fractions.
* Presence of at least one PI-RADS 4 or 5 lesion on multiparametric MRI, or a PI-RADS 3 lesion confirmed as positive at pathology.
* Ability to understand the Italian language and adhere to study procedures.
* Written informed consent for participation and data processing.

Exclusion Criteria:

* Previous local prostate treatment with radiotherapy, brachytherapy, cryosurgery, high-intensity focused ultrasound or cryotherapy.
* Previous pelvic radiotherapy.
* Presence of nodal or distant metastases confirmed by MRI or PET/CT.

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