A Phase I-II Study on the Tolerance and Efficacy of SBRT in 3 Fractions for Low/Int Risk Prostate Cancer

In the last two decades several studies have shown an exclusive sensitivity of prostate cancer cells to low doses per fraction. It has been postulated that the effect of fractionation is protective against tumor cells rather than both acute and late responding normal tissues, and this in turn tends to decrease the therapeutic index. The schedule tested here is considered biologically equivalent to deliver to the tumor, at 2 Gy per fraction, a total dose of approximately 170 Gy or more than twice of the reference schedule (76-80 Gy). On the contrary, the schedule is considered to deliver a dose of 78 Gy and 130 Gy on acute (i.e mucosa)(a/b =10 Gy) and late (a/b =3 Gy)(i.e. rectum, bladder) responding tissues.

Main selection criteria: Patients (>18 yrs/old) with low risk (primary tumor stage according to AJCC 2010: T1-2a and Gleason Score-GLS: 3+3 and serum Prostate Specific Antigen-PSA: PSA<10 ng/ml) and among those with intermediate risk features (clinical stage T2b-c or GLS 7 or PSA of 10-20 ng/ml) those with favorable ones (a single factor for intermediate risk and GLS 3 + 4 and <50% of biopsy cores containing cancer) will be selected.

Work up & pretreatment procedures: A diagnostic biopsy with at least 10 cores is needed. Patients will undergo in local anesthesia the placement both 4 fiducials (or 'gold seeds') and a gel spacer between the prostate and the rectum at least one week before the simulation. Both the seeks and the gel spacer are implanted throughout the perineum. The gel will be inserted between the posterior aspect the prostate and the anterior rectal wall to obtain a space of at least 5 mm in thickness between the two structures.

Treatment outline: Patients will be treated with EBRT, Volumetric Arc Radiotherapy on the prostate only to the total dose of 40 Gy in 3 fractions, every other day (dose per fraction=13.3 Gy). While neoadjuvant androgen deprivation is allowed for up to 3 months, no concomitant/adjuvant (to eHYPO) androgen deprivation is allowed.

Simulation & Planning: Patients will undergo both CT and MR of the pelvis for planning purposes, in the supine position.