Postop Hypofractionated Radiation Therapy and LHRH in Patients With Prostate Cancer
Postop Hypofractionated Radiation Therapy and LHRH in Patients With Prostate Cancer
Prostate cancer is the second most common cancer among Canadian men of which approximately
 20-30% present with high-risk tumour characteristic.

 Although surgery can be curative in patients evidencing pathological high-risk disease
 (extracapsular extension, seminal vesicle involvement, positive surgical margins), a large
 proportion will develop biochemical failure within years from the surgical procedure. The
 failure rate is even more pronounced in those patients that present with high prostate
 specific antigen (PSA) levels, pT3 disease, positive margins and Gleason score ≥8 with an
 estimated 75% failure rate at 10 years.

 Post-operative radiotherapy (RT) has been shown in three randomized trials to significantly
 decrease the biochemical failure rate and in one of the trials a survival benefit was also
 seen with the addition of post-operative RT and is considered by many investigators standard
 therapy in patients with pathological high-risks factors even in absence of biochemical
 failure.
Although RT is known to potentially eradicate microscopic disease localized in the prostatic
 bed, the current dilemma is whether to deliver RT in the adjuvant setting (defined as the use
 of RT post-prostatectomy to patients at a higher risk of recurrence because of adverse
 pathological features prior to evidence of disease recurrence (i.e., with an undetectable
 PSA) or to use it as an early salvage therapy (defined as the use of RT in patients with
 rising PSA but no evidence of metastatic disease).

 There are several institutional retrospective reports on the use of RT as salvage therapy but
 no randomized trial has ever been completed. The best evidence available, however, supports
 early salvage RT as the best strategy to be used to maximize results.

 Our own group has shown excellent results using this approach in patients with low and
 intermediate risk disease and is currently exploring this approach in patients with high-risk
 disease. Hypofractionated RT offers a more convenient shorter course of treatment, reduces
 health-costs and appears to be as effective and safe as conventionally fractionated regimens.

 This Phase 2 trial will study the potential role of hypofractionated in the post-operative
 setting in patients with high-risk features with the primary objective of assessing toxicity
 from this approach.

 The use of androgen deprivation therapy in combination with RT in the primary treatment for
 patients with intermediate or high-risk prostate cancer is well established. The use of
 androgen suppression in the post-operative setting has been less explored and its definitive
 role has not been fully explored.

 This is a phase II clinical trial to assess the feasibility and overall toxicity of adding
 one injection of neo-adjuvant hormonal therapy starting 12 weeks before plus Hypofractionated
 Radiotherapy for four weeks concurrently with another injection of luteinizing
 hormone-releasing hormone (LHRH) analog in patients with post-operative setting in patients
 with high-risk features.
Inclusion Criteria:

 -  Histologically proven high risk (any of the following risk factors: surgical positive
 margins; extra-capsular extension; seminal vesicle involvement, Gleason score >7)
 adenocarcinoma of the prostate after a radical prostatectomy as primary treatment
 (adjuvant group), with pathologically negative lymph nodes dissection or clinically
 negative lymph nodes by imaging [pelvic and abdominal computed tomography (CT) scan,
 or magnetic resonance imaging (MRI)]. Lymphadenectomy is not mandatory. Any type of
 prostatectomy will be permitted. For this group of patients, the PSA level at time of
 entry must be below 0.4 ng/ml

 -  Histologically proven adenocarcinoma after a radical prostatectomy with pathologically
 negative lymph nodes (lymphadenectomy is not mandatory) or clinically negative lymph
 nodes by imaging (pelvic and abdominal CT scan, or MRI or) and evidence of biochemical
 failure (defined as two consecutives rises of the PSA, at any PSA level). PSA upper
 limit post-prostatectomy must be below 2.0 ng/ml (salvage group). Any type of
 prostatectomy will be permitted

 -  Negative bone metastases proven by bone scan. The use of proton emission tomography
 (PET) fluoride is allowed

 -  History and physical examination (including digital rectal exam) within 90 days prior
 of registration

 -  Adequate marrow reserve defined as: Hemoglobin ≥ 10 g/dl (patients may be transfused
 in order to achieve this level); Platelets ≥ 100 000 cells/mm3 and a white blood cell
 count of ≥ 4000 cells/ml3

 -  AST or ALT <2 x the upper limit of normal

 -  PSA and testosterone levels within one month of registration Age ≥ 18

 -  Zubrod Performance Status 0-1

 -  Patients must sign a study-specific consent form

 Exclusion Criteria:

 -  Previous exposure to androgen deprivation

 -  Chemotherapy before or after prostatectomy

 -  Prior pelvic radiotherapy

 -  Previous malignancies (except non-melanomatous skin cancer) unless disease-free >5
 years

 -  Severe, active medical condition that makes the use of any of the therapies of the
 study not recommended