Hypo Fractionated Versus Conventional IMRT in Unfavorable Intermediate- and High-Risk Prostate Cancer

Hypo Fractionated Versus Conventional IMRT in Unfavorable Intermediate- and High-Risk Prostate Cancer: A Phase II Comparative Study of PSA Kinetics and Dosimetric Outcomes

The aim of the study is

1. Statistical evaluation of patients' characteristics who have intermediate & high risk localized prostate cancer.
2. Statistical analysis of treatment efficacy of combined hormonal therapy & hypo fractionated intensity modulated radiotherapy compared with conventionally fractionated radiotherapy plus hormonal treatment as regard biochemical failure, disease free survival & overall survival.
3. Evaluation of acute as well as late toxic side effects after radiotherapy.

The incidence rate of prostate cancer is rapidly increasing, and it has become the most prevalent solid tumor diagnosed in men.

In most cases the prostate cancer is organ-confined at the time of initial diagnosis . Radical prostatectomy and radiotherapy, either given as a seed implant or external beam radiation therapy, are the accepted standard options for treating the primary tumor itself, and androgen deprivation may be added selectively for certain cases with an intermediate or high risk of dissemination based on clinical and pathologic features evident at the time of diagnosis.

Regarding the specific option of external beam radiotherapy, the current widely accepted standard regimen for organ-confined prostate cancer involves approximately eight weeks of fractionated treatments with a daily dose of 1.8-2.0 Gy to a total dose in the range of 70-80 Gy .

Over the last decade, there have been three major advances in the use of external RT for the management of clinically localized prostate cancer: (a) androgen deprivation therapy ; (b) image-guided ration therapy with three-dimensional conformal radiotherapy and intensity modulated radiotherapy , and particularly c) radiation dose escalation schedules compared with conventional 70-80 Gy (2 Gy per fraction), which has been shown to improve biochemical and distant metastases control with minimum toxicity, but not overall survival .

The rapid dose gradients, which are able to be generated with Intensity Modulated Radiation Therapy have been demonstrated to reduce OAR dose relative to three-dimensional conformal radiotherapy resulting in well-established reductions in toxicity in the conventionally fractionated, dose escalated prostate cancer radiotherapy setting .

The use of conventional fractionated radiation therapy with a single 1.8-2 Gy fraction/day is related to more radiation therapy sessions and longer treatments; therefore, influencing the decision-making and patient non-adherence, since longer treatments can affect their financial situation (by not being able to work during radiotherapy) or cause a disruption in their daily life .

Hypofractionated Radiation Therapy and conventional fractionated radiation therapy schedules have been shown to be isoeffective in terms of incidence of biochemical control or late complications in several phase III trials .

The aim of the study is

1. Statistical evaluation of patients' characteristics who have intermediate & high risk localized prostate cancer.
2. Statistical analysis of treatment efficacy of combined hormonal therapy & hypo fractionated intensity modulated radiotherapy compared with conventionally fractionated radiotherapy plus hormonal treatment as regard biochemical failure, disease free survival & overall survival.
3. Evaluation of acute as well as late toxic side effects after radiotherapy.

Inclusion Criteria:

• Biopsy proven prostate adenocarcinoma
• Patient has been classified as intermediate or high risk according to the National Comprehensive Cancer Network v2018 .
• Clinically localized stage (cT2-T3b N0M0, using the AJCC 8th TNM classification) .
• Eastern Cooperative Oncology Group performance status ranged from 0-1 . - Mean age was 65 years (range: 50-80 years).
• a prostate-specific antigen test at the time of diagnosis ≥10 ng/ml.
• Gleason scores range from 7 to 10.
• The patient must not receive any cytotoxic anticancer therapy for prostate cancer prior to randomization.
• Adequate hematological, hepatic, renal function tests

Exclusion Criteria:

• Patients with a history of other malignancies, except: non-melanoma skin cancer.
• Patients with any contraindication to pelvic radiotherapy: including, previous pelvic radiotherapy, inflammatory bowel disease or severe bladder irritability.
• Patients who had prior surgical treatment for carcinoma of the prostate apart from trans-urethral resection,
• Nodal or distant metastasis proven by a computed tomography pelvis or bone scan,
• Co-morbidities as Congestive heart failure, recent myocardial infarction.