Abstract
PurposeThe aim of this review was to compare radiation toxicity in Localized Prostate Cancer (LPC) patients who underwent conventional fractionation (CV), hypofractionated (HYPO) or extreme hypofractionated (eHYPO) radiotherapy. We analyzed the impact of technological innovation on the management of prostate cancer, attempting to make a meta-analysis of randomized trials.MethodsPubMed database has been explored for studies concerning acute and late urinary/gastrointestinal toxicity in low/intermediate risk LPC patients after receiving radiotherapy. Studies were then gathered into 5 groups: detected acute and chronic toxicity data from phase II non randomized trials were analyzed and Odds Ratio (OR) was calculated by comparing the number of patients with G0-1 toxicity and those with toxicity > G2 in the studied groups. A meta-analysis of prospective randomized trials was also carried out.ResultsThe initial search yielded 575 results, but only 32 manuscripts met all eligibility requirements: in terms of radiation-induced side effects, such as gastrointestinal and genitourinary acute and late toxicity, hypofractionated 3DCRT seemed to be more advantageous than 3DCRT with conventional fractionation as well as IMRT with conventional fractionation compared to 3DCRT with conventional fractionation; furthermore, IMRT hypofractionated technique appeared more advantageous than IMRT with conventional fractionation in late toxicities. Randomized trials meta-analysis disclosed an advantage in terms of acute gastrointestinal and late genitourinary toxicity for Hypofractionated schemes.ConclusionsAlthough our analysis pointed out a more favorable toxicity profile in terms of gastrointestinal acute side effects of conventional radiotherapy schemes compared to hypofractionated ones, prospective randomized trials are needed to better understand the real incidence of rectal and urinary toxicity in patients receiving radiotherapy for localized prostate cancer.
Highlights
In the treatment of prostate cancer, we can’t diseregard that organs at risk (OARs), as rectum or bladder, have an estimated α/β ratio of 3-5 Gy for late toxic effects and 10 Gy for acute toxicity, whereby prostate cancer cells are more responsive to a larger fraction size, with a clear therapeutic gain [9]
Further advances in radiation delivery techniques, such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), led to a greater sparing of adjacent normal tissue and consequent reduced toxicity
The initial search yielded 575 results. 363 publications were excluded, which dropped down the initial number to 212. These articles were reviewed and 54 studies, which did not evaluate both acute and chronic toxicity genitourinary GU and gastrointestinal GI, were removed. 158 full-text articles were evaluated but further 126 studies were discarded because assessing aftersurgery treatments, old techniques, retrospective studies or had few data
Summary
Prostate cancer is one of the most frequent tumors affecting men in the world: external beam radiotherapy (EBRT) is a standard treatment modality for localized and locally advanced prostate cancer [1, 2].Modern technologies, predictive biomarkers of response to a given therapy, potential new targets for biological therapy and advanced knowledge of radiobiology have changed the approach to prostate cancer radiotherapy [3,4,5].Many publications suggest that prostate cancer has a low α/β ratio (ratio between “intrinsic radiosensitivity” and “reparative capacity”), compare to healthy tissues [1,2,6] with notable therapeutic implications [6,7,8]. Prostate cancer is one of the most frequent tumors affecting men in the world: external beam radiotherapy (EBRT) is a standard treatment modality for localized and locally advanced prostate cancer [1, 2]. Predictive biomarkers of response to a given therapy, potential new targets for biological therapy and advanced knowledge of radiobiology have changed the approach to prostate cancer radiotherapy [3,4,5]. Further advances in radiation delivery techniques, such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), led to a greater sparing of adjacent normal tissue and consequent reduced toxicity. Significant reduction of margins around the prostate, and irradiated normal tissue volume, has been achieved by the use of daily cone-beam computed tomography imaging prior to each treatment delivery [15]
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