Understanding Urinary Toxicity after Radiotherapy for Prostate Cancer: First Steps Forward

Abstract

Tumori 2017; 103(5): [395][396][397][398][399][400][401][402][403][404] REVIEW -BONADONNA LECTURE SERIES may be differently related to the absorbed dose. For example, rectal bleeding arises as a serial effect and is mainly related to the absorption of high doses in small rectal mucosa volumes, whilst fecal incontinence is related to intermediate doses absorbed by large rectal volumes.The development of reliable models of radiation-induced toxicities along with the available level of technology has determined an efficient improvement of the treatment plans, even in dose-escalated or hypofractionated regimens. This is particularly true for moderate and severe rectal toxicities, which had an incidence close to 20% in the 1990s while in the most recent publications they have fallen below 7%-10%.However, an analogous result has not yet been reached in urinary symptoms. This is mainly due to the difficulty in sparing the bladder, which is partially but unavoidably included in the target volume, as well as to the clear lack of knowledge concerning the predictors of urinary toxicity. The main reason for this deficiency is probably the difficulty in following for a sufficiently long time a large number of patients whose clinical and dosimetry data need to be individually and prospectively collected with proper evaluation of urinary symptoms. Some important symptoms (e.g., incontinence) may indeed continuously arise after radiation therapy and their incidence reaches a plateau only many years (typically 5-8) after treatment. The fulfilment of reliable models of radiation-induced urinary sequelae is therefore made particularly challenging by the complexity of symptoms, their evolution over time, and the strong dependence on the baseline situation.It is widely acknowledged that radiation-induced toxicity is a multifactorial problem, depending not only on the delivered

Pre-clinical Research on Bladder Toxicity After Radiotherapy for Pelvic Cancers: State-of-the Art and Challenges

“…Here, imageguided radiotherapy (IMRT) reduced bladder areas overlaying the planning target volume (PTV) and hence lowered urinary toxicity risk. A spatial effect was also highlighted in the trigone, the most radiosensitive bladder substructure, for which the mean dose delivered was proven to be strongly associated to a higher risk of severe acute and late urinary damage (19). More recently, growing evidence of bladder sensitivity to fractionation suggested an α β value (a parameter of the sensitivity of both tumor and healthy tissues to fractionation) significantly lower than previously hypothesized, in the range of 1 Gy.…”

“…In particular, several recent reviews (17)(18)(19)(20) have outlined how radiation dose correlates to the risk of urinary toxicity. Evidence of a quite rapid increase of the risk of Grade 3 urinary toxicity according to the Common Toxicity Criteria for Adverse Events (CTCAE, e.g., urethral stenosis and/or bladder neck stricture requiring surgical intervention, gross hematuria requiring blood transfusion and/or hyperbaric oxygen therapy, urinary incontinence requiring treatments such as invasive treatment) (21) for 2-Gy equivalent doses (EQD2) to the whole bladder above 50-55 Gy have been demonstrated (22).…”

“…Another significant issue concerns evidence of "spatial" effects suggesting that specific sub-structures (i.e., the trigone) may be more sensitive to radiation (18)(19)(20): experiments set to identify the mechanisms underlying these effects would be of paramount importance in guiding plan optimization to selectively reduce the dose to these sub-structures.…”

A New Approach for Quantifying Radio-Biological Effects Using the Time Course of Mouse Leg Contracture

“…Late effects of radiation, which can occur several months after radiation therapy, are a frequent problem in clinical radiation protocols. [20][21][22] No standard method to estimate late effects of radiation at clinical doses has been established. An estimation of radio-biological effects based on the 30-d survival rate of mice may be not suitable for estimating late effects of radiation.…”

Predictors of 2-Year Incidence of Patient-Reported Urinary Incontinence After Post-prostatectomy Radiotherapy: Evidence of Dose and Fractionation Effects

“…Urinary toxicity is a common side effect of radiotherapy for prostate cancer (PCa), despite the modern intensity-modulated (IMRT) delivery techniques and image-guidance technologies currently available (1,2). Amongst the wide variety of symptoms included in the term "urinary toxicity, " urinary incontinence (UI) plays an important role in the deterioration of patient quality of life.…”