Erectile Dysfunction After Radiotherapy for Prostate Cancer

A Model Assessing the Conflicting Literature on Dose-Volume Effects

E Rivin del Campo; K Thomas; V Weinberg; M Roach III

Disclosures

Int J Impot Res. 2013;25(5):161-165. 

In This Article

Abstract and Introduction

Abstract

Studies assessing the relationship between dose to the penile bulb (PB) and risk of ED in men treated for prostate cancer with external beam radiation therapy (EBRT) have been critically scored. A review of published literature examining dose received by the PB and clinical erectile function outcomes for patients receiving EBRT was performed. Of 146 retrieved articles, 8 evaluated EBRT-induced ED in relation to PB dose. Half of these articles showed a relationship between dose to PB and ED, and the other half did not. A reliability score (RS) was constructed to more uniformly evaluate strengths and weaknesses of these eight articles. Subsequently, they were scored by two independent reviewers. An average of both scores was calculated. A close consensus was found (identical RS for six of the eight studies; kappa statistic: P=0.97). The studies with highest RS consistently support a relationship between ED and PB doses, whereas those with low scores did not. The RS-based analysis supports the recommended dose–volume limits specified in the Quantitative Analysis of Normal Tissue Effects in the Clinic review, maintaining the mean dose to 95% of the PB <50 Gy, although the target organ at risk is not likely to be the PB.

Introduction

Prostate cancer (PC) is among the most prevalent cancers that affect men in Western countries, only surpassed by skin cancer.[1] ED is a frequent side effect of PC treatments that significantly affects quality of life. External beam radiation therapy (EBRT) is favored over other treatment modalities because of its lower risk of impotence, as supported by the Robinson et al.[2,3] meta-analysis.

Although the risks of post-radiotherapy ED are well documented, the etiology remains unclear. In normal anatomy, functioning cavernous nerves administer nitric oxide to the penis, resulting in arterial inflow through the internal or accessory pudendal arteries and healthy erectile tissue. This ensures trapping of blood in the penis (venocclusive mechanism) and the achievement of penile erection.[4,5]

As virtually all radiation-induced complications are dose and volume dependent, efforts have been made to determine the nature of the dose–volume relationships for radiation-induced ED in men treated for PC. If a dose–volume response relationship for radiation-induced ED could be identified, it might then be possible for radiotherapy techniques to be optimized to minimize the risk of ED. Unfortunately, there are many differing opinions in the literature for the etiology of radiation-induced ED and the dose–volume effects on penile structures. The Quantitative Analysis of Normal Tissue Effects in the Clinic review performed by Roach et al.[6] addresses the challenges encountered when studying this dose–volume effect, such as the age of the patients, comorbidities and the questionnaires used to evaluate ED.

It is acknowledged that the penile bulb (PB) is not a critical component of the erectile apparatus, but based on several studies it appears that it may be a surrogate for undetermined structures that are critical components of erectile function. Empirical data support this hypothesis. It may be an ideal surrogate because of its proximity to the prostate, as well as the vascular and nerve supply and the high dose portion of the therapy, and it is also easily definable by CT. In addition, animal model studies conducted at the University of California San Francisco and elsewhere demonstrated a PB dose-related response.[7,8]

The purpose of our analysis is to assess the published literature in this area. To this end, a reliability score (RS) was constructed, based on the RS concept used in the Roach and Alexander[9] and Bach et al.[10] papers. This score will be used to evaluate the reliability of each article published on this subject in patients treated with EBRT. Although the findings may also be relevant to patients undergoing brachytherapy, we have chosen to focus this review only on EBRT because of the differences in dose rates, volumes and techniques between these two approaches and the potential impact of the traumatic nature of brachytherapy.

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