Radiation-induced erectile dysfunction: Recent advances and future directions

Abstract

Prostate cancer is one of the most prevalent cancers and the second leading cause of cancer-related deaths in men in the United States. A large number of patients undergo radiation therapy (RT) as a standard care of treatment; however, RT causes erectile dysfunction (radiation-induced erectile dysfunction; RiED) because of late side effects after RT that significantly affects quality of life of prostate cancer patients. Within 5 years of RT, approximately 50% of patients could develop RiED. Based on the past and current research findings and number of publications from our group, the precise mechanism of RiED is under exploration in detail. Recent investigations have shown prostate RT induces significant morphologic arterial damage with aberrant alterations in internal pudendal arterial tone. Prostatic RT also reduces motor function in the cavernous nerve which may attribute to axonal degeneration may contributing to RiED. Furthermore, the advances in radiogenomics such as radiation induced somatic mutation identification, copy number variation and genome-wide association studies has significantly facilitated identification of biomarkers that could be used to monitoring radiation-induced late toxicity and damage to the nerves; thus, genomic- and proteomic-based biomarkers could greatly improve treatment and minimize arterial tissue and nerve damage. Further, advanced technologies such as proton beam therapy that precisely target tumor and significantly reduce off-target damage to vital organs and healthy tissues. In this review, we summarize recent advances in RiED research and novel treatment modalities for RiED. We also discuss the possible molecular mechanism involved in the development of RiED in prostate cancer patients. Further, we discuss various readily available methods as well as novel strategies such as stem cell therapies, shockwave therapy, nerve grafting with tissue engineering, and nutritional supplementations might be used to mitigate or cure sexual dysfunction following radiation treatment.

Radiation-induced cystitis treated with hyperbaric oxygen therapy (RICH-ART): a randomised, controlled, phase 2–3 trial

“…Symptoms from these domains are common, and very few studies have assessed the effects of HBOT. 264,265 We are aware, however, of one study currently being performed with this focus: "Hyperbaric Oxygenation Treatment and Quality of Life," Haukeland University Hospital, Bergen, Norway. 266 This study is focusing on female patients for whom late radiation-induced injuries frequently lead to sexual dysfunction.…”

Long-Term Follow Up of the Erectile Function of Testicular Cancer Survivors

“…The side effects of several chemotherapy drugs include endothelial damage, angiopathy, and peripheral neuropathy, which may be linked to erectile and ejaculatory disorders (35, 36). Radiotherapy can cause sexual dysfunctions by inducing damage to the cavernous nerve and/or progressive fibrosis of the cavernous tissue and endothelial damage, which can become clinically evident through the onset of erectile dysfunction even several years post-treatment (37). However, the literature data are inconsistent, as several studies report no significant associations between sexual dysfunctions and specific treatment modalities (31), while others report the significant influence of either chemo- or radiotherapy (14, 15, 32, 38).…”

Older Age, Early Symptoms and Physical Function are Associated with the Severity of Late Symptom Clusters for Men Undergoing Radiotherapy for Prostate Cancer

“…Acute bladder symptoms were also a precursor of late symptoms and patients with pretreatment bladder symptoms were more likely to report bladder symptom at 5 years [62] . Emerging evidence around phosphodiesterase type 5 (PDE5) inhibitors suggests that these agents may have an impact not only on sexual but also on urinary symptoms [63] , [64] . However, the clinical mechanisms of this effect remain unclear.…”