Radiotherapy for prostate cancer and sexual health

Sexual dysfunction is very common after treatment of prostate cancer. Radiation therapy together with radical prostatectomy is the most effective treatment for localized disease. Percentages of erectile dysfunction (ED) reported in prospective studies after external-beam radiotherapy (RT) vary from 60-70%, and these are similar after brachytherapy. In randomized trials more realistic percentages of 30-40% are reported. Modern techniques do not seem to decrease post-radiation ED. No final conclusions can be drawn whether or not the radiation dose to the penile structures correlates with post-radiation ED in patients treated for prostate cancer. The etiology of ED after RT of prostate cancer is most probably multi-factorial. The phosphodiesterase type 5 inhibitors (PDE5-I) sildenafil and tadalafil have been shown to be effective to treat post-radiation ED in about half of the patients in randomized trials. Patients and their partners need to be adequately counselled on the effects of cancer treatment on their sexual life and relationship, and about the different treatment possibilities. Sexual counselling has not become yet a routine part of oncology care in most hospitals, but this should be provided. Due to the lack of robust data, prevention of post-radiation ED with PDE5-I cannot be recommended so far.     

Surgery and hormonal treatment for prostate cancer and sexual function

Prostate cancer (PC) is one of the most common cancers effecting men today. With earlier detection and improvements in available treatment modalities, there still remains significant morbidity associated with the treatment of PC. Male sexual health and erectile function are greatly impacted by these therapies and remain a concern to PC survivors. This article reviews the current literature on male sexual health following radical prostatectomy (RP) or androgen ablation therapy for PC. Each treatment modality affects male sexual function to an appreciable level, although certain patients have better outcomes if they have preoperative potency, are younger, or have nerve-sparing surgery. There is a delayed recovery up to 2 years seen in erectile function following RP. With androgen deprivation therapy (ADT), attempts can be made at different administration strategies and exercise may possibly play a role in maintaining erectile function. Penile rehabilitation protocols attempt to protect erectile function immediately following therapy through different modalities, although no one approach has been agreed upon.     

Penile rehabilitation following prostate cancer treatment: review of current literature

Radical prostatectomy (RP) and radiotherapy (RT) are highly effective in improving prostate cancer survival. However, both have a detrimental effect on erectile function (EF). Penile rehabilitation consists of understanding the mechanisms that cause erectile dysfunction (ED) and utilizing pharmacologic agents, devices or interventions to promote male sexual function. For the past decade, many researchers have pursued to define effective treatment modalities to improve ED after prostate cancer treatment. Despite the understanding of the mechanisms and well-established rationale for postprostate treatment penile rehabilitation, there is still no consensus regarding effective rehabilitation programs. This article reviews a contemporary series of trials that assess penile rehabilitation and explore treatment modalities that might play a role in the future. Published data and trials related to penile rehabilitation after RP and RT were reviewed and presented. Although recent trials have shown that most therapies are well-tolerated and aid in some degree on EF recovery, we currently do not have tangible evidence to recommend an irrefutable penile rehabilitation algorithm. However, advancements in research and technology will ultimately create and refine management options for penile rehabilitation.     

Psychosexual care in prostate cancer survivorship: a systematic review

Background

Prostate cancer (PC) is the most common cancer in men. Due to improvements in medical care, the number of PC survivors is increasing. Current literature demonstrates survivors have significant unmet needs including psychosexual care. We assess patients psychosexual needs by systematic review of literature over the past 20 years up to May 2015 in order to see what issues need to be addressed within psychosexual care.

Methods

A systematic review was conducted on PC survivorship and psychosexual care. The search strategy aimed to identify all references related to PC survivorship programme components (parts of survivorship programmes) AND survivorship AND psychosexual concerns. Search terms used were as follows: (PC OR prostate neoplasms) AND (survivorship OR survivor*) OR [psychosexual impairment or sexual dysfunction or erectile dysfunction (ED)] AND [comorbidity or quality of life (QoL)].

Results

The systematic review identified 17 papers, examining unmet needs in psychosexual care post PC therapy.

Conclusions

These findings of this review may change psychosexual care of PC survivors, as national and international guidance is needed.     

Generating comprehensive comparative evidence on various interventions for penile rehabilitation in patients with erectile dysfunction after radical prostatectomy: a systematic review and network meta-analysis

BackgroundWe aim to present a comprehensive comparison of various treatments in the management of penile recovery after radical prostatectomy (RP) and provide recommendations for future research.MethodsLiterature search of electronic databases including PubMed, the Cochrane Library, Embase, PsycInfo, and Web of Science, and manual retrieval were conducted from inception through March 2020. “Erectile dysfunction” and “prostatectomy” were used as the Mesh terms. The patients, intervention, comparison, outcome, and study design (PICOS) approach were used to define study eligibility. Two authors independently selected studies, evaluated the methodological quality, and extracted data using Cochrane Collaboration’s tools. The data analysis was completed by STATA version 14.2.ResultsA total of 24 studies with 3,500 patients were incorporated in the final analysis after screening 6,131 records. Our findings indicated that vacuum constriction devices (VCD) ranked 1st which meant that patients in VCD group had the best effect regarding mean IIEF scores within 3 months after RP, and no significant difference was observed between VCD and VCD with 20 mg/day tadalafil (V20DT) (MD: 5.44; 95% CI: −0.81 to 11.69). VCD and 50 mg/day sildenafil (VC50DS) showed superiority over 50 mg/day sildenafil (50DS) (MD: 3.75; 95% CI: 2.74–4.76) and intraurethral alprostadil 125–250 µg (MD: 3.05; 95% CI: 0.38 to 5.72), respectively. Moreover, V20DT showed significant superiority over the other interventions for ≥6 months mean International Index Erectile of Function (IIEF) scores after RP. Monotherapy appeared to have similar efficacy in terms of mean IIEF scores and proportion of patients return to baseline, and the effect of phosphodiesterase type 5 inhibitors (PDE5is) did not seem to be affected by the patterns of administration (regular or on demand).ConclusionsThe combination therapy showed certain advantages over monotherapy, and we recommended the combination of VCD and PDE5is to be considered in the clinical management of penile rehabilitation after RP.     

Sexual dysfunction due to pudendal neuralgia: a systematic review

BackgroundThe pudendal nerve is considered as the main nerve of sexuality. Pudendal neuralgia is an underdiagnosed disease in clinical practice. The aim of this systematic review is to highlight the role of pudendal neuralgia on sexual dysfunction in both sexes.MethodsA PubMed search was performed using the following keywords: “Pudendal” AND “Sexual dysfunction” or “Erectile dysfunction” or “Ejaculation” or “Persistent sexual arousal” or “Dyspareunia” or “Vulvodynia”. The search involved patients having sexual dysfunction due to pudendal neuralgia. Treatment received was also reported.ResultsFive case series, seven cohort studies, two pilot studies, and three randomized clinical trials were included in this systematic review. Pudendal nerve and/or artery entrapment, or pudendal neuralgia, is a reversible cause of multiple sexual dysfunctions. Interventions such as anesthetic injections, neurolysis, and decompression are reported as potential treatment modalities. There are no studies describing the role of pudendal canal syndrome in the pathophysiology or treatment of delayed ejaculation or penile shortening.DiscussionPudendal neuralgia is an underestimated yet important cause of persistent genital arousal, erectile dysfunction (ED), premature ejaculation (PE), ejaculation pain, and vulvodynia. Physicians should be aware of this entity and examine the pudendal canal in such patients before concluding an idiopathic cause of sexual dysfunction.     

Sexual function after anterior urethroplasty: a systematic review

BackgroundUrethral surgery outcomes are often evaluated by assessing urinary flow and urethral patency. However, sexual consequences may appear after urethroplasty, impairing quality of life and patient’s perception of success.The aim of this study is to assess the relationship between anterior urethral reconstruction and postoperative sexual dysfunction, including the proposed factors predicting sexual outcomes.MethodsWe searched in PubMed database using the terms: “anterior urethroplasty”, bulbar urethroplasty” or “penile urethroplasty”, and “sexual dysfunction”, “erectile function” or “ejaculation”. Articles were independently evaluated for inclusion based on predetermined criteria. Systematic data extraction was followed by a comprehensive summary of evidence.ResultsThirty-eight studies were included for final analysis. No randomised trial on the topic was found. Urethral surgery might affect different aspects of sexual function: erectile function, ejaculatory function, penile shape and length, and genital sensitivity, leading to severe sexual dysfunction. Patient perception of sexual impairment was related to post-operative satisfaction.ConclusionsSexual dysfunction after anterior urethral reconstruction is an important issue that must be appropriately discussed during preoperative patient counselling. Reported outcomes after anterior urethroplasty should include sexual consequences and relevance, evaluated using validated tools.     

Erectile dysfunction following treatment of prostate cancer: new insights and therapeutic options

Prostate cancer remains the most common cancer in adult men. Its treatment usually results in compromised or absent erectile function. This article will review the treatment options available to resume sexual activity following prostate cancer therapy and will focus on non-surgical treatment options. In addition, intracavernosal injection therapy has been shown to enhance recovery of spontaneous, unassisted erections when started shortly after nerve-sparing radical prostatectomy. Most recently, oral treatment with sildenafil citrate begun shortly after surgery was shown in a placebo-controlled trial to encourage return of normal erections. Presumably this occurs by promoting nocturnal erections which appear to prevent the permanent neurovascular damage to the penis following radical prostate surgery.     

Prevention and management of post prostatectomy erectile dysfunction

Sexual dysfunction is common in patients with prostate cancer (PC) following radical prostatectomy (RP). Review the available literature concerning prevention and management strategies for post-RP erectile function (EF) impairment in terms of preoperative patient characteristics, intra and postoperative factors that may influence EF recovery, and postoperative treatments for erectile dysfunction (ED). A literature search was performed using Google and PubMed database for English-language original and review articles, either published or e-published up to July 2013. The literature still demonstrates a great inconsistency in the definition of what is considered normal EF both before and after RP. Thus, using validated psychometric instruments with recognized cut-offs for normalcy and severity during the pre- and post-operative evaluation should be routinely considered. Therefore, a comprehensive discussion with the patient about the true prevalence of postoperative ED, the concept of spontaneous or pharmacologically-assisted erections, and the difference between “back to baseline” EF and “erections adequate enough to have successful intercourse” clearly emerge as key issues in the eventual understanding of post-RP ED prevention and promotion of satisfactory EF recovery. Patient factors (including age, baseline EF, comorbid conditions status), cancer selection (non- vs. uni- vs. bilateral nerve-sparing), type of surgery (i.e., intra vs. inter vs. extrafascial surgeries), surgical techniques (i.e., open, laparoscopic and robotically-assisted RP), and surgeon factors (i.e., surgical volume and surgical skill) represent the key significant contributors to EF recovery. A number of preclinical and clinical data show that rehabilitation and treatment in due time are undoubtedly better than leaving the erectile tissue to its unassisted postoperative fate. The role of postoperative ED treatment for those patients who received a non-nerve-sparing RP was also extensively discussed. Optimal outcomes are achieved mainly by the careful choice of the correct patient for the correct type of surgery. Despite a plethora of potential rehabilitative approaches, they should be only considered as “strategies”, since incontrovertible evidence of their effectiveness for improving natural EF recovery is limited. Conversely, numerous effective therapeutic options are available for treating post-RP ED.     

Diagnostic accuracy of Raman spectroscopy for prostate cancer: a systematic review and meta-analysis

BackgroundAlthough various studies have been conducted to demonstrate the possibility of Raman spectroscopy (RS) as a diagnostic tool for prostate cancer (PC), it is difficult to use it in the real clinical area because of imitations in various research processes. Therefore, we did a systematic review and meta-analysis about the accuracy in diagnostic use of RS for PC.MethodsA literature search was done using PubMed, Embase, and Cochrane library databases in March 2019 to analyze the accuracy of RS for diagnosis of PC. The accuracy of RS for diagnosis of PC was evaluated by means of pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC).ResultsFive studies were included for qualitative analysis by screening the remaining articles according to the inclusion and exclusion criteria by means of a systematic review. The pooled sensitivity and specificity of RS were 0.89 (95% CI: 0.87–0.91) and 0.91 (95% CI: 0.89–0.93), respectively. The overall PLR and NLR were 9.12 (95% CI: 4.15–20.08) and 0.14 (95% CI: 0.07–0.29), respectively. The DOR of RS demonstrated high accuracy (73.32; 95% CI: 18.43–291.73). The area under the curves (AUCs) of SROC curves was 0.93.ConclusionsRS is an optical diagnostic method with high potential for diagnosis and grading of PC and has advantages of real-time and convenient use. In order to consider real-time use of RS in an actual clinical setting, more studies for standardization and generalization of RS performance and analytical method must be conducted.     

神经功能的改善在糖尿病性勃起障碍治疗中的作用

目的探讨改善神经功能在糖尿病性勃起障碍(ED)治疗中的作用。方法:将70名糖尿病性ED患者随机分为Ⅰ组(空白对照组)、Ⅱ组(给予甲钴胺、西洛他唑和十一酸睾酮口服治疗),采用随机、对照试验方法,观察患者神经传导速度和勃起功能的变化。结果:治疗3个月后,Ⅱ组患者腓总神经和胫神经的传导速度较治疗前及对照组患者明显增快,神经功能明显改善(P<0.01),患者的国际勃起功能指数(IIEF)评分明显上升,勃起功能较治疗前及对照组明显改善(与治疗前相比P<0.01,与对照组相比P<0.05),IIEF评分与腓总神经和胫神经的传导速度呈明显正相关。结论:改善神经功能可明显改善糖尿病性ED患者的勃起功能,在治疗ED患者时,应关注患者神经功能的改善。     

Incidence rate of prostate cancer in men treated for erectile dysfunction with phosphodiesterase type 5 inhibitors: retrospective analysis

The purpose of this study was to determine the incidence rate of prostate cancer among men with erectile dysfunction (ED) treated with phosphodiesterase type 5 inhibitors (PDE-5i) over a 7-year period vs. men with ED of the same age and with similar risk factors who were not treated with PDE-5i. In a retrospective review of electronic medical records and billing databases between the years 2000 and 2006, men with ED between the ages of 50 and 69 years and no history of prostate cancer prior to 2000 were identified. These individuals were divided into two groups: 2362 men who had treatment with PDE-5i, and 2612 men who did not have treatment. Demographic data in each group were compared. During the study period, 97 (4.1%) men with ED treated with PDE-5i were diagnosed with prostate cancer compared with 258 (9.9%) men with ED in the non-treated group (P<00001). A higher percentage of African Americans were treated with PDE-5i vs. those who were not (10.5% vs. 7.1% P<0.0001). The PDE-5i group had lower documented diagnosis of elevated prostate-specific antigen (10.0% vs. 13.1% P=0.0008) and higher percentage of benign prostatic hyperplasia (38.4% vs. 35.1% P=0.0149). Men with ED treated with PDE-5i tended to have less chance (adjusted odds ratio: 0.4; 95% confidence intervals: 0.3–0.5; P<0.0001) of having prostate cancer. Our data suggest that men with ED treated with PDE-5i tended to have less of a chance of being diagnosed with prostate cancer. Further research is warranted.     

Penile rehabilitation after prostate cancer treatment: outcomes and practical algorithm

The number of patients diagnosed with prostate cancer was estimated to be 192,000 in 2009 according to the American Cancer Society. The prevalence of reported erectile dysfunction after radical prostatectomy has significant variance. Among the studies in which the nerve-sparing status was described, erectile function recovery adequate for sexual intercourse was achieved in 50% of patients. This article reviews the animal and human studies in this field and provides a useful penile rehabilitation algorithm.     

Narrative review of urinary glycan biomarkers in prostate cancer

Prostate cancer (PC) is the second most common cancer in men worldwide. The application of the prostate-specific antigen (PSA) test has improved the diagnosis and treatment of PC. However, the PSA test has become associated with overdiagnosis and overtreatment. Therefore, there is an unmet need for novel diagnostic, prognostic, and predictive biomarkers of PC. Urinary glycoproteins and exosomes are a potential source of PC glycan biomarkers. Urinary glycan profiling can provide noninvasive monitoring of tumor heterogeneity and aggressiveness throughout a treatment course. However, urinary glycan profiling is not popular due to technical disadvantages, such as complicated structural analysis that requires specialized expertise. The technological development of glycan analysis is a rapidly advancing field. A lectin-based microarray can detect aberrant glycoproteins in urine, including PSA glycoforms and exosomes. Glycan enrichment beads can enrich the concentration of N-linked glycans specifically. Capillary electrophoresis, liquid chromatography-tandem mass spectrometry, and matrix-assisted laser desorption/ionization-time of flight mass spectrometry can detect glycans directory. Many studies suggest potential of urinary glycoproteins, exosomes, and glycosyltransferases as a biomarker of PC. Although further technological challenges remain, urinary glycan analysis is one of the promising approaches for cancer biomarker discovery.     

The influence of prostatic calculi on lower urinary tract symptoms and sexual dysfunction: a narrative review

Prostatic calculi (PC) are commonly found in patients who present for urologic consultation. However, the effect of PC on urinary symptoms remains controversial. In this study, we searched the Embase and PubMed databases for literature related to the following keywords: “prostatic calculi”, “prostatic stone”, “prostatic lithiasis” and “prostatic calcification”, along with the limits, “lower urinary tract symptoms”, “sexual dysfunction”, “erectile dysfunction”, “erectile function”, and “premature ejaculation”. According to the literature, there are various subtypes of PC based on X-ray or ultrasound findings, including type I/II, type A/B, and endogenous PC/extrinsic PC. Furthermore, the formation of PC remains unclear, and more importantly, the ability of PC to cause lower urinary tract symptoms (LUTS) and sexual dysfunction (SD) is worth exploring. We retrospectively reviewed all available literature and found that most studies agreed that PC are associated with LUTS. The factors which may play an important role in the pathogenesis of LUTS include the size and location of PC, induced inflammation, and the blood flow of the prostate. Similarly, SD was also examined in the patients with PC, and psychological factors cannot be ignored in this regard. However, more in-depth study of the molecular mechanisms, including prospective, controlled, longitudinal, and large- sample studies, are needed in the future.     

Extracellular vesicles in prostate cancer: a narrative review

Over the past decade, there has been remarkable progress in prostate cancer biomarker discovery using urine- and blood-based assays. A liquid biopsy is a minimally invasive procedure to investigate the cancer-related molecules in circulating tumor cells (CTCs), cell-free DNA, and extracellular vesicles (EVs). Liquid biopsies have the advantage of detecting heterogeneity as well as acquired resistance in cancer. EVs are cell-derived vesicles enclosed by a lipid bilayer and contain various molecules, such as nucleic acids, proteins, and lipids. In patients with cancer, EVs derived from tumors can be isolated from urine, plasma, and serum. The advances in isolation techniques provide the opportunity to use EVs as biomarkers in the clinic. Emerging evidence suggests that EVs can be useful biomarkers for the diagnosis of prostate cancer, especially high-grade cancer. EVs can also be potent biomarkers for the prediction of disease progression in patients with castration-resistant prostate cancer (CRPC). EVs shed from cancer and stromal cells are involved in the development of tumor microenvironments, enhancing cancer progression, metastasis, and drug resistance. Here, we provide an overview of the use of EVs for the diagnosis of clinically significant prostate cancer as well as for predicting disease progression. We also discuss the biological function of EVs, which regulate cancer progression.     

Sexual function and male cancer

Quality of life in general and sexual functioning in particular have become very important in cancer patients. Biological factors such as anatomic alterations, physiological changes and secondary effect of medical interventions may preclude normal sexual functioning even when sexual desire is intact. In spite of modern surgical techniques, improved chemotherapeutical drugs and sophisticated radiation techniques, still many patients complain of impaired sexual function after cancer treatment. A large number of instruments already exist to assess quality of life in cancer patients. It is important to standardize procedures and to use validated questionnaires. Collecting data on an ongoing basis before and long after treatment is mandatory, and control groups must be used. Patients should be offered sexual counselling and informed about the availability of therapies for sexual dysfunctions. In this paper we review the topic of sexual functioning after treatment (predominantly after radiotherapy) of the most common malignancies in men and give suggestions for treatment.     

Sexual function in the penile cancer survivor: a narrative review

Squamous cell carcinoma of the penis is a rare malignancy among men in North America and Europe with an incidence of <1 per 100,00 men. Of all genitourinary cancers, penile carcinoma has the potential to jeopardize sexual function the most. The treatment modalities of penile carcinoma span the gamut from organ-sparing treatments such as topical therapy, laser therapy, radiotherapy, glansectomy, wide-local excision and partial or total penectomy. There is a relative paucity of data in the medical literature describing the impact of penile cancer treatment on sexual function. The majority of available studies use retrospective data from small samples utilizing heterogeneous study tools such as patient interviews and non-validated questionnaires. The most commonly used validated instrument to evaluate sexual outcomes is the International Index of Erectile Function Questionnaire (IIEF), but is limited in that it does not assess patients who perform self-stimulation or achieve sexual stimulation by any means other than penetrative intercourse. Though advances in clinical research continue; large, well-designed comparative studies using validated instruments are elusive. The sexual outcomes after penile cancer are reviewed from the available published data to better assist the patient and the treating physician with medical decision making. With a detailed assessment of sexual outcomes, the physician is better equipped in providing patient centered care to achieve outcomes meaningful for each patient.     

Current treatment options for newly diagnosed metastatic hormone-sensitive prostate cancer—a narrative review

Prostate cancer continues to be one of the most commonly diagnosed cancers in men globally and a leading cause of male cancer deaths. The landscape of metastatic hormone-sensitive prostate cancer has significantly changed over the past decade. For many years, androgen deprivation therapy alone through surgical or chemical castration was the mainstay of treatment yielding limited 5-year survival rates. New treatment approaches using Docetaxel chemotherapy or androgen receptor pathway inhibitors to intensify upfront systemic therapy have resulted in significantly improved survival rates compared to androgen deprivation therapy alone. Clinicians are now equipped with an arsenal of drugs capable of prolonging life for metastatic hormone-sensitive prostate cancer patients. Furthermore, new treatment modalities are being tested in clinical trials making treatment of metastatic hormone-sensitive prostate cancer an extremely dynamic space. In this narrative review, we provide an overview of the key systemic treatments for metastatic hormone-sensitive prostate cancer, namely androgen deprivation therapy, novel androgen receptor pathway inhibitors and Docetaxel. We summarise a series of landmark trials that have led to the integration of novel androgen receptor pathway inhibitors and docetaxel into the treatment paradigm for metastatic hormone-sensitive prostate cancer. Lastly, we discuss nursing, financial and side-effect considerations pertaining to the use of these drugs. This article aims to give its readers an understanding of the evidence and clinical aspects of novel therapies in metastatic hormone-sensitive prostate cancer as they become increasingly available for use around the world.