Gold nanoshell-localized photothermal ablation of prostate tumors in a clinical pilot device study.

Biocompatible gold nanoparticles designed to absorb light at wavelengths of high tissue transparency have been of particular interest for biomedical applications. The ability of such nanoparticles to convert absorbed near-infrared light to heat and induce highly localized hyperthermia has been shown to be highly effective for photothermal cancer therapy, resulting in cell death and tumor remission in a multitude of preclinical animal models. Here we report the initial results of a clinical trial in which laser-excited gold-silica nanoshells (GSNs) were used in combination with magnetic resonance-ultrasound fusion imaging to focally ablate low-intermediate-grade tumors within the prostate. The overall goal is to provide highly localized regional control of prostate cancer that also results in greatly reduced patient morbidity and improved functional outcomes. This pilot device study reports feasibility and safety data from 16 cases of patients diagnosed with low- or intermediate-risk localized prostate cancer. After GSN infusion and high-precision laser ablation, patients underwent multiparametric MRI of the prostate at 48 to 72 h, followed by postprocedure mpMRI/ultrasound targeted fusion biopsies at 3 and 12 mo, as well as a standard 12-core systematic biopsy at 12 mo. GSN-mediated focal laser ablation was successfully achieved in 94% (15/16) of patients, with no significant difference in International Prostate Symptom Score or Sexual Health Inventory for Men observed after treatment. This treatment protocol appears to be feasible and safe in men with low- or intermediate-risk localized prostate cancer without serious complications or deleterious changes in genitourinary function.

Long-term sexual functioning in germ-cell tumor survivors.

BACKGROUND: Survivors of germ-cell tumors (GCT) may suffer from long-term adverse consequences. Our study was conducted to assess a long-term sexual functioning in GCT survivors. METHODS: GCT survivors (N = 170) from the National Cancer Institute in Slovakia completed a Sexual Function Questionnaire that was modified from PROMIS Sexual Function and Satisfaction Questionnaire 9-year median follow up (range 5-32) as a primary exploratory aim. Study groups consisted of 17 survivors (10%) who had active surveillance (AS, controls), and 153 (90%) survivors who received treatment beyond orchiectomy (Tx), including cisplatin-based chemotherapy (CT, N = 132; 78%), radiotherapy to the retroperitoneal lymph nodes (RT, N = 12; 7%) or both (CTRT, N = 9; 5%). RESULTS: In univariate analysis, treatment of any type resulted in difficulty to maintain erection during sexual intercourse compared to patients treated with AS (P = 0.04). Survivors who received CTRT had lower ability to achieve orgasm during sexual activities (P = 0.04) and they reported disappointment with their overall quality of sex life (P = 0.002). The number of attempts to initiate sexual intercourse did not differ. Sexual relationships caused none or mild anxiety and the desire to be sexually active was higher after CTRT (P = 0.05). Multivariable analysis confirmed that orgasmic dysfunction after ≥400 mg/m2 of cisplatin and issues in maintaining erection after Tx were independent of retroperitoneal lymph-node dissection (P = 0.03 and P = 0.04, respectively). Survivors were disappointed with the quality of sex life and had stronger desire to be sexually active independent of age, (P = 0.01 and P = 0.05, respectively). CONCLUSIONS: This study identified an impairment in sexual function may represent an issue for long-term GCT survivors. Treatment with chemotherapy plus radiotherapy were associated with disappointment and stronger sexual desire, while a higher cumulative dose of cisplatin may be responsible for orgasmic dysfunction.

Extensive Histological Sampling following Focal Therapy of Clinically Significant Prostate Cancer with High Intensity Focused Ultrasound.

PURPOSE: Clinically significant, localized prostate cancer is currently treated with whole gland therapy. This approach is effective but associated with genitourinary and rectal side effects. Focal therapy of prostate cancer has been proposed as an alternative. The aim of this study was to determine the oncologic and functional outcomes of focal high intensity focused ultrasound therapy of prostate cancer. MATERIALS AND METHODS: In this single center, prospective study 75 men were treated between April 2014 and April 2018. Multiparametric magnetic resonance imaging and transperineal template saturation prostate biopsy were performed to localize prostate cancer, followed by focal ablation with high intensity focused ultrasound. The study primary end point was the detection of clinically significant prostate cancer, defined as Gleason score 7 or greater, at 6-month followup transperineal template saturation prostate biopsy. Genitourinary side effects were of secondary interest. RESULTS: Median patient age was 67 years (IQR 60-71) and median prostate specific antigen was 5.87 ng/ml (IQR 4.65-7.44). There were 5 low risk (6.7%) and 70 intermediate risk (93.3%) cancers. Clinically significant prostate cancer was detected in 41% of the men (95% CI 30.3-53.0) who underwent biopsy at 6 months and the median number of sampled cores was 44 (IQR 36-44). Prostate specific antigen (OR 1.17, IQR 0.49-2.85, p=0.71) and multiparametric magnetic resonance imaging (14.3% sensitivity, IQR 6.7-31.5) performed poorly to predict positive biopsies. Pad-free continence and erection sufficient for penetration were preserved in 63 of 64 (98.4%) and 31 of 45 patients (68.9%), respectively. CONCLUSIONS: Focal therapy with high intensity focused ultrasound leads to a low rate of genitourinary side effects. Followup biopsy of treated and untreated prostates remains the only modality to adequately select men in need of early salvage treatment.

Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence.

INTRODUCTION: Sexual function can be impaired by all prostate cancer treatment modalities, but studies specifically addressing the impact of stereotactic body radiotherapy (SBRT) on sexual function are scarce. AIM: To systematically evaluate sexual outcomes in patients treated by SBRT for prostate cancer and determine clinical factors associated with erectile dysfunction (ED). METHODS: A systematic review of the available literature was performed on PubMed/Medline, Scopus, and Cochrane Library databases in June 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Only articles providing data on baseline and post-treatment sexual function after SBRT (≥5 Gy/fraction) were included in this analysis (n = 12). MAIN OUTCOME MEASURE: Sexual function deteriorates after SBRT of the prostate. RESULTS: Deterioration of sexual health was found, with Expanded Prostate Cancer Index Composite-26 sexual domain scores showing a median decrease of 9.2 at 12 months and a median decrease of the Sexual Health Inventory for Men subdomain score by 2.7 at 12 months (from baseline median value of 56.3 and 16, respectively). At 60 months, ED was reported by 26-55% of previously sexually functioning patients in 5 of the 12 studies. CLINICAL IMPLICATIONS: ED affects ≤55% of previously sexually functioning patients at 5 years, as reported for other non-surgical treatment modalities. STRENGTHS & LIMITATIONS: This study enforced strict inclusion criteria of selected studies and exclusion of patients receiving concurrent androgen deprivation therapy. However, inconsistencies in the choice of assessment tool and definition of ED hamper a robust meta-analysis of pooled data. CONCLUSION: Sexual function decline after SBRT for prostate cancer appears to be similar to other modalities and should be specifically addressed in future studies. Loi M, Wortel RC, Francolini G, et al. Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence. J Sex Med 2019;16:1409-1420.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

BACKGROUND: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated. AIM: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model. METHODS: Male rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20. OUTCOMES: Intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis. RESULTS: Following RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased. CLINICAL TRANSLATION: RT-induced ED may result from damage to the ganglia controlling erections. STRENGTHS & LIMITATIONS: This study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point. CONCLUSION: This is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined. Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27-41.

Impact of age on quality of life in patients with localized prostate cancer treated with high-dose rate brachytherapy combined with external beam radiotherapy.

OBJECTIVES: To evaluate age-related quality of life changes in patients with localized prostate cancer treated by high-dose rate brachytherapy combined with external beam radiation therapy. METHODS: A total of 172 patients with clinically localized prostate cancer were categorized to age groups <75 years and ≥75 years. Changes in their quality of life were evaluated using the Japanese version of Medical Outcome Study 8-Items Short Form Health Survey, Expanded Prostate Cancer Index Composite and International Index of Erectile Function-5 at baseline, and followed up to 24 months after treatment. RESULTS: There were no significant differences in Medical Outcome Study 8-Items Short Form Health Survey scores, and urinary and bowel scores of the Expanded Prostate Cancer Index Composite for older men after treatment. International Index of Erectile Function-5 summary scores were significantly decreased in both groups. Although sexual function and sexual bother scores were decreased in patients aged <75 years, these scores were maintained in patients aged ≥75 years. CONCLUSIONS: Quality of life of prostate cancer patients undergoing high-dose rate brachytherapy combined with external beam radiation therapy does not seem to be significantly affected by age.

Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer.

INTRODUCTION: Changes in sexual function other than erectile dysfunction are sparsely investigated after radiation therapy for prostate cancer. AIM: To investigate orgasmic dysfunction, urinary incontinence during sexual activity, changes in penile morphology, and sensory disturbances in the penis in patients with prostate cancer treated with external-beam radiation therapy (EBRT). METHODS: In February 2015, men treated with EBRT at our center 3 months to 5 years previously (N = 519) received a study-specific questionnaire. This was developed from purpose-built questions and validated tools including the Erection Hardness Scale. All patients had received a radiation dose of 78 Gy. Androgen deprivation therapy was administered according to disease characteristics. MAIN OUTCOME MEASURES: Outcome measurements were prevalence rates and predictors of these side effects as identified by multivariate logistic regression analyses. RESULTS: One hundred nine patients were eligible (sexually active and had completed androgen deprivation therapy) for inclusion. Twenty-four percent reported anorgasmia, 44% reported a decreased intensity of their orgasms, and 40% reported that the time it took to reach orgasm had increased. Eleven percent reported anejaculation. Fifteen percent reported orgasm-associated pain. Only 4% reported urinary incontinence during sexual activity. Subjective penile length loss in excess of 1 cm was reported by 42%. Twelve percent reported an altered curvature of their penis after EBRT. Six percent reported painful erections. Twenty-seven percent reported decreased sensitivity in the penis after EBRT, 2% reported a cold sensation, and 2% reported paresthesia. Increasing time since final treatment increased the risk of penile sensory disturbances (odds ratio = 1.05; P = .028). CONCLUSION: Orgasmic dysfunction, changes in penile morphology, and sensory disturbances in the penis are common side effects of ERBT. Patients should be properly informed of the occurrence of these side effects before deciding which treatment to pursue. Frey A, Pedersen C, Lindberg H, et al. Prevalence and Predicting Factors for Commonly Neglected Sexual Side Effects to External-Beam Radiation Therapy for Prostate Cancer. J Sex Med 2017;14:558-565.

Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial.

BACKGROUND: Although several reports have documented the subjective improvement of erectile function after low-intensity extracorporeal shockwave therapy (LI-ESWT) in patients with vasculogenic erectile dysfunction (ED), objective assessment data of penile hemodynamics are lacking. AIM: To assess penile hemodynamics before and 3 months after LI-ESWT in a group of patients with documented vasculogenic ED. METHODS: This was a double-blinded, randomized, sham-controlled trial. Forty-six patients with ED were randomized; 30 underwent LI-ESWT and 16 had a sham procedure in double-blinded fashion. All patients underwent penile triplex ultrasonography by the same investigator immediately before and 3 months after treatment. Patient demographics, International Index of Erectile Function erectile function domain (IIEF-ED) score, and minimal clinically important difference were assessed at baseline and 1, 3, 6, 9, and 12 months after treatment. OUTCOMES: Changes in peak systolic velocity and resistance index as measured by triplex ultrasonography at baseline and 3 months after treatment were the main outcomes of the study. Secondary outcomes were changes in the IIEF-EF score from baseline to 1, 3, 6, 9, and 12 months after treatment and the percentage of patients reaching a minimal clinically important difference during the same period for the two groups. RESULTS: IIEF-EF minimal clinically important differences for the active vs sham group were observed for 56.7% vs 12.5% (P = .005) at 1 month, 56.7% vs 12.5% (P = .003) at 3 months, 63.3% vs 18.8% (P = .006) at 6 months, 66.7% vs 31.3% (P = .022) at 9 months, and 75% vs 25% (P = .008) at 12 months. Mean peak systolic velocity increased by 4.5 and 0.6 cm/s in the LI-ESWT and sham groups, respectively (P < .001). CLINICAL IMPLICATIONS: Such results offer objective and subjective documentation of the value of this novel treatment modality for men with vasculogenic ED. STRENGTHS AND LIMITATIONS: Strengths include the prospective, randomized, sham-controlled type of study and the assessment of penile hemodynamics. Limitations include the small sample and strict inclusion criteria that do not reflect everyday clinical practice. CONCLUSION: The present study confirms the beneficial effect of LI-ESWT on penile hemodynamics and the beneficial effect of this treatment up to 12 months. Kalyvianakis D, Hatzichristou D. Low-Intensity Shockwave Therapy Improves Hemodynamic Parameters in Patients With Vasculogenic Erectile Dysfunction: A Triplex Ultrasonography-Based Sham-Controlled Trial. J Sex Med 2017;14:891-897.

Longitudinal changes in erectile function after thulium:YAG prostatectomy for the treatment of benign prostatic obstruction: a 1-year follow-up study.

This study aimed to evaluate the impact of thulium:yttrium-aluminum-garnet (Tm:YAG) (RevoLix®) laser prostatectomy for the treatment of benign prostatic obstructions on erectile function (EF). A total of 208 patients who underwent Tm:YAG laser prostatectomies participated in this study. All cases were evaluated preoperatively and at 3, 6, and 12 months postoperatively using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, and the International Index of Erectile Function (IIEF-5) questionnaires. Patients were divided into groups A (severe erectile dysfunction [ED]), B (moderate ED), and C (mild-to-normal ED), according to their IIEF-5 scores. The median patient ages were 69, 65, and 62 years in groups A, B, and C, respectively. Significant improvements occurred in the IPSS and QoL score within the groups during the 12-month follow-up period. The IIEF-5 scores at 3 months postoperatively were lower than the preoperative scores in groups B and C. The IIEF-5 scores subsequently improved during the 12-month follow-up period. The slope of the relationship between the IIEF-5 score and the time since Tm:YAG laser prostatectomy had a ß value of 0.2210 (95% confidence interval 0.103 to 0.338, p = 0.0003); hence, each postoperative month was associated with an increase of 0.2210 in the IIEF-5 score. The IIEF-5 scores gradually increased and reached the preoperative levels by the 12-month follow-up assessment. Although the IIEF-5 score dropped significantly during the first 3 months postoperatively, it improved over the following 12 months. Tm:YAG laser prostatectomy did not impact on EF ultimately.

Assessment of sexual function in Japanese men with prostate cancer undergoing permanent brachytherapy without androgen deprivation therapy: Analysis from the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation database.

OBJECTIVES: To evaluate male sexual function in Japanese prostate cancer patients undergoing permanent brachytherapy without endocrine treatment, using quality of life measures of the Expanded Prostate Cancer Index Composite. METHODS: A total of 482 patients were selected as analysis subjects from the nationwide database for the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation. The patients were asked to complete the Expanded Prostate Cancer Index Composite questionnaires before and at 3, 12, 24, and 36 months after the permanent brachytherapy. Changes in their responses were analyzed, and any association of the outcomes was investigated. Furthermore, changes over time in their answers to Q18 (usual quality of your erections) were analyzed. RESULTS: A total of 72 patients (14.9%) had received external beam radiation. A total of 68 patients (14.1%) had taken any 5-phosphodiesterase inhibitor medications. Regarding Q18, 232 patients (48.2%) selected either "There was no sexual activity" or "There was no desire for erection" before receiving permanent brachytherapy. Of all the 482 patients, sexual function was preserved in 138 patients (28.7%) 3 years after permanent brachytherapy. Overall satisfaction has significantly improved without regard for the deterioration of sexual function. Significant factors for maintaining sexual activity were patient age and sexual activity before permanent brachytherapy. CONCLUSIONS: In Japanese patients undergoing permanent brachytherapy alone for prostate cancer, the sexual function is not well preserved. However, decreased sexual function does not seem to represent a major factor determining patients' overall satisfaction. These findings might be peculiar to Japanese patients, in whom elderly subjects account for the majority.

Sexual Function After Hypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Cancer: Results From the Randomized Phase III HYPRO Trial.

INTRODUCTION: Hypofractionated radiotherapy could increase the radiobiological tumor dose for localized prostate cancer. The effects of hypofractionation on sexual function are not well known. AIM: To compare sexual function in patients with prostate cancer treated with 78 Gy in 39 fractions of 2 Gy or 64.6 Gy in 19 fractions of 3.4 Gy. METHODS: In total, 820 men with intermediate- to high-risk T1b-T4NX-0MX-0 prostate cancer were enrolled in the phase III HYPRO trial (2007-2010) and randomized to conventional fractionation (39 × 2 Gy) or hypofractionation (19 × 3.4 Gy). Sexual function was assessed at baseline and at 6, 12, 24, and 36 months after treatment using the International Index of Erectile Function (IIEF). For this analysis, patients (n = 322) with a baseline assessment, at least one follow-up assessment, and no or short-term (6-month) androgen-deprivation therapy were included. MAIN OUTCOME MEASURES: Mean IIEF domain scores were compared between treatments in the total population and the hormone-naïve population (n = 197) using the independent t-test. Incidences of severe erectile dysfunction (domain score < 11) at last follow-up were calculated in patients with partial or full baseline function. Binary logistic regression analyses were applied to calculate the odds ratio of hypofractionation vs conventional fractionation and to adjust for clinical factors. RESULTS: Median age was 71 years (interquartile range = 67-71) and median follow-up was 37 months (interquartile range = 25-38). Androgen-deprivation therapy was prescribed in 125 (39%). IIEF domain scores decreased after treatment but were comparable between treatment arms at baseline and during follow-up. Orgasmic function scores in hormone-naïve patients were significantly higher at 3 years after hypofractionation (4.08 vs 2.65, P = .031). In patients (n = 120) with partial or full baseline erectile function, the incidence of erectile dysfunction at last follow-up was 34.4% for hypofractionated treatment vs 39.3% for conventional treatment (adjusted odds ratio = 0.84, 95% CI = 0.37-1.90, P = .67). CONCLUSION: No significant differences in erectile functioning between conventional and hypofractionated radiotherapy were found. Hormone-naïve patients reported significantly higher orgasmic function scores at 3 years after hypofractionation.

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

BACKGROUND: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. RESULTS: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

Orchiectomy and radiotherapy for stage I-II testicular seminoma: a prospective evaluation of short-term effects on body image and sexual function.

INTRODUCTION: Orchiectomy followed by infradiaphragmatic radiotherapy is a common treatment for stage I-II testicular seminoma. Long-term effects of orchiectomy and radiotherapy for testicular seminomas on body image and sexual function have been reported; however, few data are available on short-term effects. Patients are usually of reproductive age and sexually active; therefore, short-term effects on body image and sexual function should also be studied. AIMS: To prospectively evaluate short-term effects of orchiectomy and radiotherapy on body image and sexual function in testicular seminoma patients. METHODS: Questionnaires on body image and sexual function were prospectively distributed to all testicular seminoma patients treated between 1999 and 2013. The questionnaire distributed prior to radiotherapy was returned by 161 patients; 133 (82%) returned the second after 3 months, and 120 (75%) completed the questionnaire after 6 months. MAIN OUTCOME MEASURES: Body image and sexual function as assessed by a Dutch questionnaire on body image and sexuality after radiotherapy and orchiectomy. RESULTS: Median age was 36 years (range 18-70). After orchiectomy, 48% expressed fertility concerns, and 61% reported their body had changed. Six months after treatment, erectile rigidity was significantly decreased compared with prior to radiotherapy (P = 0.016), and 23% reported decreased sexual interest, activity, and pleasure. Changes in body image were significantly associated with decreased sexual interest, pleasure, and erectile function. Even though 45% reported that treatment negatively affected their sexual life, the number of sexually active patients remained stable at 91%. [Correction added on 12 November 2014, after first online publication: 'prior radiotherapy' was corrected to 'prior to radiotherapy'.] CONCLUSIONS: Short-term effects of treatment included fertility concerns and changes in body image. Reported erectile rigidity was significantly decreased after 6 months, as were sexual interest, activity, and pleasure. Disease and treatment had negative effects on sexual life, and changes in body image were associated with sexual dysfunction. Therefore, body image and sexual functioning should be addressed at an early stage in order to offer adequate treatment and counseling.

Five-year potency preservation after iodine-125 prostate brachytherapy.

BACKGROUND: We aimed to evaluate long-term erectile function following prostate brachytherapy, based on patient characteristics and treatment factors. METHODS: Between 2003 and 2006, 665 men with localized prostate cancer were treated with (125)I permanent seed implantation. None was given adjuvant hormone therapy. Erectile function was assessed before treatment, and at 6 months, 1, 2, 3, 4 and 5 years after implantation using the Mount Sinai Erectile Function Score (MSEFS) of 0-3 (0 = no erections, 1 = erections insufficient for intercourse, 2 = suboptimal erections but sufficient for intercourse, 3 = normal erectile function). Potency was defined as score 2 or 3, and 382 men were potent before treatment. Univariate and multivariate analyses were performed on the data from these 382 patients to identify variables associated with potency preservation. RESULTS: In patients who were potent before treatment, the actuarial potency preservation rate fell to 46.2 % at 6 months after brachytherapy, and then slowly recovered reaching 52.0 % at 5 years after brachytherapy. In multivariate logistic regression analysis, patient age (p = 0.04) and pre-treatment MSEFS (p < 0.001) were predictors of 5-year potency preservation. Neoadjuvant hormone therapy affected potency preservation only at 6 months after brachytherapy. CONCLUSIONS: Patient age at implantation and pre-treatment erectile function are predictive factors for the development of erectile dysfunction following prostate brachytherapy.

A prospective longitudinal survey of erectile dysfunction in patients with localized prostate cancer treated with permanent prostate brachytherapy.

PURPOSE: Few studies have evaluated changes in erectile function with time before and after prostate brachytherapy using the International Index of Erectile Function-15, a sensitive, validated tool for assessing male sexual dysfunction. In this prospective study we evaluated the natural history of erectile function after prostate brachytherapy without supplemental therapy (external beam radiotherapy, phosphodiesterase-5 inhibitors or androgen deprivation therapy) using the International Index of Erectile Function-15. MATERIALS AND METHODS: We identified 119 patients who were followed at least 12 months after prostate brachytherapy between 2004 and 2010. Sexual and erectile function status were assessed before brachytherapy (baseline), and 3, 6, 12, 18, 24 and 36 months postoperatively using the International Index of Erectile Function-15. RESULTS: Mean total International Index of Erectile Function-15 score, and scores on the erectile function, orgasmic function, sexual desire and intercourse satisfaction domains 3 months after brachytherapy were significantly lower than at baseline (p <0.05). They remained lower until 36 months after prostate brachytherapy. Erectile function was maintained 12 months after brachytherapy in 16 of the 48 men (33.3%) with a baseline erectile function domain score of 11 or greater. There was no significant difference in clinical features except the age of patients who maintained the erectile function domain score and their counterparts 12 months after brachytherapy. Multivariate analysis revealed that age 70 years or greater was the only predictive factor for deteriorating erectile function after brachytherapy (p = 0.035). CONCLUSIONS: Findings indicate a global decrease in all domains of the International Index of Erectile Function-15 score 12 months after prostate brachytherapy. Also, patient age may influence the preservation of brachytherapy related potency.

Ejaculation profiles of men following radiation therapy for prostate cancer.

OBJECTIVES: Radical prostatectomy (RP) is associated with anejaculation, which for some men is a source of bother and sexual dissatisfaction. Clinical experience has shown us some men after pelvic radiation therapy (RT) also experience anejaculation. This analysis was conducted to define the ejaculation profiles of men after RT for prostate cancer (PCa). METHODS: As a routine part of the sexual health evaluation for post-RT patients, men provided information regarding their ejaculatory function and orgasm. Analysis was conducted of a sexual medicine database reviewing demographic data, PCa factors, erectile, ejaculatory, and orgasmic function. Men with prior history of RP, cryotherapy, focal therapies, and androgen deprivation therapy (ADT) were excluded. Patients completed the International Index of Erectile Function (IIEF) questionnaire at follow-up visits commencing with the first posttreatment visit and specific attention was paid to the IIEF orgasm domain. RESULTS: Three hundred and sixty-four consecutive patients were included. Two hundred and fifty-two patients had external beam, and 112 patients had brachytherapy (BT). Mean age was 64 ± 11 (42-78) years and mean follow-up after RT was 6 ± 4.5 years. Mean prostate size at time of RT was 42 ± 21 g. Of the entire population, 72% lost the ability to ejaculate in an antegrade fashion after prostate RT by their last visit. The proportion experiencing anejaculation at 1, 3, and 5 years after RT was 16%, 69%, and 89%, respectively. For men with at least two IIEF questionnaires completed, the orgasm domain scores decreased dramatically over the follow-up period; orgasm domain scores (0-10): <12 months post-RT 7.4, 13-24 months 5.4, 25-36 months 3.2, >36 months 2.8 (P < 0.01). Multivariable analysis identified several factors predictive of failure to ejaculate: older age, ADT, RT dose > 100 Gy, and smaller prostates at the time of RT. CONCLUSIONS: The vast majority of men after prostate RT will experience anejaculation and should be counseled accordingly prior to undergoing therapy. We have identified predictive factors.

Long-term potency preservation following brachytherapy for prostate cancer.

UNLABELLED: Study Type - Therapy (case series). Level of Evidence 4. What's known on the subject? and What does the study add? Previously, rates of potency preservation with or without external beam radiation and/ or hormone therapy have been published with smaller series and limited follow-up. The study provides greater numbers and longer follow-up giving patients and clinicians a better appreciation of the true potency preservation rates in this population and how various factors such as age, hormone use and external beam affect those rates. OBJECTIVES: • To assess potency preservation in men following brachytherapy for prostate cancer with or without external beam radiation therapy (EBRT) and/or androgen deprivation therapy (ADT). • To evaluate the factors that significantly impact this rate. PATIENTS AND METHODS: • In all, 1063 potent men with T1-T3 prostate cancer were treated from 1990 to 2007 with seed implantation alone ((103) Pd or (125) I) (69.6%) or combined modality treatment consisting of a partial dose (103) Pd implant followed 6-8 weeks later by EBRT (45 Gy, prostate/seminal vesicles only) (30.4%). ADT was used in 49.1% of cases (range 1-27 months). • Patients were required to have a minimum of 2 years follow-up and to be off ADT for a minimum of 1 year. • Erectile function was assessed prior to seed implantation and at each follow-up visit using the physician-assigned Mount Sinai Erectile Function Score (MSEFS): 0, unable to have erections; 1, erections insufficient for intercourse; 2, suboptimal erections but sufficient for intercourse; 3, normal erectile function. Potent was defined as a score of greater than or equal to 2 with or without use of a phosphodiesterase type 5 inhibitor. • The potency rate was calculated using actuarial methods with comparisons tested by log-rank and Cox regression analysis. RESULTS: • The 5-year and 10-year actuarial rate of potency preservation was 68.0% and 57.9%, respectively, at last follow-up. • On multivariate analysis, 5- and 10-year potency was 87.6% (79.5%) for men younger than 60, 68.0% (57.5%) for age 60-70, and 42.2% (31.0%) for men older than 70 (P < 0.001). • Pretreatment MSEFS of 2 had a potency rate of 51.7% (37.2%) vs 74.2% (65.2%) for an MSEFS of 3 (P < 0.001). • There was a 75.8% (62.6%) potency rate without ADT vs 60.0% (53.0%) with ADT (P < 0.001). • Five-year potency was 76.4% for implant alone, 71.0% for implant with EBRT, 62.2% for implant with ADT, and 57.9% for implant with EBRT and ADT (P < 0.001). CONCLUSION: • Increasing initial age at implant, diminished pretreatment erectile function and the use of combination therapy with EBRT and/or ADT significantly increases erectile dysfunction following brachytherapy.

Radiation therapy in Peyronie's disease.

INTRODUCTION: Peyronie's disease (PD) is characterized by fibrotic plaque formation within the tunica albuginea, leading to penile deformity, angulation, painful erections, and often, erectile dysfunction. There is limited knowledge of its etiology and pathophysiology. Currently, there is no standardization for reporting the evaluation and treatment outcomes. No consensus exists on the ideal management of PD. AIM: The aim of this study is to review the use of radiation therapy (RT) for the treatment of PD. METHODS: This study used a review of the literature and informed expert opinion. MAIN OUTCOME MEASURES: The main outcome measures are the reported improvement with regard to pain, curvature, plaque size, and erectile function as well as a review of the safety profile of RT. RESULTS: Radiation has been used for the empirical treatment of PD with mixed results throughout the literature. Low-dose RT in the early stages of PD seems to be effective in patients with painful erections not improving with time or with the use of oral or intralesional therapies. Comparison with other current medical therapies is difficult due to the absence of criteria for therapeutic success and the absence of randomized, controlled trials. Multiple studies have demonstrated varied results in terms of curvature reduction, plaque volume, and sexual functioning. The absence of the use of validated means of measuring penile deformity and sexual function, the limited relevance of plaque and pain improvement combined with the potential negative consequences of radiation on erectile tissue structure and function lead us to make a recommendation that RT not be used for the management of PD. CONCLUSIONS: In clinical practice, mixed success for RT has led to the recommendation against its use as a treatment modality for PD.

Effects of intravenous injection of adipose-derived stem cells in a rat model of radiation therapy-induced erectile dysfunction.

INTRODUCTION: Radiation therapy (RT) for prostate cancer is frequently associated with posttreatment erectile dysfunction (ED). AIM: To investigate whether injection of adipose-derived stem cells (ADSCs) can ameliorate RT-associated ED. METHODS: Thirty male rats were divided into three groups. The control + phosphate-buffered saline (PBS) group received tail-vein injection of PBS. The radiation + PBS group received radiation over the prostate and tail-vein injection of PBS. The radiation + ADSC group received radiation over the prostate and tail-vein injection of ADSCs, which were labeled with 5-ethynyl-2-deoxyuridine (EdU). Seventeen weeks later, erectile function was evaluated by intracavernous pressure (ICP) in response to electrostimulation of cavernous nerves (CNs). Penile tissue and major pelvic ganglia (MPG) were examined by immunofluorescence (IF) and EdU staining. MAIN OUTCOME MEASURES: Erectile function was measured by ICP. Protein expression was examined by IF, followed by image analysis and quantification. RESULTS: Radiation over the prostate caused a significant decrease in erectile function and in the expression of neuronal nitric oxide synthase (nNOS) in penis and MPG. Cavernous smooth muscle (CSM) but not endothelial content was also reduced. Injection of ADSCs significantly restored erectile function, nNOS expression, and CSM content in the irradiated rats. EdU-positive cells were visible in MPG. CONCLUSIONS: Radiation appears to cause ED via CN injury. ADSC injection can restore erectile function via CN regeneration.

Assessment of late urinary, bowel and sexual function after dose escalation from 70 to 76 Gy using image-guided radiotherapy in curative treatment of prostate cancer.

OBJECTIVE: The aim of this study was to evaluate the late urinary, bowel and sexual function among men with localized or locally advanced prostate cancer treated with curative radiotherapy after the introduction of image-guided radiotherapy to 76 Gy using the Swedish BeamCath® technique. MATERIAL AND METHODS: All patients treated with curative radiotherapy during 2003-2006 were invited to participate in this retrospective study. In total, 87% (158/181) participated in the study. The median observation time was 35 months. Comparisons were made between the standard 70 Gy (n = 73) and the 76 Gy (n = 85) treatment groups. Assessments of late urinary, bowel and sexual function were questionnaire based, and included function items in the Expanded Prostate Cancer Index Composite. RESULTS: Most late urinary and bowel symptoms were reported to occur seldom or never in the majority of men, while late sexual toxicity was reported in a large proportion (66%) of men. Seven men (4%) used diapers. Only 25% (n = 40) reported having an erection firm enough for intercourse. None of the reported urinary or sexual function symptoms differed between the treatment groups. Rectal urgency at least once daily was a more frequent symptom in the 70 Gy group than the 76 Gy group (28% vs 9%, p = 0.006). Painful bowel movements were a more common symptom in the 70 Gy group (11% vs 1%, p = 0.01). CONCLUSION: Dose escalation up to 76 Gy using the BeamCath technique was not associated with more late toxicities than the standard 70 Gy dose.