Long-term Overall Survival after External Beam Radiotherapy for Localised Prostate Cancer.

AIMS: Knowledge on survival probabilities is essential for determining optimal treatment strategies. We studied overall survival and associated prognostic factors in Dutch patients with localised prostate cancer (PCa) selected for external beam radiotherapy. MATERIALS AND METHODS: For this single-centre retrospective cohort study, we identified all T1-T3 PCa patients (aged 55-80 years) in the radiotherapy planning database with a start date between January 2006 and December 2013, treated with 72-78 Gy in 2 Gy fractions to the prostate ± seminal vesicles (n = 1536). Long-term androgen deprivation therapy (ADT) was predominantly prescribed in the case of extracapsular disease (>T3). Overall survival was estimated using the Kaplan-Meier method. Prognostic factors were evaluated in Cox regression models for the intermediate-risk and high-risk groups. RESULTS: The median follow-up was 12 years for patients who were alive. Ten-year survival rates were 79.0% for low-risk (n = 120), 59.9% for intermediate-risk (n = 430) and 56.8% for high-risk patients (n = 986). A higher age, higher comorbidity score, active smoking and Gleason score ≥8 had a statistically significant negative impact on overall survival at multivariable analysis. ADT was associated with superior overall survival in the high-risk group translating into overall survival rates similar to the intermediate-risk group. CONCLUSIONS: Although PCa patients selected for external beam radiotherapy are typically in good health, their comorbidity score and smoking habits appeared to be dominant predictors for overall survival. Overall survival rates within the high-risk group varied, showing improved overall survival with ADT prescription and worse overall survival in the case of Gleason score ≥8.

Acute and late toxicity patterns of moderate hypo-fractionated radiotherapy for prostate cancer: A systematic review and meta-analysis.

Introduction: Moderate hypofractionated (HF) radiotherapy is becoming the new standard in radiotherapy for prostate cancer patients. It is established as safe, but it might be associated with increased acute toxicity levels. We conducted a systematic review on moderate HF to establish acute toxicity levels and their required clinical management; late toxicity was reported as a secondary outcome. Material and methods: Using PRISMA guidelines, we conducted a systematic review for studies published until June 2022. We identified 17 prospective studies, with 7796 localised prostate cancer patients, reporting acute toxicity of moderate hypofractionation (2.5-3.4 Gy/fraction). A meta-analysis was done for 10/17 studies with a control arm (standard fractionation (SF)), including evaluation of late toxicity rates. We used Cochrane bias assessment and Newcastle-Ottawa bias assessment tools for randomized controlled trials (RCTs) RCT and non-RCTs, respectively. Results: Pooled results showed that acute grade ≥ 2 gastro-intestinal (GI) toxicity was increased by 6.3 % (95 % CI for risk difference = 2.0 %-10.6 %) for HF vs SF. Acute grade ≥ 2 Genito-urinary (GU) and late toxicity were not significantly increased. The overall risk of bias assessment revealed a low risk in the meta-analysis of included studies. Data on management of toxicity (medication, interventions) was only reported in 2/17 studies. Conclusion: HF is associated with increased acute GI symptoms, needing adequate monitoring and management. Reports on toxicity management were very limited. Pooled late GI and GU toxicity showed similar levels for SF and HF.

Impact of Advanced External Beam Radiotherapy on Second Haematological Cancer Risk in Prostate Cancer Survivors.

AIMS: External beam radiotherapy (EBRT) for prostate cancer (PCa) has rapidly advanced over the years. Advanced techniques with altered dose distributions may have an impact on second haematological cancer (SHC) risks. We assessed SHC risk after EBRT for PCa and explored whether this risk has changed over the years. MATERIALS AND METHODS: Patients diagnosed with a T1-T3 PCa between 1990 and 2015 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were assigned to EBRT eras based on the date of diagnosis. These eras represented two-dimensional radiotherapy (2D-RT; 1991-1996), three-dimensional conformal radiotherapy (3D-CRT; 1998-2005) or advanced EBRT (2008-2015). Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated overall and by EBRT era. Sub-hazard ratios (sHRs) were calculated for the comparison of EBRT versus radical prostatectomy and active surveillance. RESULTS: PCa patients with EBRT as the primary treatment (n = 37 762) had an increased risk of developing a SHC (SIR = 1.20; 95% confidence interval 1.13-1.28) compared with the Dutch male general population. Estimated risks were highest for the 2D-RT era (SIR = 1.32; 95% confidence interval 1.14-1.67) compared with the 3D-CRT era (SIR = 1.16; 95% confidence interval 1.05-1.27) and the advanced EBRT era (SIR = 1.21; 95% confidence interval 1.07-1.36). AER were limited, with about five to six extra cases per 10 000 person-years. Relative risk analysis (EBRT versus radical prostatectomy/active surveillance) showed significant elevation with EBRT versus active surveillance (sHR = 1.17; 95% confidence interval 1.03-1.33; P = 0.017), but not for EBRT versus radical prostatectomy (sHR = 1.08; 95% confidence interval 0.94-1.23; P = 0.281). CONCLUSION: Increased SHC risks after EBRT for PCa cancer were observed for all EBRT eras compared with the general Dutch male population. Excess risks for EBRT versus other PCa treatment groups were found for only EBRT versus active surveillance.

Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress.

INTRODUCTION: The etiology of radiation-induced erectile dysfunction (ED) is complex and multifactorial, and it appears to be mainly atherogenic. AIM: To focus on vascular aspects of radiation-induced ED and to elucidate whether the protective effects of sildenafil are mediated by attenuation of oxidative stress and apoptosis in the endothelial cells. METHODS: Bovine aortic endothelial cells (BAECs), with or without pretreatment of sildenafil (5 µM at 5 minutes before radiation), were used to test endothelial dysfunction in response to external beam radiation at 10-15 Gy. Generation of reactive oxygen species (ROS) was studied. Extracellular hydrogen peroxide (H2O2) was measured using the Amplex Red assay and intracellular H2O2 using a fluorescent sensor. In addition, ROS superoxide (O2•-) was measured using a O2•- chemiluminescence enhancer. Both H2O2 and O2•- are known to reduce the bioavailability of nitric oxide, which is the most significant chemical mediator of penile erection. Generation of cellular peroxynitrite (ONOO-) was measured using a chemiluminescence assay with the PNCL probe. Subsequently, we measured the activation of acid sphingomyelinase (ASMase) enzyme by radioenzymatic assay using [14C-methylcholine] sphingomyelin as substrate, and the generation of the proapoptotic C16-ceramide was assessed using the diacylglycerol kinase assay. Endothelial cells apoptosis was measured as a readout of these cells' dysfunction. MAIN OUTCOME MEASURES: Single high-dose radiation therapy induced NADPH oxidases (NOXs) activation and ROS generation via the proapoptotic ASMase/ceramide pathway. The radio-protective effect of sildenafil on BAECs was due to inhibition of this pathway. RESULTS: Here, we demonstrate for the first time that radiation activated NOXs and induced generation of ROS in BAECs. In addition, we showed that sildenafil significantly reduced radiation-induced O2•- and as a result there was reduction in the generation of peroxynitrite in these cells. Subsequently, sildenafil protected the endothelial cells from radiation therapy-induced apoptosis. STRENGTHS AND LIMITATIONS: This is the first study demonstrating that single high-dose radiation therapy induced NOXs activation, resulting in the generation of O2•- and peroxynitrite in endothelial cells. Sildenafil reduced ROS generation by inhibiting the ASMase/ceramide pathway. These studies should be followed in an animal model of ED. CONCLUSIONS: This study demonstrated that sildenafil protects BAECs from radiation-induced oxidative stress by reducing NOX-induced ROS generation, thus resulting in decreased endothelial dysfunction. Therefore, it provides a potential mechanism to better understand the atherogenic etiology of postradiation ED. Wortel RC, Mizrachi A, Li H, et al. Sildenafil Protects Endothelial Cells From Radiation-Induced Oxidative Stress. J Sex Med 2019;16:1721-1733.

Microbially-enhanced composting of wet olive husks.

The production of a compost from olive wet husks is described. The process is enhanced through the use of starters prepared with virgin husks enriched with selected microbial cultures. This approach, with respect to composting without the use of starters, allows to achieve faster start of the process (10 vs. 45 days), deeper humification (humification rate 19.2 vs. 12.2), shorter maturation time (2 vs. 4-5 months) and better detoxification of the starting material. Furthermore, the compost produced can effectively substitute for turf as a cultivation substrate in horticulture at greenhouse level, with beneficial effects on nutraceutical traits of tomato fruits.

[Favorable effect of sildenafil on erectile dysfunction in patients after radiotherapy for prostate cancer; randomised, double-blind, placebo-controlled crossover study]. / Gunstig effect van sildenafil op erectiele disfunctie bij patiënten na radiotherapie voor prostaatkanker; gerandomiseerd, dubbelblind, placebogecontroleerd en gekruist onderzoek.

OBJECTIVE: To determine the efficacy of sildenafil in patients with erectile dysfunction after external beam radiotherapy for prostate cancer. DESIGN: Randomised, double-blind, placebo-controlled, crossover study. METHOD: A total of 406 patients with erectile dysfunction reported in their medical records who had completed external beam radiotherapy at least 6 months prior to the study, were approached by letter. Sixty patients were included in a study which lasted 12 weeks. They received 50 mg of sildenafil citrate or placebo for two weeks; during week 2 the dose could be increased to 100 mg in the case of unsatisfactory erectile response. At week 6 patients crossed over to the alternative treatment. Data were collected using the validated 'International index of erectile function' (IIEF) questionnaire, and side-effects were recorded. Patients were given the possibility of continuing to a 6-week open-label phase. RESULTS: The mean age of those participating was 68 years. All patients completed the double-blind phase. For the majority f questions in the IIEF questionnaire, there was a significant increase in mean scores from baseline with sildenafil, but of the patients with sildenafil, versus 18% with placebo. Ninety percent of the patients required a dose adjustment to 100 mg sildenafil, and 100% of the patients in the placebo group increased the dose. Side-effects were mild or moderate. Patients who proceeded to the open-label phase reported the same results as in the double-blind phase. CONCLUSION: Sildenafil improved erectile function in about half of the patients with erectile dysfunction after external beam radiotherapy for prostate cancer, and it was well tolerated.

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study.

PURPOSE: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer. METHODS AND MATERIALS: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded. RESULTS: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate. CONCLUSION: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.

Sexual functioning in patients with localized prostate cancer awaiting treatment.

This article evaluates current sexual functioning in patients with prostate cancer who are awaiting treatment. One-hundred fifty-eight patients filled out a 15-item questionnaire regarding current sexual functioning. Median age was 67 years. Sixty percent reported to have spontaneous erections at least once a week, and 37% reported a good firmness. Thirty-five percent reported that during sexual activity they had no difficulty in getting erections, and 33% reported that they had no difficulty in maintaining an erection. After diagnosis, all patients reported a decrease in sexual interest, activity, and pleasure. Diagnosis of prostate cancer does have an impact on sexual functioning, therefore sexual counseling prior to treatment is advised.

Low-dose radiotherapy in 179 patients with Peyronie's disease: treatment outcome and current sexual functioning.

PURPOSE: To analyse retrospectively treatment outcome in patients irradiated for Peyronie's disease. METHODS AND MATERIALS: The records of 179 patients, median age 52 years, that received radiotherapy (RT) between 1982 and 1997 were reviewed. 78% presented with painful erections and 89% with penile deformity. The symptoms were present for a median duration of 6 months (range, 1-72 months). The RT schedule consisted of 13.5 Gy (9 x 1.5 Gy, 3 fractions per week) using orthovoltage X-rays in 123 patients or 12 Gy (6 x 2 Gy, daily fractions) using electrons in 56 patients. A questionnaire regarding current sexual functioning was mailed to 130 patients whose addresses could be traced; 106 (82%) responded. RESULTS: At mean follow-up period of 3 months, 83% reported that pain was diminished or had disappeared after RT. Twenty-three percent of patients reported a decrease in penile deformity. Following RT, surgical correction of penile curvature was performed in 29% of patients. No RT-related complications occurred except transient dysuria in 1 patient. Questionnaire data: 72% of patients were currently sexually active, 48% had erectile dysfunction, and 49% expressed dissatisfaction with their current sexual functioning. CONCLUSION: Low-dose external RT (12-13.5 Gy) results in relief of pain in the majority of patients with Peyronie's disease. Improvement in penile deformity was observed, avoiding surgery in a number of patients. No significant RT-associated morbidity was encountered. It is disappointing that almost 50% of patients complain of sexual functioning, but this is presumably not related to radiotherapy.

Current sexual functioning in 106 patients with Peyronie's disease treated with radiotherapy 9 years earlier.

OBJECTIVES: To analyze retrospectively the sexual functioning and treatment outcome in patients after radiotherapy (RT) for Peyronie's disease. METHODS: During 1982 to 1997, 179 patients with Peyronie's disease were treated at our radiation oncology department. One hundred thirty patients whose address could be traced were sent a questionnaire about their symptoms before RT, treatment outcome, and current sexual functioning (the past 4 weeks). One hundred six patients, mean age 59 years, responded. RESULTS: Before RT, 44% reported painful erections, 97% penile curvature, and 18% erectile dysfunction. Sixty-nine percent reported that after RT, penile pain was diminished and 29% that penile curvature was decreased; 13% reported improved erections. With respect to their current sex life, 51% reported sometimes or always having problems getting an erection and 61% in maintaining an erection; 36% never experienced spontaneous erections. Fifty-four percent reported not having erections rigid enough for sexual activity. Since RT (mean 9 years), there had been a moderate or severe decrease in sexual interest (17%), sexual activity (41%), and sexual pleasure (32%). Overall, 49% of patients were dissatisfied with their current sexual functioning. CONCLUSIONS: Low-dose external RT resulted in relief of pain in two thirds of patients with Peyronie's disease. An improvement in penile curvature was reported in one third of patients. One half of men reported problems in getting an erection. The rigidity of erections was satisfactory in only 54%. There was a moderate to severe decrease in sexual interest, activity, and pleasure after RT; however, this was associated with age, although comorbidity or medications cannot be excluded.

Testicular prostheses: body image and sexual functioning.

OBJECTIVES: To evaluate retrospectively the body image and sexual functioning in patients who have a testicular prosthesis (TP). PATIENTS AND METHODS: The medical charts were evaluated for 30 adult patients who received 32 TPs between 1985 and 1997. A questionnaire was mailed to each patient, asking about body image, satisfaction with the implant and with sexual functioning. RESULTS: Of the 30 patients, 22 (73%) replied; their mean (range) age was 30 (18-47) years. Most of the patients had a silicone gel-filled TP. No complications were reported in 25 (83%) patients and 80% reported no sexual problems; 20% felt uncomfortable in intimate contacts, 68% found their body image improved after having a TP, 58% were satisfied with their current sexual life, 90% had no erectile dysfunction and 45% reported premature ejaculation. CONCLUSIONS: Patients who have lost a testis for any reason should be informed about the availability of a TP. Prostheses were well accepted and no systemic disease was reported. Almost all patients reported an improvement in their body image. Sexual life and performance were apparently not compromised by having a TP. New surgical procedures are recommended to improve the cosmetic appearance of a TP in the scrotum.

Visual erotic and vibrotactile stimulation and intracavernous injection in screening men with erectile dysfunction: a 3 year experience with 406 cases.

To establish the number of patients with erectile dysfunction (ED) who appear to be sexually potent when exposed to visual erotic (VES) and vibrotactile stimulation (VIB) and to investigate whether or not older patients are less responsive to VES/VIB than young patients. Retrospective analysis of data on 406 consecutive patients screened for ED with VES, VES + VIB, VES + Intracavernous injection (ICI). Partial or full erection was obtained in 34% of patients with VES, 52% with VES + VIB, 82% with VES + ICI. Men < 40 y (n = 86) responded better than men > 40; between 40 and 80 no differences in penile responses were found. 50% of patients who reported no morning/night erections appeared to have good, rigid nocturnal penile tumescence (NPT). The use of VES, VES + VIB, VES + ICI is strongly recommended in the screening of men with ED of all ages; up to 80% will respond with a good erection. Only a positive penile response has diagnostic significance. The positive results reduce the necessity for further invasive investigations.