Can an in-person hands-on applicator-based teaching session improve trainee knowledge and comfort with complex gynecologic brachytherapy?

INTRODUCTION: With the emergence of imaged-based planning and hybrid applicators the complexity of gynecologic brachytherapy has dramatically increased. Despite the known advantages of brachytherapy, notable national declines in utilization of brachytherapy have been documented. Clearly improved education in the sphere of gynecologic brachytherapy is needed. We hypothesize that a hands-on applicator-based training session would improve trainee comfort with gynecologic brachytherapy. METHODS AND MATERIALS: An in-person, applicator-based, hands-on training session was held with trainees from both radiation and gynecologic oncology programs. Trainees practiced assembling and handling applicators while receiving instruction on clinical scenarios in which various applicators are used in gynecologic cancer brachytherapy. Pre- and post-session, participants were administered an objective test of 10 pictorial-based case vignettes to quantify ability to select the correct applicator based on the interpretation of T2-weighted MR images. Participants additionally received a subjective survey to quantify comfort and experience with gynecologic brachytherapy using Likert-type question formatting. RESULTS: A total of 14 trainees participated. Most common case volume experience was 0-10 intracavitary (57%), 0-10 hybrid (71%), and 0-10 interstitial (71%). Pre-session, the most common answer to comfort level was "not comfortable still learning" for all brachytherapy types, and most common answer to largest gap in knowledge was all facets of brachytherapy. Average case-based test score was 3.5/10 pre-session versus 5.3/10 post-session (p = 0.028). Post-session, all respondents reported improved comfort level with brachytherapy. Post-session, most common answer to largest gap in knowledge was applicator/patient selection, and applicator/patient selection was also the largest area of identified improvement. 100% of participants felt repeating the session in the future would be helpful. CONCLUSIONS: Hands-on training with applicators improves both subjective and objective comfort with gynecologic brachytherapy. With 100% of participants requesting to implement this session into resident training, we suggest national opportunities might exist to expand educational processes and improve utilization of complex gynecologic brachytherapy in practice.

Redefining bladder neck dose in low-dose-rate prostate brachytherapy-Can we improve urinary toxicity without impacting disease control?

BACKGROUND: We sought to assess the impact of bladder neck dose (BND) on patient reported urinary toxicity, and feasibility of relative urethral sparing technique in prostate brachytherapy (PB). METHODS AND MATERIALS: We retrospectively identified bladder neck as a point dose on post-implant CT scans in patients treated with 131Cs PB. Urinary symptoms were assessed through EPIC questionnaires. Patient cohorts were identified based on mean BND as a percentage of prescription dose with toxicity assessment at each time point. RESULTS: In our cohort of 542 patients, BND was associated with clinically significant acute urinary symptoms and chronic symptoms, as patients receiving >70% of the prescription dose had significantly worse overall EPIC scores than patients receiving ≤70% of prescription dose. There was no difference in bDFS between patients receiving BND ≤70% (96% bDFS) and >70% (94% bDFS) at a median follow up of 57 months. CONCLUSIONS: BND has a significant impact on both acute and chronic urinary symptoms, with reduced symptoms reported with BND <70% of prescription dose. With a median follow up of 4.7 years, excellent bDFS has thus far been achieved with relative urethral and bladder neck sparing. Utilizing this constraint should improve urinary symptoms without impacting disease control.

Cs-131 prostate brachytherapy boost and effect of hydrogel rectal spacer on long-term patient-reported rectal bleeding and bowel quality of life.

PURPOSE: This study evaluates long-term patient-reported bowel quality of life (QOL), rectal bleeding, and bleeding bother in patients with prostate cancer treated with external beam radiation therapy (EBRT) and Cesium-131 LDR brachytherapy (LDR-BT) boost with and without hydrogel rectal spacer. METHODS AND MATERIALS: This is a retrospective analysis of prostate cancer patients treated between 2007 and 2022 with 45 Gy EBRT followed by 85 Gy Cs-131 LDR-BT boost with or without hydrogel rectal spacer. Expanded Prostate Cancer Index Composite (EPIC) QOL questionnaires pre-treatment and at each follow-up were collected. Patient-reported rectal bleeding occurring more than "rarely" and bother from rectal bleeding occurring more than a "very small problem" were deemed clinically significant. Fisher's exact test was used to test the association of rectal spacer use and the incidence of clinically significant rectal bleeding and bleeding bother. Paired samples t-test was used to analyze mean bowel scores at each time point. RESULTS: Three hundred and forty-one patients were included in the analysis. The rectal spacer was used in 108 patients. Overall median follow-up was 48 months (IQR, 24-72), with a median follow-up of 24 months (IQR, 12-37.5) for the hydrogel group and 60 months (IQR, 36-84) for the non-hydrogel group. EPIC questionnaire response rates at median follow-up were 33% and 37% for the hydrogel and non-hydrogel groups, respectively. A clinically significant decrease in mean bowel domain scores was seen in the bowel bother domain at 6 and 12 months for patients who did not receive a rectal spacer. At the last follow-up of 60 months, the prevalence of clinically significant rectal bleeding and bleeding bother were 2.2% and 2.2%, respectively. The cumulative incidence of clinically significant long-term rectal bleeding was 2.8% and 18.9% in the hydrogel group and non-hydrogel group, respectively (Fisher's exact test, p < 0.0001). The cumulative incidence of clinically significant long-term bowel bother was 4.6% and 19.7% in the hydrogel group and non-hydrogel group, respectively (Fisher's exact test, p < 0.001). CONCLUSIONS: Use of hydrogel rectal spacer with EBRT and Cs-131 LDR-BT boost was significantly associated with a lower incidence of patient-reported rectal bleeding and bother from rectal bleeding, and better long-term bowel QOL. Cumulative incidence was 2.8% (hydrogel group) versus 18.9% (non-hydrogel group) and 4.6% (hydrogel group) versus 19.7% (non-hydrogel group) for clinically significant long-term rectal bleeding and long-term bleeding bother, respectively.

Do patients with Peyronie's disease perceive penile curvature in adults and children differently than the general population?

BACKGROUND: As perception of penile curvature varies widely, we sought to understand how adults perceive curvature and how these opinions compare with those of patients with curvature, specifically Peyronie's disease (PD). AIM: To investigate the perspectives of curvature correction from adults with and without PD, as well as differences within demographics. METHODS: A cross-sectional survey was administered to adult patients and nonpatient companions in general urology clinics at 3 institutions across the United States. Men, women, and nonbinary participants were recruited. Patients were grouped as having PD vs andrology conditions without PD vs general urology conditions plus companions. The survey consisted of unlabeled 2-dimensional images of penis models with varying degrees of curvature. Participants selected images that they would want surgically corrected for themselves and their children. Univariable and multivariable analyses were performed to identify demographic variables associated with willingness to correct. OUTCOMES: Our main outcome was to detect differences in threshold to correct curvature between those with and without PD. RESULTS: Participants were grouped as follows: PD (n = 141), andrology (n = 132), and general (n = 302) . Respectively, 12.8%, 18.9%, and 19.9% chose not to surgically correct any degree of curvature (P = .17). For those who chose surgical correction, the mean threshold for correction was 49.7°, 51.0°, and 51.0° (P = .48); for their children, the decision not to correct any degree of curvature was 21.3%, 25.4%, and 29.3% (P = .34), which was significantly higher than correction for themselves (P < .001). The mean threshold for their children's correction was 47.7°, 53.3°, and 49.4° for the PD, andrology, and general groups (P = .53), with thresholds no different vs themselves (P = .93). On multivariable analysis, no differences were seen in demographics within the PD and andrology groups. In the general group, participants aged 45 to 54 years and those who identified as LGBTQ (lesbian, gay, bisexual, transgender, queer) had a higher threshold for correction as compared with their counterparts when factoring other demographic variables (63.2° vs 48.8°, P = .001; 62.1° vs 50.4°, P = .05). CLINICAL IMPLICATIONS: With changing times and viewpoints, this study stresses the importance of shared decision making and balancing risks and benefits to correction of penile curvature. STRENGTHS AND LIMITATIONS: Strengths include the broad population surveyed. Limitations include the use of artificial models. CONCLUSION: No significant differences were seen in the decision to surgically correct curvature between participants with and without PD, with participants being less likely to choose surgical correction for their children.

A narrative review of pelvic floor muscle training in the management of incontinence following prostate treatment.

Background and Objective: Urinary incontinence following prostate treatment (IPT) is a common complication with corresponding negative impacts on quality of life. Pelvic floor muscle training (PFMT) is a non-invasive treatment strategy to treat combat this clinical issue, and has been recognized by medical associations globally and increasingly supported by large bodies of literature. Accordingly, many studies demonstrate a significant benefit of pelvic floor muscle training to continence status and quality of life in men with incontinence following prostate treatment. However, related research is limited by variety in treatment regimens, outcome measures, and study designs, with unclear impact on treatment success. We aim to provide a brief overview of pathology and incidence of incontinence following prostate surgery and an understanding how PFMT is currently used to treat and prevent this clinical consequence. Methods: A comprehensive literature search was conducted utilizing PubMed, Medline, and Google Scholar. Search criteria included systematic reviews and randomized control trials published in the year 2000 to present. References of resulting studies were further analyzed to identify further articles of relevance. Keywords searched included: "post-prostatectomy incontinence", "pelvic muscle strengthening", "Benign Prostatic Hyperplasia", and "pelvic floor muscle training". Peer-reviewed publications that demonstrated a novel addition to the existing body of literature on this subject were included. Key Content and Findings: Upon review of the current research landscape, PFMT is largely supported in treatment of IPT. Analysis of current literature on this subject demonstrates heterogeneity in protocols, measures of treatment success, and patient numbers. Nevertheless, benefits to continence and quality of life are noted across an expansive body of literature and as such, PFMT is therefore recommended as an important part of the treatment algorithm following radical prostatectomy. Conclusions: PFMT is an important and effective part of the treatment algorithm in the prevention and treatment of IPT. Additional research is needed to more extensively assess PFMT's role in treating this clinical consequence, especially following other prostate surgeries.

Effect of short-term corticosteroid usage on acute urinary toxicity following Cs-131 prostate brachytherapy.

PURPOSE: To evaluate short-term patient reported urinary quality of life scores in patients with prostate cancer treated at our institution with and without perioperative prednisone following Cesium-131 (131Cs) prostate LDR brachytherapy. METHODS AND MATERIALS: We started routinely using a perioperative 7-day course of prednisone at a dose of 5 mg per day, beginning 1 day prior to 131Cs prostate LDR brachytherapy from 2013 with goal of improving acute urinary symptomatology. One hundred consecutive patients treated with prednisone were selected, with comparison to 100 consecutive patients who were not treated with prednisone. We analyzed for differences in mean change with standard deviation (SD) in EPIC and AUA scores at 0.5-1 month and 3 months with or without prednisone by Mann-Whitney U Test. Binary logistic regression was performed to assess for impact of prednisone on postoperative urinary catheter use. RESULTS: Pretreatment EPIC and AUA scores were available in 197 patients. Less reduction in EPIC US score was noted at 0.5-1.0 month in the group who received prednisone with mean change of -22.9 (SD 15.4) when compared to the group who did not receive prednisone with mean change of -31.7 (SD 19.3), p < 0.01, with significance lost at 3 months. There was no significant difference in acute urinary retention requiring postoperative urinary catheter placement with perioperative prednisone (OR 1.13, p = 0.71). CONCLUSIONS: A short course of perioperative low-dose prednisone was associated with less severe worsening in urinary symptoms by the EPIC questionnaire at the 0.5-1.0-month timepoint suggesting some improvement in acute urinary quality of life, although differences did not remain statistically significant at 3 months.

Treatment of intermediate-risk prostate cancer with Cs-131: Long-term results from a single institution.

PURPOSE: To evaluate our institutional outcomes utilizing Cs-131 prostate brachytherapy (PB) for the intermediate-risk (IR) group of prostate cancer patients. METHODS AND MATERIALS: We reviewed a prospectively collected database of men treated with Cs-131 PB between 2006 and 2019. Patients with less than 24-months follow-up were excluded. Patients were classified as IR if they had one of the following factors: Gleason Score 7, prostate specific antigen >10 but <20 ng/mL, or T2b-c on clinical exam. We defined unfavorable-IR (UIR) as having either Grade Group 3, >1 IR factors, or ≥50% positive core biopsies. The Kaplan-Meier method was used to estimate actuarial event-time probabilities for biochemical freedom from disease (BFD). RESULTS: A total of 335 patients with a median follow-up of 70.1 months (IQR 48.3-106.3 months) were identified. Androgen deprivation therapy (ADT) was used in 7.2% of patients. Favorable-IR (FIR) patients were commonly treated with PB alone (91.8%). FIR patients who underwent PB alone had a 5-year BFD of 98.1%. UIR patients were commonly treated with external beam radiotherapy plus PB (61.2%). These patients had 5-year BFD of 91.1%. The 5-year BFD for UIR patients treated without ADT was 90.9%, whereas it was 95.0% among UIR patients treated with ADT (log-rank p = 0.83). CONCLUSIONS: FIR patients have excellent outcomes when treated with PB alone. External beam radiotherapy plus PB is a reasonable treatment approach for UIR patients. Future studies may elucidate which IR patients would benefit from treatment intensification.

Intraprostatic calcification and biochemical recurrence in men treated with cesium-131 prostate brachytherapy.

PURPOSE: Baseline intraprostatic calcification (IC) has been shown to be associated with a higher rate of biochemical recurrence (BCR) in men treated with iodine-125 prostate brachytherapy (PB). We evaluated this association in a cohort of men treated with cesium-131 PB. METHODS AND MATERIALS: We retrospectively reviewed the charts of all low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- external beam radiotherapy (EBRT) at our institution from 2/2011 to 7/2018. Patients with < 24 months of follow up or those who received androgen deprivation therapy were excluded. Baseline IC status (defined as one or more ICs ≥ 5 mm) was determined on post-PB CT scans. Cox analysis was used to assess predictors of BCR and Kaplan-Meier survival curves were calculated. RESULTS: Two hundred and sixteen low- and intermediate-risk prostate cancer patients treated with cesium-131 PB +/- EBRT were included. Median follow up was 56.9 months (range 24.1-111.4). Overall, 76 (35.2%) patients had baseline IC and 140 (64.8%) did not. Baseline disease characteristics did not differ significantly between groups. On univariate Cox analysis, only risk group (p = 0.047) and initial PSA (p = 0.016) were significant predictors of BCR, whereas baseline IC was not (p = 0.11). The 5-year BCR-free survival in patients with versus without baseline IC was 97.7% versus 93.8% (p = 0.405), respectively. CONCLUSIONS: In a cohort of low- and intermediate-risk prostate cancer patients treated with cesium-131 PB, the rate of BCR in men with baseline IC was low and baseline IC was not associated with a higher risk of BCR.

Hypofractionated Prostate Radiation Therapy: Adoption and Dosimetric Adherence Through Clinical Pathways in an Integrated Oncology Network.

PURPOSE: Updates to consensus guidelines in October 2018 recommending moderately hypofractionated external beam radiotherapy (mHF-EBRT) in prostate cancer lagged several years after publication of evidence supporting its efficacy. In January 2018, we amended our prostate cancer clinical pathway (CP) to facilitate adoption of mHF-EBRT. Herein, we analyze patterns of care and changes in mHF-EBRT use after the CP modification. METHODS: Our prostate CP was amended in January 2018 to make mHF-EBRT the recommended treatment for patients with low- and intermediate-risk prostate cancer pursuing curative EBRT monotherapy. Normal-tissue dose constraints accompanied the CP modification to guide planning. Use of mHF-EBRT from 2015 to 2017 was compared with use in 2018 after the CP modification, using the Cochran-Armitage test for trend. Predictors of mHF-EBRT use and adherence to dose constraints were analyzed with binary logistic regression. RESULTS: In 560 patients treated with EBRT monotherapy, mHF-EBRT use increased from 3.7% in 2015-2017 to 85.6% in 2018 (P < .001), whereas conventionally fractionated EBRT (CF-EBRT) use decreased from 96.3% to 14.4% (P < .001). Consultation year of 2018 (odds ratio [OR], 214.6; 95% CI, 94.5 to 484.6; P < .001), treatment at an academic facility (OR, 4.5; 95% CI, 1.8 to 11.3; P = 0.001), and having a smaller prostate (OR, 0.99; 95% CI, 0.97 to 1.00; P = .028) predicted for mHF-EBRT use. At least five of six recommended bladder and rectal dose constraints were met in 89.4% of patients. CONCLUSION: Modification of our prostate cancer CP, in concert with institutional policies to monitor and audit CP compliance, facilitated rapid adoption of mHF-EBRT in our large, integrated cancer center with good adherence to dosimetric constraints.

Acute patient-reported bowel quality of life and rectal bleeding with the combination of prostate external beam radiation, low-dose-rate brachytherapy boost, and SpaceOAR.

PURPOSE: This study evaluates acute patient-reported bowel quality of life (QOL) and rectal bleeding in prostate cancer patients treated with combination external beam radiation (EBRT), low-dose-rate brachytherapy (LDR-BT), and SpaceOAR. MATERIALS AND METHODS: A retrospective review of prostate cancer patients treated with EBRT (45 Gy), cesium-131 LDR-BT (85 Gy), and SpaceOAR was conducted. Patient-reported acute (≤3 months after LDR-BT) bowel QOL and rectal bleeding was analyzed from Expanded Prostate Cancer Index Composite (EPIC) questionnaires. Five-point changes in mean bowel QOL scores were considered clinically significant. Clinically significant rectal bleeding was bleeding occurring more than "rarely" ("about half the time," "usually," or "always"), and clinically significant bleeding bother was considering bleeding a "small, moderate, or big problem." Outcomes were analyzed using descriptive statistics and paired t-tests. RESULTS: 69 patients were identified. Bowel summary, function, and bother scores clinically and significantly decreased 2 weeks after LDR-BT (79.9 ± 15.6, 80.5 ± 15.4, and 79.4 ± 18.1, respectively) compared with pre-EBRT scores (92.3 ± 9.1, 93.3 ± 9.0, and 92.6 ± 11.9, respectively) and pre-LDR-BT scores (91.1 ± 11.0, 91.6 ± 9.8, and 90.6 ± 13.3, respectively), but returned to clinical and statistical baseline pre-EBRT values at 3 months (88.7 ± 12.4, 88.8 ± 11.1, and 88.7 ± 14.5, respectively). The 3-month cumulative incidence of clinically significant rectal bleeding and bleeding bother was 4.35% and 2.90%, respectively. CONCLUSIONS: With combination EBRT, LDR-BT, and SpaceOAR, bowel QOL returned to the baseline 3 months after LDR-BT. Clinically significant rectal bleeding was <5%. Further followup will confirm if low acute rectal toxicity translates to reduced late toxicity.

Cesium-131 prostate brachytherapy: A single institutional long-term experience.

AIMS: To report on the PSA outcomes in men undergoing prostate seed implant (PSI) with Cesium-131 at a single institution. MATERIALS AND METHODS: All patients who underwent prostate brachytherapy with Cesium-131 (131Cs) at our institution and had the potential for at least 24 months of follow up were included in this study. Results are reported for the by NCCN risk group (low, low/high-intermediate, and high), as well as by treatment received (monotherapy, combination external beam radiation + PSI, or trimodal therapy with androgen deprivation). The Phoenix definition (absolute nadir plus 2 ng/mL) was used to define biochemical freedom from disease (BFD). RESULTS: Eight hundred and six men have undergone prostate brachytherapy with Cesium-131 at our institution, and 669 men were included in analysis. Median follow up was 60.0 months (range: 0-144 months). According to NCCN risk categories, 29.9% were low-, 55.6% intermediate-, and 14.5% high-risk. Using the Phoenix criteria, 5/10-year BFD was 97.1/95.3% for patients in the low-risk category, 94.0/90.1% for patients in the intermediate-risk category, and 86.2/56.6% for patients in the high-risk category. PSA ≤0.2 ng/dL at 4 years was predictive of 10 year biochemical control: 96.3% vs 70.4%, p < 0.001. CONCLUSIONS: The present study demonstrates that prostate brachytherapy with 131Cs achieves excellent long-term biochemical control.

Non-testosterone management of male hypogonadism: an examination of the existing literature.

Testosterone deficiency is defined as a total testosterone level <300 ng/dL confirmed on two early morning lab draws. Testosterone therapy has historically been offered to men with symptomatic testosterone deficiency in the form of injections, gels, or pellets. However, these treatments are invasive or have undesirable effects including the risk of drug transference. Additionally, testosterone therapy has been associated with increases in hematocrit and controversy remains regarding the risk of cardiovascular and thromboembolic events while on testosterone therapy. As such, much interest has recently been focused on alternative treatment options for testosterone deficiency in the form of orally-administered medications with more favorable side effect profiles. Lifestyle modifications and varicocelectomy have been shown to raise endogenous testosterone production. Similarly, SERMs and aromatase inhibitors (AIs) have been shown to raise testosterone levels safely and effectively. Human chorionic gonadotropin (hCG) remains the only FDA-approved non-testosterone treatment option for testosterone deficiency in men. However, this medication is expensive and requires patient-administered injections. Over the counter herbal supplements and designer steroids remain available though they are poorly studied and are associated with the potential for abuse as well as increased hepatic and cardiovascular risks. This review aims to discuss the existing treatment alternatives to traditional testosterone therapy, including efficacy, safety, and side effects of these options. The authors suggest that the SERM clomiphene citrate (CC) holds the greatest promise as a non-testosterone treatment option for testosterone deficiency.

Impact of environmental toxin exposure on male fertility potential.

Idiopathic infertility is the most common individual diagnosis in male infertility, representing nearly 44% of cases. Research studies dating over the last half-century consistently demonstrate a decline in male fertility that is incompletely explained by obesity, known genetic causes, or diet and lifestyle changes alone. Human exposures have changed dramatically over the same time course as this fertility decline. Synthetic chemicals surround us. Some are benevolent; however, many are known to cause disruption of the hypothalamic-pituitary-gonadal axis and impair spermatogenesis. More than 80,000 chemicals are registered with the United States National Toxicology Program and nearly 2,000 new chemicals are introduced each year. Many of these are known toxins, such as phthalates, polycyclic aromatic hydrocarbons, aromatic amines, and organophosphate esters, and have been banned or significantly restricted by other countries as they carry known carcinogenic effects and are reproductively toxic. In the United States, many of these chemicals are still permissible in exposure levels known to cause reproductive harm. This contrasts to other chemical regulatory legislature, such as the European Union's REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) regulations which are more comprehensive and restrictive. Quantification of these diverse exposures on an individual level has proven challenging, although forthcoming technologies may soon make this data available to consumers. Establishing causality and the proportion of idiopathic infertility attributable to environmental toxin exposures remains elusive, however, continued investigation, avoidance of exposure, and mitigation of risk is essential to our reproductive health. The aim of this review is to examine the literature linking changes in male fertility to some of the most common environmental exposures. Specifically, pesticides and herbicides such as dichlorodiphenyltrichloroethane (DDT), dibromochloropropane (DBCP), organophosphates and atrazine, endocrine disrupting compounds including plastic compounds phthalates and bisphenol A (BPA), heavy metals, natural gas/oil, non-ionizing radiation, air and noise pollution, lifestyle factors including diet, obesity, caffeine use, smoking, alcohol and drug use, as well as commonly prescribed medications will be discussed.

Phosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization.

Fertilization is essential for species survival. Although Izumo1 and Juno are critical for initial interaction between gametes, additional molecules necessary for sperm:egg fusion on both the sperm and the oocyte remain to be defined. Here, we show that phosphatidylserine (PtdSer) is exposed on the head region of viable and motile sperm, with PtdSer exposure progressively increasing during sperm transit through the epididymis. Functionally, masking phosphatidylserine on sperm via three different approaches inhibits fertilization. On the oocyte, phosphatidylserine recognition receptors BAI1, CD36, Tim-4, and Mer-TK contribute to fertilization. Further, oocytes lacking the cytoplasmic ELMO1, or functional disruption of RAC1 (both of which signal downstream of BAI1/BAI3), also affect sperm entry into oocytes. Intriguingly, mammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts. Collectively, these data identify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players in sperm:egg fusion.

Long-Term Safety and Efficacy of Clomiphene Citrate for the Treatment of Hypogonadism.

PURPOSE: Clomiphene citrate may be used as an off label treatment of hypogonadism. There are few long-term data on clomiphene citrate efficacy and safety when administered for more than 3 years. We assessed improvements in testosterone and hypogonadal symptoms while on clomiphene citrate for extended periods. MATERIALS AND METHODS: We performed a retrospective review to identify patients treated with clomiphene citrate for hypogonadism (baseline testosterone less than 300 ng/dl) at a total of 2 institutions from 2010 to 2018. We assessed the duration of clomiphene citrate therapy, serum testosterone levels, symptom improvement and clomiphene citrate side effects. RESULTS: A total of 400 patients underwent clomiphene citrate treatment for a mean ± SD of 25.5 ± 20.48 months (range 0 to 84). Of the patients 280 received clomiphene citrate for 3 years or less (mean 12.75 ± 9.52 months) and 120 received it for more than 3 years (mean 51.93 ± 10.52 months). Of men on clomiphene citrate for more than 3 years 88% achieved eugonadism, 77% reported improved symptoms and 8% reported side effects. Estradiol was significantly increased following clomiphene citrate treatment. Results did not significantly differ between patients treated for more than 3, or 3 or fewer years. The most common side effects reported by patients treated more than 3 years included changes in mood in 5, blurred vision in 3 and breast tenderness in 2. There was no significant adverse event in any patient treated with clomiphene citrate. CONCLUSIONS: Clomiphene citrate is not typically offered as primary treatment of hypogonadism in men who do not desire fertility preservation. These data demonstrate that clomiphene citrate is safe and effective with few side effects when used as long-term treatment of hypogonadism.

Long-Term Patient-Reported Rectal Bleeding and Bowel-Related Quality of Life After Cs-131 Prostate Brachytherapy.

PURPOSE: There is limited long-term data on outcome and side effects of Cs-131 prostate brachytherapy and minimal patient-reported data on rectal bleeding with any isotope. We aimed to describe the incidence, prevalence, and predictors of late patient-reported rectal bleeding after Cs-131 brachytherapy. METHODS AND MATERIALS: We reviewed a prospectively collected database of 620 men treated with Cs-131 prostate brachytherapy. Of 620 patients, 390 (62.9%) received brachytherapy as monotherapy; the remainder received combination therapy with external beam radiation therapy (EBRT). Patients were administered Expanded Prostate Cancer Index Composite questionnaires preoperatively and postoperatively at each follow-up visit. The primary outcome was late rectal bleeding, defined as rectal bleeding reported at the 6-month follow-up or later. Clinically significant rectal bleeding was defined as occurring more than "rarely," and clinically significant bother from rectal bleeding was defined as considering bleeding more than a "very small problem." Univariate and multivariate Cox regression were performed to identify factors predictive for rectal bleeding. RESULTS: With a median follow-up time of 48 months, the cumulative incidence of clinically significant late rectal bleeding was 12.4%, with 15.2% reporting clinically significant bother from bleeding. At the time of last follow-up, the prevalence of clinically significant rectal bleeding and bother were 4.0% and 4.7%, respectively. On univariate analysis, acute clinically significant rectal bleeding, defined as occurring within the first 6 months (P = .001) and combination therapy with EBRT (P = .001) predicted for clinically significant late rectal bleeding. On multivariate analysis, both EBRT (P = .001; hazard ratio, 2.50; 95% confidence interval, 1.58-3.94) and acute rectal bleeding (P < .001; hazard ratio, 3.11; 95% confidence interval, 1.75-5.53) remained significant predictors for late rectal bleeding. CONCLUSIONS: Prostate brachytherapy with Cs-131 is well tolerated in the long term. Although the incidence of clinically significant patient-reported late rectal bleeding was 12.4%, the prevalence at last follow-up was only 4.0%, suggesting that this problem tends to resolve.

Phase 2 Study of Radiation Therapy Plus Low-Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420.

PURPOSE: To evaluate the toxicity and efficacy of adjuvant temozolomide (TMZ) and irinotecan (CPT-11) for 12 months after concurrent chemoradiation in patients with newly diagnosed glioblastoma (GBM). METHODS AND MATERIALS: Trial RTOG 04-20, a single-arm, multi-institutional phase 2 trial, was designed to determine the efficacy and toxicity of concomitant TMZ and radiation therapy (RT) followed by adjuvant TMZ combined with CPT-11 given for 12 cycles compared with historical controls of adjuvant TMZ alone given for 6 cycles. RESULTS: A total of 170 patients were enrolled, 152 of whom were eligible. Adjuvant CPT-11 combined with TMZ was more toxic than expected. A higher rate of hematologic and gastrointestinal toxicities was more frequently noted with the combination regimen compared with adjuvant TMZ alone. Grade 3/4 hematologic toxicity was 38% compared with 14% reported in the Stupp trial. After an early interim analysis, the adjuvant CPT-11 dose was reduced to 100 mg/m2 on days 1 and 5 for the first cycle. CPT-11 dose escalation proceeded over the first 3 cycles if tolerated. Median overall survival for all eligible patients was 16.9 months compared with 13.7 months of the historical control (P = .03). Post hoc subgroup analysis suggested an improvement in overall survival for patients with Radiation Therapy Oncology Group recursive partitioning analysis class 3, although improvement was limited to 22 patients (14% of eligible patients). CONCLUSIONS: Although irinotecan and TMZ for 12 cycles given after chemoradiation for patients with newly diagnosed glioblastoma significantly improved median survival compared with historical control data at the time the study was conducted, the historical control median survival time of 13.7 months does not represent the current benchmark for this patient population. Treatment intensification does prolong overall survival compared with the current standard.

Clomiphene Citrate for the Treatment of Hypogonadism.

INTRODUCTION: Clomiphene citrate (CC) is a selective estrogen receptor modulator that has been used for the treatment of hypogonadism in men since the 1970s. It acts centrally to increase secretion of luteinizing hormone and follicle-stimulating hormone, thereby increasing testosterone production and serum levels. Unlike testosterone replacement therapy, CC does not suppress the hypothalamic-pituitary-gonadal axis, preserving intratesticular testosterone production and spermatogenesis. This is especially useful in treating hypogonadal men who are interested in fertility. AIM: To review the literature regarding the use of CC in the setting of hypogonadism. METHODS: A review of the relevant literature through September 2018 was performed via PubMed. MAIN OUTCOME MEASURE: The data regarding the efficacy and safety of CC when used in the setting of hypogonadism is summarized. RESULTS: Although results are mixed, many studies show CC reduces symptoms in hypogonadal men. Studies have also shown improvement in erectile function and bone mineral density, as well as a reduction in body mass index. There have been few studies investigating fertility rates in hypogonadal men treated with CC, but a metaanalysis of these shows significant improvement in fertility rates. Several studies show improvement in semen parameters. Few studies have investigated adverse effects of the drug. Reports include headache, dizziness, gynecomastia, and exacerbation of psychiatric illnesses. Despite these reports, CC is generally considered to be safe and well tolerated. CONCLUSION: CC is safe and effective and should remain in the armament of urologists treating hypogonadal men, especially men interested in preservation of fertility. Wheeler KM, Sharma D, Kavoussi PK, et al. Clomiphene citrate for the treatment of hypogonadism. Sex Med Rev 2019;7:272-276.