Noninferiority of Hypofractionated vs Conventional Postprostatectomy Radiotherapy for Genitourinary and Gastrointestinal Symptoms: The NRG-GU003 Phase 3 Randomized Clinical Trial.

Importance: No prior trial has compared hypofractionated postprostatectomy radiotherapy (HYPORT) to conventionally fractionated postprostatectomy (COPORT) in patients primarily treated with prostatectomy. Objective: To determine if HYPORT is noninferior to COPORT for patient-reported genitourinary (GU) and gastrointestinal (GI) symptoms at 2 years. Design, Setting, and Participants: In this phase 3 randomized clinical trial, patients with a detectable prostate-specific antigen (PSA; ≥0.1 ng/mL) postprostatectomy with pT2/3pNX/0 disease or an undetectable PSA (<0.1 ng/mL) with either pT3 disease or pT2 disease with a positive surgical margin were recruited from 93 academic, community-based, and tertiary medical sites in the US and Canada. Between June 2017 and July 2018, a total of 296 patients were randomized. Data were analyzed in December 2020, with additional analyses occurring after as needed. Intervention: Patients were randomized to receive 62.5 Gy in 25 fractions (HYPORT) or 66.6 Gy in 37 fractions (COPORT). Main Outcomes and Measures: The coprimary end points were the 2-year change in score from baseline for the bowel and urinary domains of the Expanded Prostate Cancer Composite Index questionnaire. Secondary objectives were to compare between arms freedom from biochemical failure, time to progression, local failure, regional failure, salvage therapy, distant metastasis, prostate cancer-specific survival, overall survival, and adverse events. Results: Of the 296 patients randomized (median [range] age, 65 [44-81] years; 100% male), 144 received HYPORT and 152 received COPORT. At the end of RT, the mean GU change scores among those in the HYPORT and COPORT arms were neither clinically significant nor different in statistical significance and remained so at 6 and 12 months. The mean (SD) GI change scores for HYPORT and COPORT were both clinically significant and different in statistical significance at the end of RT (-15.52 [18.43] and -7.06 [12.78], respectively; P < .001). However, the clinically and statistically significant differences in HYPORT and COPORT mean GI change scores were resolved at 6 and 12 months. The 24-month differences in mean GU and GI change scores for HYPORT were noninferior to COPORT using noninferiority margins of -5 and -6, respectively, rejecting the null hypothesis of inferiority (mean [SD] GU score: HYPORT, -5.01 [15.10] and COPORT, -4.07 [14.67]; P = .005; mean [SD] GI score: HYPORT, -4.17 [10.97] and COPORT, -1.41 [8.32]; P = .02). With a median follow-up for censored patients of 2.1 years, there was no difference between HYPORT vs COPORT for biochemical failure, defined as a PSA of 0.4 ng/mL or higher and rising (2-year rate, 12% vs 8%; P = .28). Conclusions and Relevance: In this randomized clinical trial, HYPORT was associated with greater patient-reported GI toxic effects compared with COPORT at the completion of RT, but both groups recovered to baseline levels within 6 months. At 2 years, HYPORT was noninferior to COPORT in terms of patient-reported GU or GI toxic effects. HYPORT is a new acceptable practice standard for patients receiving postprostatectomy radiotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT03274687.

Stereotactic body radiation therapy for Japanese patients with localized prostate cancer: 2-year results and predictive factors for acute genitourinary toxicities.

OBJECTIVE: We aimed to report the 2-year results of stereotactic body radiation therapy for prostate cancer and identify the clinical and dosimetric factors that predict acute genitourinary toxicities. METHODS: We retrospectively reviewed the medical records of patients with non-metastatic prostate cancer treated at Toyota Memorial Hospital between 2017 and 2020. The patients were treated with stereotactic body radiation therapy with a total dose of 36.25 Gy in five fractions on consecutive weekdays. While low-risk patients received radiotherapy alone, intermediate- to high-risk patients also received androgen deprivation therapy. RESULTS: We analysed a total of 104 patients, including 10, 60 and 34 low-, intermediate- and high-risk patients, respectively. The median follow-up duration was 2 years. We did not observe biochemical/clinical recurrence, distant metastasis or death from prostate cancer. One patient died of another cause. Grade 2 acute genitourinary toxicity was observed in 40 (38%) patients. Age (P = 0.021), genitourinary toxicity of grade ≥1 at baseline (P = 0.023) and bladder mean dose (P = 0.047) were significantly associated with the incidence of grade 2 acute genitourinary toxicity. The cut-off value of 65 years for age and 10.3 Gy for the bladder mean dose were considered the most appropriate. Grade 2 acute gastrointestinal toxicity was observed in five (5%) patients. None of the patients experienced grade ≥3 acute or late toxicity. CONCLUSIONS: Stereotactic body radiation therapy is feasible for Japanese patients with prostate cancer, with acceptable acute toxicity. Age, genitourinary toxicity at baseline and bladder mean dose predict grade 2 acute genitourinary toxicity.

Genitourinary Emergencies in Older Adults.

Older adults are frequently seen in the emergency department for genitourinary complaints, necessitating that emergency physicians are adept at managing a myriad of genitourinary emergencies. Geriatric patients may present with acute kidney injury, hematuria, or a urinary infection and aspects of how managing these presentations differs from their younger counterparts is emphasized. Older adults may also present with acute urinary retention or urinary incontinence as a result of genitourinary pathology or other systemic etiologies. Finally, genital complaints as they pertain to older adults are briefly highlighted with emphasis on emergent management and appropriate referrals.

Urogenital function following robotic and laparoscopic rectal cancer surgery: meta-analysis.

BACKGROUND: Mixed results are reported on clinical and cancer outcomes in laparoscopic rectal cancer surgery (LRCS) compared with robotic rectal cancer surgery (RRCS). However, more favourable functional outcomes are reported following RRCS. This study compared urinary and sexual function following RRCS and LRCS in male and female patients. METHODS: A systematic review and meta-analysis of urinary and sexual function after RRCS and LRCS was performed following PRISMA and MOOSE guidelines, and registered prospectively with PROSPERO (ID:CRD42020164285). The functional outcome reporting tools most commonly included: the International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI). Mean scores and changes in mean scores from baseline were analysed using RevMan version 5.3. RESULTS: Ten studies were included reporting on 1286 patients. Some 672 patients underwent LRCS, of whom 380 (56.5 per cent) were men and 116 (17.3 per cent) were women (gender not specified in 176 patients, 26.2 per cent). A total of 614 patients underwent RRCS, of whom 356 (58.0 per cent) were men and 83 (13.5 per cent) were women (gender not specified in 175 patients, 28.5 per cent). Regarding urinary function in men at 6 months after surgery, IPSS scores were significantly better in the RRCS group than in the LRCS group (mean difference (MD) -1.36, 95 per cent c.i. -2.31 to -0.40; P = 0.005), a trend that persisted at 12 months (MD -1.08, -1.85 to -0.30; P = 0.007). ΔIIEF scores significantly favoured RRCS at 6 months [MD -3.11 (95%CI -5.77, -0.44) P <0.021] and 12 months [MD -2.76 (95%CI -3.63, -1.88) P <0.001] post-operatively. Mixed urinary and sexual function outcomes were reported for women. CONCLUSION: This meta-analysis identified more favourable urinary and erectile function in men who undergo robotic compared with conventional laparoscopic surgery for rectal cancer. Outcomes in women did not identify a consistently more favourable outcome in either group. As robotic rectal cancer surgery may offer more favourable functional outcomes it should be considered and discussed with patients.

Adjuvant radiotherapy versus early salvage radiotherapy following radical prostatectomy (TROG 08.03/ANZUP RAVES): a randomised, controlled, phase 3, non-inferiority trial.

BACKGROUND: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy. METHODS: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652. FINDINGS: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]). INTERPRETATION: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity. FUNDING: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia.

Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localised prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial.

BACKGROUND: Adjuvant radiotherapy reduces the risk of biochemical progression in prostate cancer patients after radical prostatectomy. We aimed to compare adjuvant versus early salvage radiotherapy after radical prostatectomy, combined with short-term hormonal therapy, in terms of oncological outcomes and tolerance. METHODS: GETUG-AFU 17 was a randomised, open-label, multicentre, phase 3 trial done at 46 French hospitals. Men aged at least 18 years who had an Eastern Cooperative Oncology Group performance status of 1 or less, localised adenocarcinoma of the prostate treated with radical prostatectomy, who had pathologically-staged pT3a, pT3b, or pT4a (with bladder neck invasion), pNx (without pelvic lymph nodes dissection), or pN0 (with negative lymph nodes dissection) disease, and who had positive surgical margins were eligible for inclusion in the study. Eligible patients were randomly assigned (1:1) to either immediate adjuvant radiotherapy or delayed salvage radiotherapy at the time of biochemical relapse. Random assignment, by minimisation, was done using web-based software and stratified by Gleason score, pT stage, and centre. All patients received 6 months of triptorelin (intramuscular injection every 3 months). The primary endpoint was event-free survival. Efficacy and safety analyses were done on the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT00667069. FINDINGS: Between March 7, 2008, and June 23, 2016, 424 patients were enrolled. We planned to enrol 718 patients, with 359 in each study group. However, on May 20, 2016, the independent data monitoring committee recommended early termination of enrolment because of unexpectedly low event rates. At database lock on Dec 19, 2019, the overall median follow-up time from random assignment was 75 months (IQR 50-100), 74 months (47-100) in the adjuvant radiotherapy group and 78 months (52-101) in the salvage radiotherapy group. In the salvage radiotherapy group, 115 (54%) of 212 patients initiated study treatment after biochemical relapse. 205 (97%) of 212 patients started treatment in the adjuvant group. 5-year event-free survival was 92% (95% CI 86-95) in the adjuvant radiotherapy group and 90% (85-94) in the salvage radiotherapy group (HR 0·81, 95% CI 0·48-1·36; log-rank p=0·42). Acute grade 3 or worse toxic effects occurred in six (3%) of 212 patients in the adjuvant radiotherapy group and in four (2%) of 212 patients in the salvage radiotherapy group. Late grade 2 or worse genitourinary toxicities were reported in 125 (59%) of 212 patients in the adjuvant radiotherapy group and 46 (22%) of 212 patients in the salvage radiotherapy group. Late genitourinary adverse events of grade 2 or worse were reported in 58 (27%) of 212 patients in the adjuvant radiotherapy group versus 14 (7%) of 212 patients in the salvage radiotherapy group (p<0·0001). Late erectile dysfunction was grade 2 or worse in 60 (28%) of 212 in the adjuvant radiotherapy group and 17 (8%) of 212 in the salvage radiotherapy group (p<0·0001). INTERPRETATION: Although our analysis lacked statistical power, we found no benefit for event-free survival in patients assigned to adjuvant radiotherapy compared with patients assigned to salvage radiotherapy. Adjuvant radiotherapy increased the risk of genitourinary toxicity and erectile dysfunction. A policy of early salvage radiotherapy could spare men from overtreatment with radiotherapy and the associated adverse events. FUNDING: French Health Ministry and Ipsen.

Evaluation of genitourinary fistulas in pelvic malignancies with etiopathologic correlation: role of cross sectional imaging in detection and management.

OBJECTIVE: Genitourinary fistulas in pelvic malignancies are abnormal communications occurring due to either locally advanced tumours invading the surrounding organs or post-therapeutic complications of malignancies. In this article we review and describe the role of cross-sectional imaging findings in the management of genitourinary fistulas in pelvic malignancies. METHODS: A retrospective study, for the period January 2012 to December 2018, was undertaken in patients with pelvic malignancies having genitourinary fistulas. The cross-sectional (CT and MRI) imaging findings in various types of fistulas were reviewed and correlated with the primary malignancy and the underlying etiopathology. RESULTS: Genitourinary fistulas were observed in 71 patients (6 males, 65 females). 11 types of fistulas were identified in carcinomas of cervix, rectum, ovary, urinary bladder, sigmoid colon, vault, endometrium and prostate. The commonest were rectovaginal and vesicovaginal fistulas. 13 patients had multiple fistulas. The sensitivity, specificity, positive and negative predictive values of CT and MRI are 98%, 100%, 66%, 98% and 95%, 25%, 88% and 50% respectively. Contrast-enhanced CT with oral and rectal contrast is more sensitive and specific than MRI in the evaluation of genitourinary fistulas. CONCLUSION: Imaging findings significantly influence the management and outcome of genitourinary fistulas in pelvic malignancies. Contrast-enhanced CT is the imaging modality of choice in the evaluation of pelvic fistulas associated with malignancies and MRI is complimentary to it. ADVANCES IN KNOWLEDGE: To our knowledge, this study is the first of its kind wherein the mean duration of occurrence of fistulas in pelvic malignancies is correlated with the underlying etiopathology.

Temporal trend and survival impact of infection source among patients with sepsis: a nationwide study.

BACKGROUND: To determine the temporal trends of incidence and outcome based on different sources of sepsis using a nationwide administrative database. METHODS: From 2002 to 2012, the entire Taiwan's health insurance claims data of emergency-treated and hospital-treated sepsis were analysed for incidence and mortality trends. The information about patients with sepsis and sources of sepsis was identified using a set of validated International Classification of Diseases, ninth revision, clinical modification (ICD-9-CM) codes. The 30-day all-cause mortality was verified by linked death certificate database. RESULTS: A total of 1 259 578 episodes of sepsis were identified during the 11-year study period. Lower respiratory tract infection is the most common source of sepsis in patients, with the highest mortality rate. The incidence of genitourinary tract infection has the fastest growing rate. The sepsis mortality was declining at different rates for each source of sepsis. Co-infections in patients with sepsis are associated with higher mortality rate. CONCLUSION: The temporal trends of sepsis incidence and mortality varied among different sources of sepsis, with lower respiratory tract being the highest burden among patients with sepsis. Furthermore, sources of sepsis and the presence of co-infection are independent predictors of mortality. Our results support source-specific preventive and treatment strategies for future sepsis management.

[Current status of research on short-term quality of life after sphincteric-saving surgery in rectal cancer patients].

Sphincteric-saving surgery (SSS) is currently a hot spot in the treatment of mid-low rectal cancer. Although it preserves the anatomical continuity of the colon and anus, the postoperative functional outcomes and quality of life (QOL) remains to be confirmed. Current studies have shown that quality of life worsens at the first month after surgery, improves within 3-6 months, and stabilizes at about 1 year. The QOL was associated with patient-related factors, tumor-related factors, treatment-related factors and postoperative complications. For patient-related factors, younger patients have worse role function and sexual function but better cognitive function and physical function. Male patients deteriorate significantly in sexual and social function. For tumor-related factors, patients with lower rectal cancer have poorer defecation function. Those with advanced rectal cancer are more likely to suffer from side-effects related to chemotherapy. For treatment-related factors, patients undergoing intersphincteric resection have worse role function, body image and sexual interest. Preventive ileostomy results in the deterioration of role function, body image and sexual interest. Chemotherapy causes taste changes and chest pain. For postoperative complication, patients with anastomotic leakage have worse bowel function and psychological state. Patients with major low anterior resection syndrome and genitourinary dysfunction have worse global health score, social function and role function. In conclusion, short-term quality of life after sphincteric-saving surgery is acceptable. To improve QOL, specific intervention and guidance should be given to patients in this stage. Meanwhile, since many factors influence the quality of life simultaneously, researchers are confused about the questionnaire outcomes. Therefore, more specific and comprehensive tools are needed to evaluate QQL after sphincteric-saving surgery.

Association between Mental Disorders and Subsequent Medical Conditions.

BACKGROUND: Persons with mental disorders are at a higher risk than the general population for the subsequent development of certain medical conditions. METHODS: We used a population-based cohort from Danish national registries that included data on more than 5.9 million persons born in Denmark from 1900 through 2015 and followed them from 2000 through 2016, for a total of 83.9 million person-years. We assessed 10 broad types of mental disorders and 9 broad categories of medical conditions (which encompassed 31 specific conditions). We used Cox regression models to calculate overall hazard ratios and time-dependent hazard ratios for pairs of mental disorders and medical conditions, after adjustment for age, sex, calendar time, and previous mental disorders. Absolute risks were estimated with the use of competing-risks survival analyses. RESULTS: A total of 698,874 of 5,940,299 persons (11.8%) were identified as having a mental disorder. The median age of the total population was 32.1 years at entry into the cohort and 48.7 years at the time of the last follow-up. Persons with a mental disorder had a higher risk than those without such disorders with respect to 76 of 90 pairs of mental disorders and medical conditions. The median hazard ratio for an association between a mental disorder and a medical condition was 1.37. The lowest hazard ratio was 0.82 for organic mental disorders and the broad category of cancer (95% confidence interval [CI], 0.80 to 0.84), and the highest was 3.62 for eating disorders and urogenital conditions (95% CI, 3.11 to 4.22). Several specific pairs showed a reduced risk (e.g., schizophrenia and musculoskeletal conditions). Risks varied according to the time since the diagnosis of a mental disorder. The absolute risk of a medical condition within 15 years after a mental disorder was diagnosed varied from 0.6% for a urogenital condition among persons with a developmental disorder to 54.1% for a circulatory disorder among those with an organic mental disorder. CONCLUSIONS: Most mental disorders were associated with an increased risk of a subsequent medical condition; hazard ratios ranged from 0.82 to 3.62 and varied according to the time since the diagnosis of the mental disorder. (Funded by the Danish National Research Foundation and others; COMO-GMC ClinicalTrials.gov number, NCT03847753.).

DNA repair gene polymorphisms, tumor control, and treatment toxicity in prostate cancer patients treated with permanent implant prostate brachytherapy.

BACKGROUND: Radiotherapy and brachytherapy are common treatments for localized prostate cancer (PCa). However, very few studies evaluated the association of variations in DNA damage response genes and treatment outcomes and toxicity in brachytherapy-treated patients. PURPOSE: To evaluate the association of inherited germline variations in DNA repair-associated genes with tumor control and treatment toxicity in patients treated with low-dose-rate prostate brachytherapy (LDRB). MATERIAL AND METHODS: The cohort consists of 475 I-125 LDRB patients with a median follow-up of 51 months after seed implantation. Patients were genotyped for 215 haplotype tagging single nucleotide variations (htSNPs) in 29 candidate genes of DNA damage response and repair pathways. Their association with biochemical recurrence (BCR) was assessed using Cox regression models and Kaplan-Meier survival curves. Linear regressions and analysis of covariance (ANCOVA) between early and late International Prostate Symptom Score (IPSS) with htSNPs were used to evaluate the association with urinary toxicity. RESULTS: After adjustment for the established risk factors, six htSNPs in five genes were found to be significantly associated with an altered risk of BCR, with adjusted hazard ratios (HRadj. ) ranging between 3.6 and 11.1 (P < .05). Compared to carriers of the ERCC3 rs4150499C allele, patients homozygous for the T allele (n = 22) had a significant higher risk of BCR with a HR of 11.13 (IC95 = 3.9-32.0; P < .0001; q < 0.001). The Kaplan-Meier survival curve revealed a mean BCR-free survival time reduced from 213 ± 7 to 99 ± 12 months (log-rank P < .0001) for homozygous T carriers compare to noncarriers. For late IPSS (>6 months after treatment), htSNP rs6544990 from MSH2 showed a statistically significant b-coefficient of 1.85 ± 0.52 (P < .001; q < 0.1). Homozygous carriers of the MSH2 rs6544990C allele (n = 62) had a mean late IPSS 3.6 points higher than patients homozygous for the A allele (n = 132). This difference was significant when tested by ANCOVA using pretreatment IPSS as a covariate (P < .01). CONCLUSIONS: This study suggests an association of the intronic variants of the DNA nucleotide excision repair ERCC3 and DNA mismatch repair MSH2 genes with elevated risk of BCR and late urinary toxicity respectively after LDRB. Further validation is required before translational clinical advances.

Male partners of infertile couples with congenital unilateral absence of the vas deferens are mainly non-azoospermic.

BACKGROUND: Men with congenital unilateral absence of vas deferens were reported to be mainly azoospermic, with both unilateral renal absence and mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) but some have neither. OBJECTIVES: To assess whether in infertile couples the male partners with congenital unilateral absence of vas deferens are mainly azoospermic men. MATERIAL AND METHODS: Retrospective study in a unique university hospital; reproductive, clinical, CFTR analysis and seminal data of male partners of infertile couples (from 1998 to 2018) were analysed. Diagnosis of congenital unilateral absence of vas deferens was based on transrectal ultrasounds (TRUS): complete or partial absence of one vas deferens with complete contralateral vas deferens confirmed in 63 men. Distribution of sperm count in three classes: azoospermia, oligozoospermia or normozoospermia. Ultrasound determination of renal status; seminal biomarkers assays; and search for CFTR mutations. RESULTS: Among the 63 men, 39.7% displayed azoospermia, 27% oligozoospermia and 33.3% normozoospermia; 42% of the non-azoospermic men (16/38) had previously obtained a natural pregnancy. We found unilateral renal absence in 17/59 patients (29%). Among 50 men with CFTR testing, five carried an allele associated with cystic fibrosis belonging to the 29 men without renal anomalies, indicating a high allelic frequency (8.6%). The 63 patients displayed high rates of surgical histories for undescended testicles or inguinal hernia, low values of semen volume and of total seminal glycerophosphocholine. CONCLUSIONS: Our results indicate that men with congenital unilateral absence of vas deferens mainly display oligozoospermia or normozoospermia and that they were previously fertile. They clearly confirm, first, that CFTR testing is recommended in congenital unilateral absence of vas deferens men and it should be mandatory for those with normal kidneys; and, second, that TRUS is needed for the diagnosis of congenital unilateral absence of vas deferens. As congenital unilateral absence of vas deferens may be present whatever the sperm count, biological warnings are represented by semen volume and seminal epididymal markers and clinical warnings by surgical histories of undescended testes or inguinal hernia.

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes.

BACKGROUND: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS: Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS: Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment. CONCLUSIONS: Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

Salvage Stereotactic Body Radiation Therapy for Local Prostate Cancer Recurrence After Radiation Therapy: A Retrospective Multicenter Study of the GETUG.

PURPOSE: To assess the efficacy and safety of salvage stereotactic body radiation therapy (SBRT) in patients with biopsy-proven local prostate cancer recurrence after radiation therapy. METHODS AND MATERIALS: Between April 2010 and January 2017, 100 patients were included in 7 centers. Disease extension was assessed by pelvic multiparametric magnetic resonance imaging and choline positron emission tomography in 87% and 94% of patients, respectively. The median time interval between the 2 treatments was 7.5 years (range, 2-18). Median prostate-specific antigen at recurrence was 4.3 ng/mL (range, 2-38). Median SBRT dose was 36 Gy (range, 25-36.25) in 6 fractions (range, 5-6), every other day. Thirty-four percent of patients were treated by androgen deprivation therapy for a median duration of 12 months. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.03. RESULTS: Median follow-up was 29.3 months (range, 4-91). Second biochemical recurrence-free survival rate at 3 years was 55% (95% confidence interval [CI], 42%-66%). The initial D'Amico group, time interval after first radiation therapy, and SBRT dose were prognostic factors of biochemical recurrence-free survival in multivariate analysis (P = .09, P = .025, P = .018, respectively). No patient developed acute gastrointestinal toxicity of grade >1; rates of acute genitourinary toxicity of grade 2 and 3 were 8% and 1%, respectively. The actuarial 3-year grade ≥2 genitourinary and gastrointestinal toxicity was 20.8% (95% CI, 13%-29%) and 1% (95% CI, 0.1%-5.1%), respectively. One patient presented with neuritis of grade 3. CONCLUSIONS: With a short follow-up, this study shows that salvage SBRT allows for encouraging control and acceptable toxicity. Further prospective studies are necessary to confirm these preliminary results and to determine late toxicity.

Digestive and genitourinary sequelae in rectal cancer survivors and their impact on health-related quality of life: Outcome of a high-resolution population-based study.

BACKGROUND: With the rising number of rectal cancer survivors, more patients with sphincter-preserving surgery are having to live with a potentially impaired quality of life. The survey aimed to assess bowel and genitourinary sequelae and their impact on quality of life in an unselected registry-based population of rectal cancer survivors. METHODS: This cross-sectional cohort survey (registered at ClinicalTrials.gov; ID: NCT03459235) included patients with rectal cancer who underwent curative surgery with sphincter-preserving surgery from January 1, 2007 to January 31, 2015. Patients with recurrent disease, intestinal stoma, or cognitive disorders were excluded. Validated scoring system included the Urinary Symptom Profile in women and the International Prostate Symptom Score in men for urinary function, International Index for Erectile Function 5 in men and Female Sexual Function Index in women for sexual function, and Core 30/ Colo Rectal 29 questionnaires for quality of life and Low Anterior Resection Syndrome score for bowel function. The impact of functional sequelae on global quality of life was evaluated by multiple linear regression. RESULTS: Responders (45.3%, 92/203 patients) and nonresponders were comparable according to sex, age, tumor stage, and neoadjuvant chemoradiation. With a mean follow-up of 6.5 years, 65.2% of the rectal cancer survivors had bowel dysfunction, of whom 41.3% experienced major Low Anterior Resection Syndrome and 80% of rectal cancer survivors experienced genitourinary dysfunction. In multiple linear regression, poor bowel function was a significant predictor of global quality of life in men (P = .04) and women (P = .0003). CONCLUSION: This survey highlights the importance of sexual and bowel dysfunction in rectal cancer survivors and the strong correlation between high Low Anterior Resection Syndrome score and inferior quality of life. Further studies are needed to improve knowledge on how to predict bowel dysfunction and how to best support patients with bowel dysfunction.

Influence of transitioning of planning techniques in high-dose-rate brachytherapy monotherapy for clinically localized prostate cancer from two- to three-dimensional planning.

PURPOSE: The purpose of this study was to examine the influence of transitioning treatment planning techniques in high-dose-rate interstitial brachytherapy monotherapy for localized prostate cancer. METHODS AND MATERIALS: We compared 113 patients treated with initial two-dimensional treatment planning (2D: 74% received 54 Gy/nine fractions) to 240 patients treated with three-dimensional planning (3D: 70 CT image-guided 3D [CT-3D]: 84% 45.5 Gy/seven fractions and 170 MRI image-guided [MRI-3D]: 87% received 49 Gy/nine fractions). RESULTS: The actuarial 5-year biochemical failure-free survival rates for 2D and 3D planning were 88.4% and 95.1% (p = 0.0285 between 2D and 3D) (89.4% in CT-3D and 97.5% in MRI-3D), respectively; the rates for 2D and 3D planning were not available and 100% in the low-risk group (100% and 100%), 97.7% and 94.5% (p = 0.7626) (85.1% and 100%) in the intermediate-risk group, and 82.5% and 94.4% (p = 0.0507) (93.8% and 94.7%) for the high-risk group. Late gastrointestinal (GI) toxicity Grade 1, Grade 2, and Grade 3 was found in 13%, 4%, and 1% in 2D, whereas 8%, 2%, and 0% in 3D group (p = 0.0699), respectively. 3D decreased GI toxicity Grade 2 ≤ than 2D (19% and 10%, p = 0.0169). Late genitourinary toxicity Grade 1, Grade 2, and Grade 3 was 21%, 12%, and 3% for 2D and 32%, 18%, and 3% for 3D, respectively (p = 0.0217). CONCLUSIONS: The 3D technique has the potential to reduce GI toxicity and improve biochemical control rate compared to 2D planning, whereas 3D resulted in increased mild genitourinary toxicity.

Genitourinary Complications Are a Leading and Expensive Cause of Emergency Department and Inpatient Encounters for Persons With Spinal Cord Injury.

OBJECTIVES: To determine the rates of emergency department (ED) visits and inpatient hospitalizations for genitourinary (GU) complications after spinal cord injury (SCI) using a national sample; to examine which patient and facility factors are associated with inhospital mortality; and to estimate direct medical costs of GU complications after SCI. DESIGN: Retrospective cross-sectional and cost analysis of the 2006 to 2015 National Inpatient Sample and National Emergency Department Sample from the Healthcare Cost and Utilization Project. PARTICIPANTS: SCI-related encounters using various International Classification of Disease, Ninth Edition, Clinical Modification diagnosis codes. The inpatient sample included 1,796,624 hospitalizations, and the ED sample included 618,118 treat-and-release visits. MAIN OUTCOME MEASURES: The exposure included a GU complication, identified by International Classification of Disease, Ninth Edition, Clinical Modification codes 590-599. The outcomes then included an ED visit or hospitalization, death prior to discharge, and direct medical costs estimated from reported hospital charges. RESULTS: For the inpatient sample, we observed a 2.5% annual increase (95% confidence interval [CI], 1.8-3.2) in the proportion of SCI-related hospitalizations with any GU complication from 2006 to 2011, and a lesser rate of increase of 0.9% (95% CI, 0.4-1.4) each year from 2011 to 2015. Age, level of injury, and payer source were correlated to inhospital mortality. The costs of GU-related health care use exceeded $4 billion over the study period. CONCLUSIONS: This study shows the rates and economic burden of health care use associated with GU complications in persons with SCI in the United States. The need to develop strategies to effectively deliver health care to the SCI population for these conditions remains great.