Efficacy of National Comprehensive Cancer Network Guidelines in Identifying Pathogenic Germline Variants Among Unselected Patients with Prostate Cancer: The PROCLAIM Trial.

BACKGROUND: Prostate cancer (PCa) patients with pathogenic/likely pathogenic germline variants (PGVs) in cancer predisposition genes may be eligible for U.S. Food and Drug Administration-approved targeted therapies, clinical trials, or enhanced screening. Studies suggest that eligible patients are missing genetics-informed care due to restrictive testing criteria. OBJECTIVE: To establish the prevalence of actionable PGVs among prospectively accrued, unselected PCa patients, stratified by their guideline eligibility. DESIGN, SETTING, AND PARTICIPANTS: Consecutive, unselected PCa patients were enrolled at 15 sites in the USA from October 2019 to August 2021, and had multigene cancer panel testing. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Correlates between the prevalence of PGVs and clinician-reported demographic and clinical characteristics were examined. RESULTS AND LIMITATIONS: Among 958 patients (median [quartiles] age at diagnosis 65 [60, 71] yr), 627 (65%) had low- or intermediate-risk disease (grade group 1, 2, or 3). A total of 77 PGVs in 17 genes were identified in 74 patients (7.7%, 95% confidence interval [CI] 6.2-9.6%). No significant difference was found in the prevalence of PGVs among patients who met the 2019 National Comprehensive Cancer Network Prostate criteria (8.8%, 43/486, 95% CI 6.6-12%) versus those who did not (6.6%, 31/472, 95% CI 4.6-9.2%; odds ratio 1.38, 95% CI 0.85-2.23), indicating that these criteria would miss 42% of patients (31/74, 95% CI 31-53%) with PGVs. The criteria were less effective at predicting PGVs in patients from under-represented populations. Most PGVs (81%, 60/74) were potentially clinically actionable. Limitations include the inability to stratify analyses based on individual ethnicity due to low numbers of non-White patients with PGVs. CONCLUSIONS: Our results indicate that almost half of PCa patients with PGVs are missed by current testing guidelines. Comprehensive germline genetic testing should be offered to all patients with PCa. PATIENT SUMMARY: One in 13 patients with prostate cancer carries an inherited variant that may be actionable for the patient's current care or prevention of future cancer, and could benefit from expanded testing criteria.

A prospective, multicenter, international study to explore the effect of three different amplitude settings in female subjects with urinary urge incontinence receiving interstim therapy.

AIMS: The aim of this study is to evaluate the effect of sub-sensory amplitude settings of sacral neuromodulation therapy on overactive bladder symptoms in subjects with urinary urge incontinence. METHODS: Subjects who qualified for a neurostimulator device implant were randomized to one of three amplitude settings (50% of sensory threshold [ST], 80% of ST, and ST). Subjects completed urinary voiding diaries (3-day), International consultation on incontinence modular questionnaire-overactive bladder symptoms quality of life questionnaire, and patient global impression of improvement (PGI-I) to assess change in voiding symptoms and quality of life (QoL) from baseline through 12 weeks. RESULTS: Forty-eight subjects had a successful test stimulation, 46 were implanted with a neurostimulator device and 43 completed the 12-week follow-up visit. The change from baseline to 12 weeks is -3.0 urinary incontinence (UI) episodes/day (95% confidence interval [CI]: -4.4 to -1.7) for the 50% of sensory threshold group, -2.9 UI episodes/day (95% CI: -4.7 to -1.2) for 80% of sensory threshold group, and -3.6 UI episodes/day (95% CI: -5.2 to -1.9) for the sensory threshold group. In each randomized group, improvements were observed in health-related QoL, its subscales, and symptom interference. Subjects across all three randomization groups reported on the PGI-I that their bladder condition was better at 12 weeks compared to before they were treated with InterStim therapy. CONCLUSION: These findings provide insights into possible advancements in the postimplantation phase of therapy with potential for improved patient comfort and increased device longevity.

Outcomes in Renal Cell Carcinoma With IVC Thrombectomy: A Multiteam Analysis Between an NCI-Designated Cancer Center and a Quaternary Care Teaching Hospital.

INTRODUCTION: Interteam performance and Clavien-Dindo (C-D) complications in renal cell carcinoma with inferior vena cava thrombectomy (RCC-IVCT) have not been reported. We aimed to describe complications by the degree of complexity and surgical teams in a collaborative effort between a National Cancer Institute-designated Comprehensive Cancer Center and a Quaternary Care Teaching Hospital. METHODS: Between January 2011 and May 2019, 73 consecutive RCC-IVCT were included. C-D grades III or higher were captured. Teams involved were urologic-oncology, vascular, hepatobiliary/transplant, and cardiothoracic. The Mayo Clinic tumor thrombus classification was used. RESULTS: Overall complication rate was 42% (n = 31). Nineteen percent had grade III, 18% had grade IV, and 6% had grade V complications. Patients with level IV thrombus had the highest in-hospital mortality rate (75%). Thrombus level did not show a correlation to complication rates (14% level I, 45% level II, 32% level III, 42% level IV). A positive correlation found between the number of teams involved and complication rates (35% with 2-team, 59% with 3-team, P = .059). Thromboembolic events (6% vs 24%, P = .02) and disposition other than home (22% vs 48%, P = .01) were statistically lower for the 2-team groups. Two-team in-hospital mortality was 1/51 (2%) versus 3-team (3/22,14%, (P = .07). No statistical differences were found in infections, thromboembolic events, and grades of complications between surgical teams. CONCLUSIONS: Despite similar interteam performance, the consistency of surgeons in high complexity cases could improve outcomes further. Complexity was higher for hepatobiliary/transplant and cardiothoracic teams. A combination of intraoperative events and patient selection (comorbidities and age) contributed to death. Overall, in-hospital mortality was lower than in most reported series.

Transvaginal paravaginal repair of high-grade cystocele central and lateral defects with concomitant suburethral sling: report of early results, outcomes, and patient satisfaction with a new technique.

Baden-Walker classification grade III-IV (pelvic organ prolapse quantification [POP-Q] system stage III-IV) cystocele is associated with a constellation of abnormalities including urethral hypermobility, lateral defect, central defect, and concomitant vault and posterior wall prolapse. We describe a new transvaginal paravaginal technique to correct this group of abnormalities and report on our early results. We prospectively evaluated patients with high-grade cystocele who underwent repair with the new transvaginal paravaginal repair. Preoperative evaluation included history and physical examination, dynamic pelvic magnetic resonance imaging, urodynamics, and symptom questionnaire. All patients first underwent a distal urethral polypropylene sling surgery. After repair of the central defect of the cystocele, a paravaginal repair of the lateral defect was performed by using a circular 5 cm x 5 cm soft polypropylene mesh attached proximally to the sacrouterine/cardinal ligament, distally to the bladder neck, and laterally to the infralevator obturator fascia. Postoperative evaluation at 3-month intervals included history and physical examination using the POP-Q system, a voiding dysfunction and incontinence symptom questionnaire, the validated short form of the Urogenital Distress Inventory (UDI-6), a validated global quality-of-life question, and a postvoid residual. We performed the repair in 98 patients with a mean age of 65 years (range, 40 to 86 years). Of these, 26% underwent concomitant vaginal hysterectomy, 45% had enterocele repair, and 94% had rectocele repair. There were 2 complications, including transient ureteral obstruction due to bladder wall hematoma and 1 patient who presented with a recurrent enterocele requiring surgical repair. No patient experienced urinary retention. De novo stress urinary incontinence was seen in 3 patients; de novo urge incontinence was seen in 2 patients. Postoperative POP-Q scores showed 85% of patients with stage 0-I, 13% with stage II, and 2% with stage III anterior vaginal wall prolapse. Of patients with preoperative stress urinary incontinence, 70% reported never experiencing symptoms under any circumstances. Quality of life improved from 4.7 to 1 (P < 0.005). Transvaginal paravaginal repair of grade III-IV cystocele using soft polypropylene mesh fixed to the obturator fascia, sacrouterine ligaments, and bladder neck area provides excellent support of the central defect repair as well as repair of the lateral defect. The operation is safe, simple, and outpatient based, and provides excellent anatomic results with minimal complications. Concomitant distal polypropylene sling did not increase the rate of complications and did not compromise results of stress urinary incontinence surgery.

Anterior vaginal wall surgery in elderly patients: outcomes and assessment.

OBJECTIVES: To evaluate the efficacy, safety, and impact on quality of life of anterior vaginal surgery in the elderly. Incontinence in the elderly is a devastating medical and social condition accounting for 50% of admissions to nursing homes; the incidence of anterior vaginal wall prolapse also increases in the elderly. Most patients are treated conservatively, because of a reluctance to offer surgical treatment to this age group owing to the perceived increased risk of complications and decreased rate of treatment success. METHODS: We prospectively evaluated all consecutive elderly patients who underwent anterior vaginal wall surgery between November 1999 and May 2003. The surgical outcomes were determined by the symptom, bother, and quality-of-life questionnaires answered by the patients. The physicians were unaware of the patients' responses. RESULTS: A total of 209 patients were available for analysis. The mean age was 70 years (range 65 to 88) and the mean follow-up 15.3 months. All items in the symptom and bother questionnaires showed significant improvement. Significant improvement was also demonstrated in quality of life and pad use (P <0.005). No significant perioperative complications occurred. Only patients older than 71 years of age did not experience an improvement in the symptom scores for urge incontinence. Nevertheless, as for all other patients, older patients experienced improvement in stress urinary incontinence (SUI) symptoms, the bother scores of SUI and urge incontinence, and quality of life. CONCLUSIONS: Surgical treatment of anterior vaginal wall prolapse and SUI in the elderly is effective and safe and significantly improves the quality of life of these patients.

Impact of vaginal surgery for stress urinary incontinence on female sexual function: is the use of polypropylene mesh detrimental?

OBJECTIVES: To evaluate prospectively the impact of a distal urethral polypropylene sling on sexual function using a validated questionnaire. Suburethral slings are currently the most common anti-incontinence surgery performed. Although the use of polypropylene is safe and effective, concern exists that the presence of the material in the vagina may adversely affect sexual function. METHODS: A total of 29 patients agreed to participate in this prospective study. The patients were evaluated with the Female Sexual Function Index, a validated, 19-item questionnaire that assesses six domains of sexual function: desire, arousal, lubrication, orgasm, satisfaction, and pain. The questionnaires were administered at 6-month intervals during the follow-up visits. RESULTS: The mean patient age was 52 years (range 38 to 72). The mean duration of follow-up was 19.4 months (range 7 to 37). No statistically significant difference was found in sexual function after placement of a distal urethral polypropylene sling. Of the 29 patients, 14% were not sexually active before or after surgery. No statistically significant difference was found between preoperative and postoperative desire, arousal, lubrication, orgasm, satisfaction, and pain. CONCLUSIONS: No change was found in overall sexual function in women undergoing placement of a mid to distal polypropylene urethral sling. Specifically, neither a deleterious effect nor statistically significant improvement was found in sexual desire, arousal, lubrication, orgasm, satisfaction, or pain compared with the preoperative baseline values.

Synthetic sling options for stress urinary incontinence.

In the past decade, sling surgery has become the preferred technique for the management of female stress urinary incontinence. A greater understanding of the pathogenesis of stress urinary incontinence and a greater durability and effectiveness for sling surgery has allowed this technique to become the benchmark for treatment of female stress urinary incontinence. As a consequence, a multitude of products have been developed using various techniques and materials to perform sling surgery. This article reviews the materials and techniques available and the complications associated with each. Most importantly, the outcomes are discussed so that the readers can best understand the impact of these surgeries on our patients.

1-step removal of encrusted retained ureteral stents.

PURPOSE: Ureteral stents are prone to encrustation, which can create a problem at the time of removal. Reports in the literature describe techniques that require several procedures and anesthetic sessions to effect extraction. We describe our experience with 1-step removal of retained ureteral stents. MATERIALS AND METHODS: A total of 12 retained calcified ureteral stents in 10 patients were treated between December 1998 and July 2002. The reason for stent placement was nephrolithiasis in 8 patients, ureteral obstruction due to malignancy in 1 and following endopyelotomy in 1. Stents were in place for a mean of 10 months (range 6 to 16). One patient had 2 retained stents in a single ureter. Stents were extracted using a holmium laser. The semirigid ureteroscope and/or flexible ureteroscope was advanced beside the retained ureteral stent and laser was used to fragment stone on and around the stent. The ureteroscope was advanced into the renal pelvis and any stone present was fragmented. The ureteroscope and stent were then removed. RESULTS: Of the 12 stents 11 were managed by ureteroscopy alone. In 1 patient the upper stone burden was treated through a percutaneous tube previously placed for obstructive pyelonephritis. All patients were treated at 1 anesthetic session. Mean operative time was 93 minutes (range 45 to 225). All except 2 patients were discharged home in 23 hours. In 1 patient a perinephric abscess resolved with computerized tomography guided drainage. One patient required intravenous antibiotics for 48 hours for fever with subsequent resolution. No patients have had ureteral strictures to date. CONCLUSIONS: Historically the management of retained calcified ureteral stents has involved several operations to render the patient stone-free and stent-free. We describe our approach to this difficult problem with only 1 session in the operating room, minimal morbidity and a short hospital stay.

Continent colonic urinary reservoir (Florida pouch): long-term surgical complications (greater than 11 years).

PURPOSE: We analyzed the long-term results (greater than 10 years) of a continent cutaneous colonic urinary reservoir (Florida pouch), focusing primarily on the incidence of significant complications. MATERIALS AND METHODS: Between January 1986 and October 1991, 179 patients underwent continent cutaneous colonic urinary reservoir construction. Of these patients 105 died of primary disease or were lost to followup, leaving 38 males and 36 females with a mean followup of 133 months with adequate data for analysis who are the subject of this report. The surgical technique has been previously reported. Briefly, a detubularized right colonic segment forms the reservoir, a tapered external limb reinforced at the ileocecal valve level allows continent catheterization and the ureters are directly anastomosed to the pouch. The diseases that prompted urinary diversion included bladder cancer in 28 cases, conversion from another diversion in 12, neurogenic bladder in 11, interstitial cystitis in 10, crippling incontinence in 4, radiation cystitis in 6, hemorrhagic cystitis in 1, exstrophy in 1 and colon cancer in 1. A total of 146 direct ureterocolonic reimplantations were performed. RESULTS: Complications were grouped by etiology and the number of patients, including abdominal wall (peristomal hernia in 3 patients or 4%), external limb (incontinence in 5 or 6.7%, stomal stenosis in 3 or 4% and difficult catheterization in 1 or 1.4%), reservoir stones (4 or 5.4%), ureteral obstruction (primary reimplantation in 7 of 108 or 6.3%, repeat reimplantation in 4 of 24 or 16.4% and radiated ureters in 4 of 14 or 28.4%) and metabolic (persistent diarrhea in 2 or 2.7%, renal failure in 2 or 2.7% and low vitamin B12 in 3 or 4%). Severe acidosis developed in 4 individuals (5.5%). Of the 12 patients who underwent conversion from another type of diversion 7 (58%) experienced metabolic alterations. CONCLUSIONS: In the long term continent colonic reservoirs have an acceptable complication rate. The most common problem is ureteral obstruction, especially in patients who have previously undergone irradiation (28.4% versus 6.3%, Fisher's test p = 0.02). Patients in whom longer bowel segments were resected, such as those with conversion from another type of diversions, experienced a greater number of complications, especially ureteral obstruction associated with repeat reimplantation (16.4% versus 6.3%, Fisher's test p = 0.23) and metabolic derangements (58% versus 6.4%, Fisher's test p = 0.0001).