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.

Transurethral collagen injections for male intrinsic sphincter deficiency: the University of Texas-Houston experience.

PURPOSE: Injectable agents are used to increase urethral coaptation for the treatment of intrinsic sphincter deficiency. We evaluated the long-term results and complications of transurethral collagen injections in males. MATERIALS AND METHODS: We reviewed the charts of 322 men (mean age 67.2 years, range 40 to 91) with intrinsic sphincter deficiency after therapy for prostate carcinoma (307) or benign prostatic hyperplasia (15) who received transurethral collagen injections. The analysis included types and combinations of treatment for prostate cancer or benign prostatic hyperplasia, pre-procedure voiding symptoms, total collagen received, maximal percentage improvement and durability of effect. RESULTS: The mean length of followup was 40.1 (+/-13.2) months. Overall, the mean number of injections was 4.37 (+/-2.09). Mean percent improvement after a series of injections was 44.59 (+/-38.26). Mean pad use before and after injection was statistically different (5.15 vs 2.98, p=0.0001). Mean duration of response was 6.3 (+/-8.14) months. In those who achieved complete continence (17%), the mean duration of response was 11.1 (+/-8.87) months. Within this group the mean number of injections and ml of collagen injected were 3.83 and 29.27, respectively. Five patients (1.5%) complained of a quantitative increase in leakage after their series of collagen injections. CONCLUSIONS: Transurethral collagen injections are a good option for short-term therapy in men with post-prostatectomy incontinence. The mean number of injections to achieve a plateau is 3 to 4, regardless of initial severity of incontinence. Those in the radical prostatectomy only treatment group are statistically more likely to achieve continence than all other treatment groups.

Contemporary morbidity from lymphadenectomy for penile squamous cell carcinoma: the M.D. Anderson Cancer Center Experience.

PURPOSE: Inguinal lymphadenectomy can be curative in patients with small volume inguinal metastases and those with more significant adenopathy responding to combination chemotherapy. However, several series collected for 15 to 40 years attest to the significant morbidity associated with lymphadenectomy. We reviewed our recent experience with lymphadenectomy in patients with invasive penile cancer who were judged to require inguinal staging and therapeutic procedures to assess the incidence and magnitude of complications caused by this procedure, especially in those with no palpable adenopathy (prophylactic group). MATERIALS AND METHODS: A total of 106 lymphadenectomy procedures were performed in 53 patients. The indications for dissection were prophylactic in 66 (62%) patients in whom a superficial dissection alone was completed on the ipsilateral side, therapeutic in 28 (26%) in whom superficial, deep and ipsilateral pelvic dissections were performed, and palliative in 12 (11%) undergoing extensive resection of inguinal and abdominal wall tissue after chemotherapy. Minor postoperative complications included those requiring local wound débridement in the clinic, mild to moderate leg edema, seroma formation not requiring aspiration and minimal skin edge necrosis requiring no therapy. Major complications included severe leg edema interfering with ambulation, skin flap necrosis requiring a skin graft, rehospitalization, deep venous thrombosis, death, or reexploration or other invasive procedures performed in the operating room. The incidence and magnitude of complications were compared with prior reports from our center and other series. RESULTS: A total of 41 (68%) minor and 19 (32%) major complications occurred with the 106 dissections (31 of 53 patients, 58%). Prophylactic and therapeutic dissections were associated with a lower incidence of complications compared with palliative dissections (p = 0.017 to 0.049). The incidence of major complications also trended lower in the prophylactic group compared with other indications (p = 0.05). One patient in the palliative group died of sepsis on postoperative day 15. When compared with 3 prior series, the incidence of skin edge necrosis in our series was significantly lower (8% versus 45% to 62%, p <0.0001). Similarly, the incidence and severity of edema in our series were significantly lower than in a prior report from our institution (23% versus 50%, p <0.0001). CONCLUSIONS: For select patients undergoing prophylactic inguinal dissection to detect the presence of microscopic metastases, the incidence and magnitude of complications appeared acceptable in our contemporary experience. Similarly the morbidity of therapeutic lymphadenectomy appeared acceptable, considering the potential therapeutic benefit. However, significant complications, including death, can be associated with palliative groin dissection. Optimal candidates are those having a significant response to systemic chemotherapy whose groins are grossly uninfected.