Urology
Meta-Analysis: Long Half-Life Phosphodiesterase Inhibitors Reduce HbA1c in Adults with Elevated Baseline Levels
6 Jan, 2025 | 08:00h | UTCBackground: Phosphodiesterase type 5 (PDE5) inhibitors are traditionally used to treat erectile dysfunction and pulmonary arterial hypertension. Recent evidence suggests that PDE5 inhibitors could also be repurposed to lower hemoglobin A1c (HbA1c) in patients with type 2 diabetes. Given the disparity in half-lives among these agents, this meta-analysis focused on whether longer half-life PDE5 inhibitors (tadalafil, PF-00489791) produce a more sustained HbA1c reduction compared to short half-life PDE5 inhibitors (sildenafil, avanafil).
Objective: To evaluate the effect of PDE5 inhibitors on HbA1c levels in individuals with baseline values above 6%, comparing agents with short and long half-lives to assess differential clinical benefits in glycemic control.
Methods: This systematic review and meta-analysis included only randomized controlled trials (RCTs) in which participants received any PDE5 inhibitor for at least four weeks, with control or placebo for comparison. Major databases (Cochrane CENTRAL, PubMed Central, ClinicalTrials.gov, and WHO ICTRP) were searched through September 2024 without language restrictions. Statistical analyses were performed using a random-effects model, reporting mean differences in HbA1c. Secondary outcomes (HOMA-IR, lipid profiles, fasting glucose, and others) were also explored.
Results: Thirteen RCTs were eligible (N=1083). Long half-life agents showed a significant mean reduction of approximately −0.40% in HbA1c (p=0.002) in the overall analysis, whereas short half-life PDE5 inhibitors exhibited no significant change. In more stringent subgroup analyses (≥8 weeks’ duration, exclusive type 2 diabetes, baseline HbA1c ≥6.5%), long half-life PDE5 inhibitors maintained a significant decrease (−0.50%), while short half-life agents paradoxically showed a slight but significant increase (+0.36%, p=0.03). In trials enrolling patients with poorly controlled diabetes (baseline HbA1c near 10%), tadalafil’s HbA1c reductions were considerably larger, aligning with the efficacy of other standard oral antidiabetic medications.
Conclusions: Long half-life PDE5 inhibitors appear to confer meaningful reductions in HbA1c, comparable to established oral antidiabetic agents, particularly in patients whose HbA1c is inadequately controlled. In contrast, short half-life PDE5 inhibitors did not show a consistent benefit and may paradoxically raise HbA1c in certain subgroups, although further large-scale studies are warranted to confirm these findings.
Implications for Practice: Long half-life PDE5 inhibitors could serve as an adjunctive therapy in type 2 diabetes management, especially in individuals with higher baseline HbA1c. Yet, caution is advised given limited data on adverse events and the short duration of most included trials. Physicians should remain prudent until more robust evidence, especially in populations with markedly elevated HbA1c, becomes available.
Study Strengths and Limitations: Strengths include a direct comparison between short and long half-life PDE5 inhibitors in a clinically relevant population, plus systematic subgroup analyses. Limitations involve heterogeneity in trial designs, relatively low baseline HbA1c in most participants, and a lack of long-term follow-up data or major clinical endpoints.
Future Research: Subsequent trials should target populations with poorly controlled diabetes (HbA1c ≥9.0%) and assess longer durations (≥3 months) to capture the full impact of PDE5 inhibitor therapy. A deeper examination of combination regimens, pharmacokinetic optimization, and clinical outcomes like cardiovascular events would further clarify the role of these agents in diabetes care.
Reference: Kim J, Zhao R, Kleinberg LR, Kim K. (2025) “Effect of long and short half-life PDE5 inhibitors on HbA1c levels: a systematic review and meta-analysis.” eClinicalMedicine, 80, 103035. Available at: DOI: http://doi.org/10.1016/j.eclinm.2024.103035
Guideline: Doxycycline Postexposure Prophylaxis to Reduce Bacterial STI Incidence in High-Risk Populations
19 Dec, 2024 | 22:32h | UTCIntroduction: This summary presents key recommendations from the 2024 Centers for Disease Control and Prevention (CDC) guidelines on using doxycycline postexposure prophylaxis (doxyPEP) to prevent bacterial sexually transmitted infections (STIs), including syphilis, gonorrhea, and chlamydia. Targeting men who have sex with men (MSM) and transgender women with at least one bacterial STI in the past 12 months, these guidelines aim to reduce recurrence rates and improve sexual health outcomes through timely prophylactic intervention.
Key Recommendations:
- Offer doxyPEP counseling to MSM and transgender women with a recent bacterial STI history, addressing the benefits, harms, and uncertainties of prophylactic doxycycline use.
- Advise eligible patients to take a single 200 mg dose of doxycycline as soon as possible (ideally within 72 hours) following condomless oral, anal, or vaginal sexual exposure to reduce their subsequent STI risk.
- Reinforce periodic screening (every 3–6 months) for STI markers, including syphilis and HIV serologies, as well as nucleic acid amplification tests for gonorrhea and chlamydia at relevant anatomical sites.
- Integrate doxyPEP into comprehensive sexual health services that include risk-reduction counseling, condom use, recommended immunizations, and linkage to HIV preexposure prophylaxis (PrEP) or HIV care, thereby enhancing overall prevention strategies.
- Consider extending doxyPEP to other high-risk groups, including heterosexual individuals with recurrent STIs, guided by clinical judgment and shared decision-making.
- Monitor and address adverse events, particularly gastrointestinal symptoms, and acknowledge the potential for antimicrobial resistance. Continued vigilance is warranted given the risk of resistance in commensal flora and key STI pathogens, such as Neisseria gonorrhoeae.
- Assess social and ethical dimensions of doxyPEP implementation, ensuring equitable access and minimizing potential harms, including stigma or intimate partner violence related to prophylaxis disclosure.
Conclusion: Implementing doxyPEP for MSM and transgender women who have experienced a recent bacterial STI can substantially lower the incidence of recurrent infections. By combining prophylactic doxycycline with routine surveillance, comprehensive preventive services, and careful consideration of resistance patterns, clinicians may enhance patient care and strengthen STI control efforts. Further investigation is needed to establish efficacy in cisgender women, transgender men, nonbinary persons, and other populations at risk. Longer-term, population-based studies focused on antimicrobial resistance and community-level effects will help guide sustainable and equitable use of this prevention strategy.
Cohort Study: High Rate of Preventable Adverse Events in Surgical Inpatients
16 Nov, 2024 | 17:29h | UTCBackground: Adverse events during hospital admissions, particularly in surgical settings, remain a significant cause of patient harm despite efforts to improve patient safety since the “To Err is Human” report. Advances in surgical techniques and patient care necessitate an updated assessment of the current state of perioperative safety.
Objective: To estimate the frequency, severity, and preventability of adverse events associated with perioperative care in surgical inpatients and to identify the settings and healthcare professionals involved.
Methods: A multicenter retrospective cohort study was conducted across 11 US hospitals in Massachusetts. A weighted random sample of 1,009 patients was selected from 64,121 adults admitted for surgery in 2018. Trained nurses reviewed electronic health records to identify adverse events, which were then adjudicated by physicians. Adverse events were classified by type, severity, preventability, setting, and professions involved.
Results: Adverse events occurred in 38.0% of patients (95% CI, 32.6–43.4%), with major adverse events in 15.9% (12.7–19.0%). Among 593 adverse events identified, 59.5% were potentially preventable, and 20.7% were definitely or probably preventable. The most common events were surgery-related (49.3%), adverse drug events (26.6%), healthcare-associated infections (12.4%), and patient care events (11.2%). Adverse events most frequently occurred in general care units (48.8%) and involved attending physicians (89.5%) and nurses (58.9%).
Conclusions: More than one-third of surgical inpatients experienced adverse events, with nearly half classified as major and most potentially preventable. These findings highlight the critical need for ongoing improvement in patient safety throughout perioperative care involving all healthcare professionals.
Implications for Practice: Healthcare providers should enhance patient safety protocols across all perioperative settings, not just in operating rooms. Emphasis should be placed on preventing surgery-related complications, adverse drug events, and healthcare-associated infections by fostering teamwork and continuous monitoring.
Study Strengths and Limitations: Strengths include a comprehensive review of medical records and systematic classification of adverse events by trained professionals. Limitations involve the study’s confinement to Massachusetts hospitals in 2018, potential variability in documentation practices, and limited sample size affecting generalizability and specialty-specific estimates.
Future Research: Further studies are needed to assess adverse event rates in diverse geographic locations and healthcare systems, explore effective interventions to reduce preventable harm, and evaluate long-term trends in surgical patient safety.
Guideline: Management of Urinary Tract Infections in Pediatrics and Adults
5 Nov, 2024 | 18:59h | UTCIntroduction: Urinary tract infections (UTIs) are among the most common infections worldwide, significantly impacting patient quality of life and imposing substantial clinical and economic burdens. Despite advancements in diagnosis and treatment, UTIs continue to cause high morbidity and mortality, ranging from simple cystitis to life-threatening sepsis. Addressing the discrepancy between evidence quality and recommendation strength in existing guidelines, the WikiGuidelines Group has developed a consensus statement. This guideline aims to provide evidence-based recommendations for the prevention, diagnosis, and management of UTIs across diverse clinical settings.
Key Recommendations:
- Cranberry Products:
- Recommendation: Cranberry juice or supplements are recommended for preventing symptomatic, culture-verified UTIs in women with recurrent UTIs, children, and individuals susceptible after interventions.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Methenamine Hippurate:
- Recommendation: Methenamine hippurate is recommended as an alternative to prophylactic antibiotics for preventing recurrent UTIs in patients with intact bladder anatomy.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Topical Estrogen:
- Recommendation: Vaginal estrogen therapy is recommended for postmenopausal women to reduce recurrent UTIs by restoring the vaginal microbiome.
- Quality of Evidence: High
- Recommendation Strength: Strong
- Empirical Treatment Regimens:
- Recommendation: For uncomplicated cystitis, nitrofurantoin is recommended as a first-line agent. For pyelonephritis, trimethoprim/sulfamethoxazole or a first-generation cephalosporin are reasonable first-line agents, depending on local resistance rates.
- Quality of Evidence: Moderate
- Recommendation Strength: Strong
- Treatment Duration for Acute Cystitis in Adults:
- Recommendation:
- Nitrofurantoin: 5 days
- Trimethoprim/sulfamethoxazole: 3 days
- Oral fosfomycin: Single dose
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Treatment Duration for Acute Pyelonephritis in Adults:
- Recommendation:
- Fluoroquinolones: 5–7 days
- Dose-optimized β-lactams: 7 days
- Quality of Evidence: High
- Recommendation Strength: Strong
- Recommendation:
- Antimicrobial Stewardship:
- Recommendation: De-escalation of antibiotics and the use of mostly or all oral treatment regimens are recommended to optimize antimicrobial use and reduce adverse effects.
- Quality of Evidence: High
- Recommendation Strength: Strong
Conclusion: The consensus highlights a significant lack of high-quality prospective data in many areas related to UTIs, limiting the ability to provide clear recommendations. Implementing these evidence-based guidelines can enhance patient care by promoting effective prevention strategies, accurate diagnosis based on clinical symptoms, appropriate treatment durations, and robust antimicrobial stewardship. This approach is expected to improve clinical outcomes, reduce antimicrobial resistance, and preserve the effectiveness of current treatments.
Observational Study: Kidney Transplantation from Donors with HIV Safe for Recipients with HIV
20 Oct, 2024 | 17:30h | UTCBackground: Kidney transplantation improves survival for persons with HIV and end-stage renal disease but is limited by organ shortages. Transplantation from donors with HIV to recipients with HIV is emerging under the HIV Organ Policy Equity (HOPE) Act but is currently approved only for research. The Department of Health and Human Services is considering expanding this practice to clinical care, but data are limited to small case series without control groups.
Objective: To assess whether kidney transplantation from donors with HIV is noninferior to transplantation from donors without HIV regarding safety outcomes in recipients with HIV.
Methods: In an observational, noninferiority study at 26 U.S. centers, 408 transplantation candidates with HIV were enrolled. Of these, 198 received a kidney transplant: 99 from deceased donors with HIV and 99 from deceased donors without HIV. The primary outcome was a composite safety event (death, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (upper bound of 95% CI for hazard ratio ≤3.00). Secondary outcomes included overall survival, survival without graft loss, rejection rates, infections, cancer, and HIV superinfection.
Results: The adjusted hazard ratio for the composite primary outcome was 1.00 (95% CI, 0.73 to 1.38), demonstrating noninferiority. Overall survival at 1 year was 94% for recipients of kidneys from donors with HIV and 95% for those from donors without HIV; at 3 years, survival was 85% and 87%, respectively. Survival without graft loss at 1 year was 93% vs. 90%; at 3 years, 84% vs. 81%. Rejection rates were similar at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer did not differ significantly between groups. HIV breakthrough infection occurred more frequently among recipients of kidneys from donors with HIV (incidence rate ratio 3.14; 95% CI, 1.02 to 9.63), primarily due to nonadherence to antiretroviral therapy; viral suppression was regained in all cases. One potential HIV superinfection occurred without clinical consequences.
Conclusions: Kidney transplantation from donors with HIV to recipients with HIV was noninferior to transplantation from donors without HIV regarding safety outcomes, supporting the expansion of this practice from research to clinical care.
Implications for Practice: Expanding kidney transplantation involving donors and recipients with HIV to clinical practice could increase organ availability and reduce disparities in transplantation access for persons with HIV. Clinicians should monitor for HIV breakthrough infections and encourage adherence to antiretroviral therapy.
Study Strengths and Limitations: Strengths include a multicenter design and direct comparison groups. Limitations involve the observational design, inability to randomize due to allocation constraints, and heterogeneity in immunosuppression protocols.
Future Research: Further studies are needed to confirm these findings, evaluate long-term outcomes, and assess potential risks such as HIV superinfection.
RCT: MRI-Guided Biopsy Reduces Overdiagnosis of Clinically Insignificant Prostate Cancer
26 Sep, 2024 | 12:22h | UTCBackground: Overdiagnosis of clinically insignificant prostate cancer is a significant issue in population-based screening programs, primarily when prostate-specific antigen (PSA) testing is followed by systematic biopsy. Magnetic resonance imaging (MRI)-guided biopsies, which avoid systematic biopsies in men with negative MRI results, have shown potential in reducing unnecessary cancer diagnoses. However, long-term data are needed to confirm the safety and efficacy of this approach.
Objective: To evaluate whether MRI-targeted biopsies, when combined with PSA screening, can reduce the detection of clinically insignificant prostate cancer without compromising the identification of clinically significant or advanced disease.
Methods: This population-based, randomized trial in Sweden (GÖTEBORG-2) enrolled 13,153 men aged 50-60 years who underwent PSA screening. Men with PSA levels ≥3 ng/mL were randomized into two groups: (1) MRI-targeted biopsy only in cases with suspicious lesions, or (2) systematic biopsy in all cases with PSA elevation. Screening occurred every 2, 4, or 8 years depending on PSA levels, with follow-up for up to four years. The primary outcome was the detection of clinically insignificant prostate cancer, and secondary outcomes included clinically significant and advanced or high-risk prostate cancer.
Results: After a median follow-up of 3.9 years, the detection of clinically insignificant prostate cancer was significantly lower in the MRI-targeted biopsy group (2.8%) compared to the systematic biopsy group (4.5%), with a relative risk (RR) of 0.43 (95% CI, 0.32-0.57; P < 0.001). The relative risk of detecting clinically significant cancer was 0.84 (95% CI, 0.66-1.07), indicating no significant difference between the two groups. Advanced or high-risk cancers were detected in 15 men in the MRI group and 23 men in the systematic group (RR, 0.65; 95% CI, 0.34-1.24). Severe adverse events occurred in five patients (three in the systematic biopsy group, two in the MRI-targeted biopsy group).
Conclusions: Omitting biopsies in men with negative MRI results substantially reduced the diagnosis of clinically insignificant prostate cancer without increasing the risk of missing clinically significant or advanced cancers. MRI-targeted biopsy strategies can effectively limit overdiagnosis while maintaining safety in screening programs.
Implications for Practice: MRI-targeted biopsies offer a promising strategy to reduce unnecessary cancer diagnoses and avoid overtreatment in prostate cancer screening. Clinicians should consider integrating MRI into prostate cancer screening algorithms, especially in cases with elevated PSA but no MRI-detected lesions. This approach may also decrease biopsy-related complications and patient anxiety.
Study Strengths and Limitations: Strengths of this trial include its population-based design, large sample size, and thorough follow-up. Limitations include its single-center setting in Sweden, which may limit generalizability to more diverse populations, and a modest participation rate of 50%.
Future Research: Further studies should assess the cost-effectiveness of widespread MRI use in prostate cancer screening and explore its utility in diverse populations. Investigations into novel biomarkers that could further refine patient selection for MRI-targeted biopsy are also warranted.
Summary: Perioperative Management of Patients Taking Direct Oral Anticoagulants
19 Sep, 2024 | 21:12h | UTCDirect oral anticoagulants (DOACs)—including apixaban, rivaroxaban, edoxaban, and dabigatran—are increasingly used for stroke prevention in atrial fibrillation and for treating venous thromboembolism. Effective perioperative management of DOACs is essential to minimize bleeding and thromboembolic risks during surgical and nonsurgical procedures. Below are practical recommendations focused on the perioperative management of patients taking DOACs, based on a recent JAMA review article.
Elective Surgical or Nonsurgical Procedures
Classify Bleeding Risk of Procedures:
- Minimal Risk:
- Minor dental procedures (e.g., cleaning, extractions)
- Minor dermatologic procedures (e.g., skin lesion removal)
- Cataract surgery
- Low to Moderate Risk:
- Endoscopic procedures without high-risk interventions
- Cholecystectomy
- Inguinal hernia repair
- High Risk:
- Major surgery (e.g., cancer surgery, joint replacement)
- Procedures involving neuraxial anesthesia
- Endoscopic procedures with high-risk interventions (e.g., large polyp removal)
DOAC Management Strategies:
- Minimal Bleeding Risk Procedures:
- Option 1: Continue DOACs without interruption.
- Option 2: For added safety, withhold the morning dose on the day of the procedure (especially for twice-daily DOACs like apixaban and dabigatran).
- Low to Moderate Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 1 day before the procedure.
- This allows approximately 2 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 1 day after the procedure, ensuring adequate hemostasis.
- Preoperative:
- High Bleeding Risk Procedures:
- Preoperative:
- Discontinue DOACs 2 days before the procedure.
- This allows approximately 4-5 half-lives for drug clearance.
- Postoperative:
- Resume DOACs 2-3 days after the procedure, based on bleeding risk and hemostasis.
- Preoperative:
Evidence Supporting These Strategies:
- The PAUSE study demonstrated that standardized interruption protocols without heparin bridging result in low rates of:
- Thromboembolism: 0.2%–0.4%
- Major Bleeding: 1%–2%
Postoperative DOAC Resumption:
- Assess surgical-site hemostasis before resuming DOACs.
- Delay resumption if there is ongoing bleeding or concerns about hemostasis.
- For high bleeding risk procedures, consider a longer delay (2–3 days).
Perioperative Heparin Bridging:
- Not recommended for patients on DOACs.
- Bridging increases bleeding risk without reducing thromboembolism.
- DOACs have rapid offset and onset, making bridging unnecessary.
Special Considerations
Patients with Impaired Renal Function:
- For CrCl 30–50 mL/min:
- Dabigatran: Extend preoperative discontinuation by an additional day.
- For CrCl <30 mL/min:
- Dabigatran is contraindicated.
- For other DOACs, consider extending discontinuation to 3–4 days before surgery.
Patients Undergoing Neuraxial Anesthesia:
- Discontinue DOACs for 3 days (apixaban, edoxaban, rivaroxaban) or 4 days (dabigatran) before the procedure.
- Minimizes risk of spinal or epidural hematoma.
Dental Procedures:
- Generally safe to continue DOACs.
- For added safety:
- Omit or delay the dose on the day of the procedure.
- Employ local hemostatic measures (e.g., tranexamic acid mouthwash).
Endoscopic Procedures:
- Low-risk procedures (e.g., diagnostic endoscopy without biopsy):
- Follow standard DOAC interruption for low to moderate bleeding risk.
- High-risk procedures (e.g., polypectomy of large polyps):
- Extend DOAC discontinuation by an additional day pre- and post-procedure.
Patients Unable to Resume Oral Medications Postoperatively:
- Use prophylactic low-molecular-weight heparin (LMWH) until oral intake is possible.
- Avoid therapeutic-dose LMWH due to bleeding risk.
Emergent, Urgent, or Semiurgent Procedures
Risks:
- Higher bleeding risk: Up to 23%
- Thromboembolism risk: Up to 11%
Management Strategies:
- Assess Time Since Last DOAC Dose:
- If within 48 hours, consider that significant anticoagulant effect may persist.
- Laboratory Testing (if available):
- DOAC Level Testing:
- ≥50 ng/mL: Consider using reversal agents.
- <50 ng/mL: May proceed without reversal agents.
- DOAC Level Testing:
- Use of Reversal Agents:
- For Dabigatran:
- Idarucizumab (5 g IV)
- For Factor Xa Inhibitors (apixaban, rivaroxaban, edoxaban):
- Andexanet alfa (dosing based on last dose timing and amount)
- Prothrombin Complex Concentrates (PCCs): If andexanet alfa is unavailable or contraindicated.
- For Dabigatran:
- Proceeding Without Testing:
- If testing is unavailable and last DOAC dose was within 48 hours, consider reversal agents.
- If >48 hours since last dose, may proceed without reversal.
Considerations:
- Reversal agents are expensive and may carry thrombotic risks.
- Use should be judicious, weighing risks and benefits.
- Consult hematology or thrombosis experts when possible.
Key Takeaways
- Elective Procedures:
- Utilize standardized protocols based on procedural bleeding risk.
- Routine preoperative DOAC level testing is unnecessary.
- Avoid heparin bridging.
- Emergent/Urgent Procedures:
- Reversal agents may be appropriate when significant DOAC levels are present.
- Decision to use reversal agents should consider bleeding risk, time since last dose, and availability of DOAC level testing.
- Patient Communication:
- Ensure patients understand the plan for DOAC interruption and resumption.
- Provide clear instructions regarding timing and dosing.
- Interdisciplinary Coordination:
- Collaborate with surgical teams, anesthesiologists, and pharmacists.
- Use electronic medical records and clinical decision support tools to enhance communication.
Conclusion
By applying standardized perioperative management protocols, clinicians can effectively balance the risks of bleeding and thromboembolism in patients taking DOACs who require surgical or nonsurgical procedures. These strategies simplify decision-making, avoid unnecessary interventions like heparin bridging, and promote patient safety.
RCT: Perioperative Durvalumab Plus Neoadjuvant Chemotherapy Improved Survival in Muscle-Invasive Bladder Cancer
18 Sep, 2024 | 15:22h | UTCBackground: Neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy is the standard treatment for cisplatin-eligible patients with muscle-invasive bladder cancer (MIBC). Despite this approach, approximately 50% of patients experience recurrence within 3 years. Combining immunotherapy with chemotherapy may enhance outcomes, and durvalumab, a PD-L1 inhibitor, has shown promise when added to chemotherapy in previous studies.
Objective: To evaluate whether perioperative durvalumab combined with neoadjuvant gemcitabine–cisplatin improves event-free survival (EFS) and overall survival (OS) compared to neoadjuvant chemotherapy alone in cisplatin-eligible patients with operable MIBC.
Methods: In the phase 3, open-label, randomized NIAGARA trial, 1063 cisplatin-eligible patients with MIBC (clinical stage T2-T4aN0-1M0) were randomized 1:1 to receive either perioperative durvalumab plus neoadjuvant gemcitabine–cisplatin followed by radical cystectomy and adjuvant durvalumab (durvalumab group, n=533) or neoadjuvant gemcitabine–cisplatin followed by radical cystectomy alone (comparison group, n=530). The primary endpoints were EFS and pathological complete response (pCR). The key secondary endpoint was OS.
Results: At a median follow-up of 42.3 months, the estimated EFS at 24 months was 67.8% (95% CI, 63.6–71.7) in the durvalumab group versus 59.8% (95% CI, 55.4–64.0) in the comparison group (hazard ratio [HR] for progression, recurrence, not undergoing cystectomy, or death, 0.68; 95% CI, 0.56–0.82; P<0.001). The estimated OS at 24 months was 82.2% (95% CI, 78.7–85.2) in the durvalumab group versus 75.2% (95% CI, 71.3–78.8) in the comparison group (HR for death, 0.75; 95% CI, 0.59–0.93; P=0.01). Grade 3 or 4 treatment-related adverse events occurred in 40.6% of patients in the durvalumab group and 40.9% in the comparison group. Radical cystectomy was performed in 88.0% of patients in the durvalumab group and 83.2% in the comparison group.
Conclusions: Perioperative durvalumab combined with neoadjuvant chemotherapy significantly improved event-free and overall survival compared to neoadjuvant chemotherapy alone in cisplatin-eligible patients with operable MIBC.
Implications for Practice: Adding perioperative durvalumab to neoadjuvant chemotherapy may represent a new option for cisplatin-eligible patients with MIBC, offering improved survival outcomes without increasing significant adverse events or delaying surgery.
Study Strengths and Limitations: Strengths include the large sample size and randomized, phase 3 design. Limitations encompass the open-label design and inability to isolate the effects of neoadjuvant versus adjuvant durvalumab. Additionally, the trial was conducted before the widespread use of adjuvant nivolumab, potentially affecting the generalizability of the results.
Future Research: Further studies are needed to delineate the relative contributions of neoadjuvant and adjuvant durvalumab and to explore biomarkers such as circulating tumor DNA to guide treatment decisions.
Deep Learning Model Noninferior to Radiologists in Detecting Clinically Significant Prostate Cancer at MRI – Radiology
10 Aug, 2024 | 21:31h | UTCStudy Design and Population: This retrospective study evaluated the performance of a deep learning (DL) model for detecting clinically significant prostate cancer (csPCa) using multiparametric MRI (mpMRI) images from 5215 patients (5735 examinations) with a mean age of 66 years. The study included patients who underwent prostate MRI between January 2017 and December 2019 at a single academic institution. The DL model was trained on T2-weighted, diffusion-weighted, and contrast-enhanced MRI sequences, with pathologic diagnosis as the reference standard.
Main Findings: The DL model achieved an area under the receiver operating characteristic curve (AUC) of 0.89 on the internal test set and 0.86 on an external test set, demonstrating noninferiority to radiologists, who had AUCs of 0.89 and 0.84, respectively. Additionally, the combination of the DL model and radiologists improved diagnostic performance (AUC of 0.89). Gradient-weighted class activation maps (Grad-CAMs) effectively localized csPCa lesions, overlapping with true-positive cases in 92% of internal test set and 97% of external test set cases.
Implications for Practice: The DL model showed comparable performance to experienced radiologists in detecting csPCa at MRI, suggesting its potential to assist radiologists in improving diagnostic accuracy and reducing interobserver variability. Future research should focus on integrating the model into clinical workflows and assessing its impact on biopsy targeting.
RCT: Impact of single PSA screening invitation on 15-year prostate cancer mortality – JAMA
25 May, 2024 | 19:01h | UTCStudy Design and Population: This study is a secondary analysis of the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP), which focused on the long-term effects of prostate-specific antigen (PSA) screening on prostate cancer mortality. It involved 415,357 men aged 50 to 69 years from 573 primary care practices across England and Wales. Participants were randomized to either receive a single invitation for a PSA screening or to a control group receiving standard practice without invitation. The follow-up period concluded on March 31, 2021, after a median duration of 15 years.
Main Findings: The intervention group, which received one PSA screening invitation, showed a prostate cancer mortality rate of 0.69% compared to 0.78% in the control group, translating to a rate ratio of 0.92 and demonstrating a statistically significant but modest reduction in death from prostate cancer. Additionally, the screening led to increased detection rates of low-grade and localized prostate cancer. However, there were no significant differences in detection of more advanced cancer stages between the two groups. All-cause mortality rates were similar across both groups.
Implications for Practice: While the introduction of a single PSA screening invitation was associated with a slight decrease in prostate cancer mortality over 15 years, the absolute reduction was small. These findings suggest that while PSA screening can detect cancer earlier, its impact on long-term survival is limited and should be weighed against the potential for overdiagnosis and overtreatment. Future strategies in prostate cancer screening might need to focus more on risk stratification and personalized screening approaches to maximize benefits and minimize unnecessary interventions.
Reference (link to abstract – $ for full-text):
AUA/ASCO/SUO Updated guidelines for muscle-invasive urothelial bladder cancer
1 May, 2024 | 21:40h | UTCThe 2024 update to the muscle-invasive bladder cancer (MIBC) guidelines provides a risk-assessed framework for the treatment of this high-risk patient group, which constitutes about 25% of all bladder cancer diagnoses. These guidelines, revised through the AUA amendment process, integrate new research findings from May 2020 to November 2023, involving a rigorous review of 3739 abstracts and 46 full-text articles. Key updates include refined protocols for neoadjuvant and adjuvant chemotherapy, radical cystectomy, and multi-modal bladder-preserving therapies. Recommendations are categorized based on evidence strength, ranging from high to low, and are supplemented by clinical principles and expert opinions in areas lacking robust data. This structured approach aims to enhance clinical outcomes by updating practitioners on optimal management strategies and emphasizing the need for ongoing research to refine these recommendations.
Reference (link to free full-text):
The Lancet Commission: Global projections and recommendations for managing the increasing burden of prostate cancer
27 Apr, 2024 | 18:42h | UTCThe Lancet Commission’s report on prostate cancer highlights the expected doubling of annual cases from 1.4 million in 2020 to 2.9 million by 2040, driven by demographic changes and increased life expectancy. This comprehensive analysis divides the issue into epidemiology, diagnostics, management of localized and advanced disease, emphasizing disparities between high-income countries (HICs) and low- and middle-income countries (LMICs). Key findings indicate that late diagnoses are common, particularly in LMICs, leading to worse outcomes. The Commission advocates for significant changes in the diagnostic pathways and increased use of current technologies tailored to available resources to improve outcomes. Education and awareness programs are recommended to facilitate early detection and shift the treatment paradigm from palliative to curative, focusing on surgery and radiotherapy. Without decisive action, the global mortality from prostate cancer is set to rise, highlighting the need for urgent interventions across all countries, with a special focus on underserved populations.
Reference:
Consensus Paper | Surgical video data use, structure, and exploration (for research in AI, quality improvement, and education)
9 Aug, 2023 | 15:20h | UTC
Guideline Synopsis | Diagnosis and management of priapism
21 Jul, 2023 | 13:47h | UTCDiagnosis and Management of Priapism – JAMA (free for a limited period)
Original Guideline: The Diagnosis and Management of Recurrent Ischemic Priapism, Priapism in Sickle Cell Patients, and Non-Ischemic Priapism: An AUA/SMSNA Guideline – Journal of Urology
Podcast | Hematuria pearls
19 Jul, 2023 | 14:19h | UTC#404 Hematuria with Dr. Derek Fine – The Curbsiders
RCT | Prostatic artery embolization improves symptoms more than combined medical therapy in BPH patients
18 Jul, 2023 | 13:34h | UTC
Systematic Review | Ethical perspectives on surgical video recording for patients, surgeons and society
11 Jul, 2023 | 13:44h | UTC
Podcast | Untangling catheter associated UTIs
10 Jul, 2023 | 13:21h | UTC#402 Don’t Get Caught with a CAUTI – The Curbsiders
Cohort Study | Incidence and risk factors of postoperative urinary retention after inguinal hernia repair
7 Jul, 2023 | 16:11h | UTCGlobal Incidence and Risk Factors Associated With Postoperative Urinary Retention Following Elective Inguinal Hernia Repair: The Retention of Urine After Inguinal Hernia Elective Repair (RETAINER I) Study – JAMA Surgery (link to abstract – $ for full-text)
RCT | Brachytherapy alone sufficient for intermediate-risk prostate cancer, no FFP improvement with additional EBRT
7 Jul, 2023 | 16:06h | UTCEffect of Brachytherapy With External Beam Radiation Therapy Versus Brachytherapy Alone for Intermediate-Risk Prostate Cancer: NRG Oncology RTOG 0232 Randomized Clinical Trial – Journal of Clinical Oncology (link to abstract – $ for full-text)
Review | Surgical treatment options for male stress urinary incontinence
7 Jul, 2023 | 16:03h | UTC
RCT | Substituting saline with balanced crystalloid solution reduces delayed graft function in kidney transplantation
30 Jun, 2023 | 14:56h | UTCSummary: The BEST-Fluids study was a pragmatic, multicentre, double-blind, randomized controlled trial carried out across 16 hospitals in Australia and New Zealand, aimed at comparing the use of balanced crystalloid solution (Plasma-Lyte 148) and saline in deceased donor kidney transplantation. The sample size comprised of 808 participants, who were either adults or children of any age, with the primary outcome defined as delayed graft function (DGF) occurring within 7 days post-transplantation.
Findings from the trial revealed that the balanced crystalloid group experienced less DGF than the saline group, with 121 out of 404 participants (30%) and 160 out of 403 participants (40%), respectively. This result yields an adjusted relative risk of 0.74 and an adjusted risk difference of 10.1%.
The study suggests that balanced crystalloid solution significantly reduces the incidence of DGF compared to saline. As no significant safety concerns were raised during the trial, the researchers recommend the use of balanced crystalloid solution as the standard-of-care intravenous fluid in deceased donor kidney transplantation. However, the study doesn’t indicate any significant differences in graft failure or mortality rates, which calls for further research.
Article: Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial – The Lancet (free registration required)
Guideline | Management of adrenal incidentalomas
23 Jun, 2023 | 13:33h | UTCRelated:
Investigation and assessment of adrenal incidentalomas – Clinical Medicine Journal
#377 Adrenal Incidentalomas with Dr. William Young – The Curbsiders
M-A | Increased risk of cognitive toxic effects and fatigue in prostate cancer treatment with second-generation antiandrogens
16 Jun, 2023 | 14:00h | UTCAssociation of Second-generation Antiandrogens With Cognitive and Functional Toxic Effects in Randomized Clinical Trials: A Systematic Review and Meta-analysis – JAMA Oncology (link to abstract – $ for full-text)
RCT | No change in delayed graft function with normothermic perfusion vs. cold storage in kidney transplants
13 Jun, 2023 | 14:00h | UTC
Commentary on Twitter
In an open-label, randomized controlled trial, normothermic machine perfusion of kidneys from donation after circulatory death was found to be feasible and safe but did not reduce the rate of delayed graft function compared to static cold storage. https://t.co/faaAzK3bpc pic.twitter.com/iL7Je7Z7jO
— Nature Medicine (@NatureMedicine) June 2, 2023