Tranexamic Acid During Radical Cystectomy: A Randomized Clinical Trial.

Importance: Among cancer surgeries, patients requiring open radical cystectomy have the highest risk of red blood cell (RBC) transfusion. Prophylactic tranexamic acid (TXA) reduces blood loss during cardiac and orthopedic surgery, and it is possible that similar effects of TXA would be observed during radical cystectomy. Objective: To determine whether TXA, administered before incision and for the duration of radical cystectomy, reduced the number of RBC transfusions received by patients up to 30 days after surgery. Design, Setting, and Participants: The Tranexamic Acid During Cystectomy Trial (TACT) was a double-blind, placebo-controlled, randomized clinical trial with enrollment between June 2013 and January 2021. This multicenter trial was conducted in 10 academic centers. A consecutive sample of patients was eligible if the patients had a planned open radical cystectomy for the treatment of bladder cancer. Intervention: Before incision, patients in the intervention arm received a loading dose of intravenous TXA, 10 mg/kg, followed by a maintenance infusion of 5 mg/kg per hour for the duration of the surgery. In the control arm, patients received indistinguishable matching placebo. Main Outcomes and Measures: The primary outcome was receipt of RBC transfusion up to 30 days after surgery. Results: A total of 386 patients were assessed for eligibility, and 33 did not meet eligibility. Of 353 randomized patients (median [IQR] age, 69 [62-75] years; 263 male [74.5%]), 344 were included in the intention-to-treat analysis. RBC transfusion up to 30 days occurred in 64 of 173 patients (37.0%) in the TXA group and 64 of 171 patients (37.4%) in the placebo group (relative risk, 0.99; 95% CI, 0.83-1.18). There were no differences in secondary outcomes among the TXA group vs placebo group including mean (SD) number of RBC units transfused (0.9 [1.5] U vs 1.1 [1.8] U; P = .43), estimated blood loss (927 [733] mL vs 963 [624] mL; P = .52), intraoperative transfusion (28.3% [49 of 173] vs 24.0% [41 of 171]; P = .08), or venous thromboembolic events (3.5% [6 of 173] vs 2.9% [5 of 171]; P = .57). Non-transfusion-related adverse events were similar between groups. Conclusions and Relevance: Results of this randomized clinical trial reveal that TXA did not reduce blood transfusion in patients undergoing open radical cystectomy for bladder cancer. Based on this trial, routine use of TXA during open radical cystectomy is not recommended. Trial Registration: ClinicalTrials.gov Identifier: NCT01869413.

Home-based exercise prehabilitation to improve disease-free survival and return to intended oncologic treatment after cancer surgery in older adults with frailty: a secondary analysis of a randomized trial.

BACKGROUND: Improving survivorship for patients with cancer and frailty is a priority. We aimed to estimate whether exercise prehabilitation improves disease-free survival and return to intended oncologic treatment for older adults with frailty undergoing cancer surgery. METHODS: We conducted a secondary analysis of the oncologic outcomes of a randomized trial of patients ≥ 60 yr of age with frailty undergoing elective cancer surgery. Participants were randomized either to a supported, home-based exercise program plus nutritional guidance or to usual care. Outcomes for this analysis were one-year disease-free survival and return to intended oncologic treatment. We estimated complier average causal effects to account for intervention adherence. RESULTS: We randomized 204 participants (102 per arm); 182 were included in our modified intention-to-treat population and, of these participants, 171/182 (94%) had complete one-year follow up. In the prehabilitation group, 18/94 (11%) died or experienced cancer recurrence, compared with 19/88 (11%) in the control group (hazard ratio [HR], 1.25; 95% confidence interval [CI], 0.66 to 2.34; P = 0.49). Return to intended oncologic treatment occurred in 24/94 (29%) patients the prehabilitation group vs 20/88 (23%) in the usual care group (HR, 1.53; 95% CI, 0.84 to 2.77; P = 0.16). Complier average causal effects directionally diverged for disease-free survival (HR, 0.91; 95% CI, 0.20 to 4.08; P = 0.90) and increased the point estimate for return to treatment (HR, 2.04; 95% CI, 0.52 to 7.97; P = 0.30), but in both cases the CIs included 1. CONCLUSIONS: Randomization to home-based exercise prehabilitation did not lead to significantly better disease-free survival or earlier return to intended oncologic treatment in older adults with frailty undergoing cancer surgery. Our results could inform future trials powered for more plausible effect sizes, especially for the return to intended oncologic treatment outcome. STUDY REGISTRATION: ClinicalTrials.gov ( NCT02934230 ); first submitted 22 August 2016.

RéSUMé: CONTEXTE: L'amélioration de la survie des personnes atteintes de cancer et de fragilité est une priorité. Nous avons cherché à estimer si la préadaptation physique améliore la survie sans maladie et le retour au traitement oncologique prévu pour les personnes âgées fragiles bénéficiant d'une chirurgie du cancer. MéTHODE: Nous avons effectué une analyse secondaire des issues oncologiques d'une étude randomisée de patient·es âgé·es de 60 ans ou plus atteint·es de fragilité bénéficiant d'une chirurgie carcinologique non urgente. Nous avons randomisé les personnes participantes à un programme d'exercice à domicile accompagné de conseils nutritionnels ou à recevoir les soins habituels. Les critères d'évaluation de cette analyse étaient la survie sans maladie à un an et le retour au traitement oncologique prévu. Nous avons estimé les effets moyens causaux d'observance pour tenir compte de l'adhérence à l'intervention. RéSULTATS: Nous avons randomisé 204 participant·es (102 par bras); 182 personnes ont été incluses dans notre population modifiée en intention de traiter et, parmi ces participant·es, 171/182 (94%) ont fait l'objet d'un suivi complet à un an. Dans le groupe préadaptation, 18/94 (11%) personnes sont décédées ou ont connu une récidive du cancer, contre 19/88 (11 %) dans le groupe témoin (rapport de risque [HR], 1,25; intervalle de confiance [IC] à 95%, 0.66 à 2.34; P = 0.49). Le retour au traitement oncologique prévu a eu lieu chez 24 patient·es sur 94 (29 %) dans le groupe préadaptation vs 20/88 (23 %) dans le groupe de soins habituels (RR, 1.53; IC 95%, 0.84 à 2.77; P = 0.16). Les effets moyens causaux d'observance ont divergé directionnellement pour la survie sans maladie (RR, 0.91; IC 95%, 0.20 à 4.08; P = 0.90) et augmenté l'estimation ponctuelle du retour au traitement (RR, 2.04; IC 95%, 0.52 à 7.97; P = 0.30), mais dans les deux cas, les IC comprenaient 1. CONCLUSION: La randomisation pour la préadaptation physique à domicile n'a pas entraîné d'amélioration significative de la survie sans maladie ou de retour plus précoce au traitement oncologique prévu chez les personnes âgées fragiles bénéficiant d'une chirurgie du cancer. Nos résultats pourraient éclairer de futures études alimentées par des tailles d'effet plus plausibles, en particulier pour le critère de retour prévu au traitement oncologique. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT02934230 ); première soumission le 22 août 2016.

Frailty and decisional regret after elective noncardiac surgery: a multicentre prospective cohort study.

BACKGROUND: Frailty is associated with morbidity and mortality after surgery. The association of frailty with decisional regret is poorly defined. Our objective was to estimate the association of preoperative frailty with decisional regret status in the year after surgery. METHODS: We conducted a secondary analysis of a prospective, multicentre cohort study of patients aged ≥65 years who underwent elective noncardiac surgery. Decisional regret about having undergone surgery was ascertained at 30, 90, and 365 (primary time point) days after surgery using a 3-point ordinal scale. Bayesian ordinal logistic regression was used to estimate the association of frailty with decisional regret, adjusted for surgery type, age, sex, and mental health conditions. Subgroup and sensitivity analyses were conducted. RESULTS: We identified 669 patients; 293 (43.8%) lived with frailty. At 365 days after surgery, the unadjusted odds ratio (OR) associating frailty with greater decisional regret was 2.21 (95% credible interval [CrI] 0.98-5.09; P(OR>1)=0.97), which was attenuated after confounder adjustment (adjusted OR 1.68, 95% CrI 0.84-3.36; P(OR>1)=0.93). Similar results were estimated at 30 and 90 days. Additional adjustment for baseline comorbidities and disability score substantially altered the OR at 365 days (0.89, 95% CrI 0.37-2.12; P(OR>1)=0.39). There was a high probability that surgery type was an effect modifier (non-orthopaedic: OR 1.90, 95% CrI 1.00-3.59; P(OR>1)=0.98); orthopaedic: OR 0.87, 95% CrI 0.41-1.91; P(OR>1)=0.36). CONCLUSIONS: Among older surgical patients, there appears to be a complex association with frailty and decisional regret, with substantial heterogeneity based on assumed causal pathways and surgery type. Future studies are required to untangle the complex interplay between these factors.

Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Development of the multivariate administrative data cystectomy model and its impact on misclassification bias.

BACKGROUND: Misclassification bias (MB) is the deviation of measured from true values due to incorrect case assignment. This study compared MB when cystectomy status was determined using administrative database codes vs. predicted cystectomy probability. METHODS: We identified every primary cystectomy-diversion type at a single hospital 2009-2019. We linked to claims data to measure true association of cystectomy with 30 patient and hospitalization factors. Associations were also measured when cystectomy status was assigned using billing codes and by cystectomy probability from multivariate logistic regression model with covariates from administrative data. MB was the difference between measured and true associations. RESULTS: 500 people underwent cystectomy (0.12% of 428 677 hospitalizations). Sensitivity and positive predictive values for cystectomy codes were 97.1% and 58.6% for incontinent diversions and 100.0% and 48.4% for continent diversions, respectively. The model accurately predicted cystectomy-incontinent diversion (c-statistic [C] 0.999, Integrated Calibration Index [ICI] 0.000) and cystectomy-continent diversion (C:1.000, ICI 0.000) probabilities. MB was significantly lower when model-based predictions was used to impute cystectomy-diversion type status using for both incontinent cystectomy (F = 12.75; p < .0001) and continent cystectomy (F = 11.25; p < .0001). CONCLUSIONS: A model using administrative data accurately returned the probability that cystectomy by diversion type occurred during a hospitalization. Using this model to impute cystectomy status minimized MB. Accuracy of administrative database research can be increased by using probabilistic imputation to determine case status instead of individual codes.

How Surgeons Think to Avoid Error: A Case Study of the Neurovascular Bundle Sparing During a Robotic Prostatectomy.

OBJECTIVE: To illustrate how experts efficiently navigate a "slowing down moment" to obtain optimal surgical outcomes using the neurovascular bundle sparing during a robotic prostatectomy as a case study. DESIGN: A series of semistructured interviews with four expert uro-oncologists were completed using a cognitive task analysis methodology. Cognitive task analysis, CTA, refers to the interview and extraction of a general body of knowledge. Each interview participant completed four 1 to 2-hour semistructured CTA interviews. The interview data were then deconstructed, coded, and analyzed using a grounded theory analysis to produce a CTA-grid for a robotic prostatectomy for each surgeon, with headings of: surgical steps, simplification maneuvers, visual cues, error/complication recognition, and error/complication management and avoidance. SETTING: The study took place at an academic teaching hospital located in an urban center in Canada. PARTICIPANTS: Four expert uro-oncologists participated in the study. RESULTS: Visual cues, landmarks, common pitfalls, and technique were identified as the 4 key components of the decision-making happening during a slowing down moment in the neurovascular bundle sparing during a robotic prostatectomy. CONCLUSION: The data obtained from the CTA is novel information identifying patterns and cues that expert surgeons use to inform their surgical decision-making and avoid errors. This decision-making knowledge of visual cues, landmarks, common pitfalls and techniques is also generalizable for other surgical subspecialties. Surgeon educators, surgical teaching programs and trainees looking to improve their decision-making skills could use these components to guide their educational strategies.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

The impact of robotic surgery access on the management of patients with clinical stage I kidney tumors.

INTRODUCTION: Robotic surgery is used in the treatment of kidney tumors. We aimed to determine if robotic access was associated with initial choice of management for patients with a clinical stage I kidney mass. METHODS: Patients with a clinical stage I kidney mass were identified from the Canadian Kidney Cancer information system (CKCis) cohort. Sites were classified by year and access to robotic surgery. Associations between robotic access and initial management were determined using logistic regression. Univariable and multivariable analyses were performed, adjusting for tumor size and stage, and presented as relative risks (RR ) or adjusted RR (aRR) and 95% confidence intervals (CI). RESULTS: Overall, 4160 patients were included. Among patients treated with surgery, the proportion of partial nephrectomy compared to radical nephrectomy was significantly higher in robotic sites (77.3% for robotic sites vs. 65.9% for non-robotic sites; RR 1.17, 95% CI 1.12-1.23, p<0.0001; aRR 1.12, 95% CI 1.08-1.17, p<0.0001). Patients receiving partial nephrectomy at sites with robotic access were more likely to receive a minimally invasive approach compared to patients at non-robotic sites (61.4% vs. 50.9%, RR 1.21, 95% CI 1.12-1.30; aRR 1.16, 95% CI 1.08-1.25, p<0.0001). The proportion of patients managed by active surveillance was not significantly different between robotic (405, 16.9%) and non-robotic (258, 14.7%) sites (RR 1.15, 95% CI 0.99-1.32; aRR 0.97, 95% CI 0.84-1.12). CONCLUSIONS: Access to robotic kidney surgery was associated with increased use of partial nephrectomy and minimally invasive partial nephrectomy. Use of active surveillance was similar at robotic and non-robotic institutions. Limitations of this study include lack of data on perioperative complications and cancer recurrence.

Yield of second-round MRI targeted ultrasound-guided fusion prostate biopsy after initial first-round targeted biopsy.

INTRODUCTION: We aimed to determine the yield of second-round magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy and factors that may predict eventual clinically significant (CS) prostate cancer (PCa) diagnosis. METHODS: From 2013 to 2021, 85 men underwent second-round MRI-US fusion biopsy of 92 lesions (47.8% [44/92] peripheral zone and 52.2% [48/92] transition zone). Patient age, prostate-specific antigen (PSA), PSA density (PSAD), size/location of lesions, ADC value, Prostate Imaging-Reporting and Data System (PI-RADS), and PRECISE scores were recorded and compared to histopathological diagnosis (International Society of Urological Pathology [ISUP] grade-group 1 PCa, CS PCa=ISUP grade group ≥2 PCa) using logistic regression. RESULTS: Mean patient age, PSA, and PSAD were 64±7 years, 8.5±7.0 ng/ml, and 0.17±0.11, respectively. Results from first-round targeted biopsy were 63% (58/92) negative and 37% (34/92) clinically insignificant (grade group 1) PCa. Overall, second-round targeted biopsy identified 25% (23/92) CS PCa (grade group 2, n=19; grade group 3, n=4). Considering only lesions with initial negative targeted-biopsy results (n=58), 21% (12/58; grade group 2, n=8; grade group 3, n=4) CS PCa and 13 grade group 1 PCa were diagnosed at second-round biopsy. There was no difference in PSA (p=0.564), size (p=0.595), location (p=0.293), or PI-RADS score (p=0.342) of lesions by eventual CS PCa diagnosis. PSAD (0.2±1.4 vs. 0.16±0.10, p=0.167), ADC (0.748±0.199 vs. 0.833±0.257, p=0.151), and PRECISE score (p<0.01) showed a trend towards association or association with eventual CS PCa diagnosis. CONCLUSIONS: Repeat second-round targeted MRI-US fusion biopsy yielded CS PCa diagnosis in the targeted biopsy specimen in approximately 20% of patients in our study. PRECISE score may be a useful marker to help predict which patients require second-round biopsy.