The impact of the early COVID-19 pandemic on healthcare system resource use and costs in two provinces in Canada: An interrupted time series analysis.

INTRODUCTION: The aim of our study was to assess the initial impact of COVID-19 on total publicly-funded direct healthcare costs and health services use in two Canadian provinces, Ontario and British Columbia (BC). METHODS: This retrospective repeated cross-sectional study used population-based administrative datasets, linked within each province, from January 1, 2018 to December 27, 2020. Interrupted time series analysis was used to estimate changes in the level and trends of weekly resource use and costs, with March 16-22, 2020 as the first pandemic week. Also, in each week of 2020, we identified cases with their first positive SARS-CoV-2 test and estimated their healthcare costs until death or December 27, 2020. RESULTS: The resources with the largest level declines (95% confidence interval) in use in the first pandemic week compared to the previous week were physician services [Ontario: -43% (-49%,-37%); BC: -24% (-30%,-19%) (both p<0.001)] and emergency department visits [Ontario: -41% (-47%,-35%); BC: -29% (-35%,-23%) (both p<0.001)]. Hospital admissions declined by 27% (-32%,-23%) in Ontario and 21% (-26%,-16%) in BC (both p<0.001). Resource use subsequently rose but did not return to pre-pandemic levels. Only home care and dialysis clinic visits did not significantly decrease compared to pre-pandemic. Costs for COVID-19 cases represented 1.3% and 0.7% of total direct healthcare costs in 2020 in Ontario and BC, respectively. CONCLUSIONS: Reduced utilization of healthcare services in the overall population outweighed utilization by COVID-19 patients in 2020. Meeting the needs of all patients across all services is essential to maintain resilient healthcare systems.

Cost of Bladder Cancer Care: A Single-center Comparison of Radical Cystectomy and Trimodal Therapy.

INTRODUCTION: Radical cystectomy and trimodal therapy are both accepted options in the management of muscle-invasive bladder cancer. As such, we sought to evaluate the micro-level costs associated with both modalities. METHODS: All patients undergoing trimodal therapy or radical cystectomy for primary treatment of urothelial muscle-invasive bladder cancer at a single academic center between 2008 and 2012 were included. Direct costs associated with each phase of a patient's clinical course were collected from the hospital's financial department, and physician costs were calculated based on the provincial fee schedule. Costs of radiation treatments were derived from previously published literature. RESULTS: A total of 137 patients were included. The mean (±SD) patient age was 69 (±12) years. Overall, 89 (65%) patients underwent radical cystectomy and 48 (35%) were treated with trimodal therapy. The radical cystectomy group had higher rates of cT3/T4 compared to those in the trimodal therapy group (51% vs 26%, P < .001). The median cost in the treatment phase for radical cystectomy was $30,577 (IQR: $23,908-$38,837) vs $18,979 ($17,271-$23,519) for trimodal therapy (P < .001). There was no significant difference between treatment groups with respect to cost of diagnosis or workup. However, the cost of follow-up care was numerically higher for patients undergoing trimodal therapy compared to radical cystectomy ($3,096/y vs $1,974/y, P = .09). CONCLUSIONS: In appropriately selected patients with muscle-invasive bladder cancer trimodal therapy costs are not prohibitive and are lower than in radical cystectomy. With increasing follow-up time after primary treatment, the cost difference between modalities may be mitigated by the need for bladder surveillance and salvage therapy in the trimodal therapy cohort.

A Matched Analysis of Active Surveillance Versus Nephrectomy for T1a Small Renal Masses.

While patients with a small renal mass (SRM) on active surveillance (AS) experience excellent metastasis-free survival (MFS) and cancer-specific survival (CSS), differences in overall survival (OS) observed may be explained by selection of older/comorbid patients for AS. Few studies have evaluated AS versus primary intervention in clinically balanced groups. We identified patients aged 55-75 yr with an SRM (≤4 cm, T1a) in our institutional database (2000-2020). Patients from AS and nephrectomy subgroups were matched exactly for age, sex, Eastern Cooperative Oncology Group (ECOG) performance status, biopsy status, and histology. The primary outcomes were OS and an event-free survival (EFS) composite that included OS, CSS, MFS, progression, or systemic therapy, which we tested in Cox proportional-hazards models. We identified 377 patients (205 AS, 172 nephrectomy). The cohort was balanced after matching (n = 110; mean age 64 yr, 77% male, and 75% ECOG score 0). In each arm, 47% were biopsied (predominantly clear-cell histology). The predicted 5-yr OS was 96% for the nephrectomy group and 95% for the AS group (hazard ratio for nephrectomy vs AS [HR] 0.83, 95% confidence interval [CI] 0.13-5.32; p = 0.8), with corresponding 5-yr EFS rates of 93% and 96% (HR 1.88, 95% CI 0.35-10.15; p = 0.5). Among SRM cases well matched for age and overall health status, we observed higher 5-yr OS and EFS rates for AS than previously reported; the rates were not significantly different from those after nephrectomy. The matched characteristics of our population are similar to those for treatment arms in contemporary cohorts and the results support the safety of AS in younger, healthier patients. PATIENT SUMMARY: While it has been shown that active surveillance for small kidney tumors is safe in older and more frail patients, its safety in younger, healthier patients has not been confirmed. We compared outcomes for patients aged 55-75 yr who were managed with surgery or active surveillance, and were similar in age and overall health. The probability of death after 5 years was low overall and not significantly different between the groups, suggesting that active surveillance is safe in routine clinical practice.

Low-volume grade group 2 prostate cancer candidates for active surveillance: a radical prostatectomy retrospective analysis.

OBJECTIVE: Guidelines support considering selected men with ISUP grade group (GG) 2 prostate cancer for active surveillance (AS). We assessed the association of clinical variables with unfavorable pathology at radical prostatectomy in low-volume GG 2 prostate cancer on biopsy in a retrospective cohort. MATERIALS AND METHODS: This was a retrospective analysis of 378 men with low-volume (≤ 2 cores) GG 2 localized prostate cancer who underwent prostatectomy at a single tertiary cancer center. Multivariable logistic regression of unfavorable pathology, upgrading to ≥ T3, or GG ≥ 3 was performed in relation to clinical factors, common variables used in AS in GG 1 and percentage Gleason 4 at biopsy. We compared the performance of potential variables with commonly used combined AS restrictions in GG 1 prostate cancer. RESULTS: In total, 128/378 (34%) men had unfavorable pathology at radical prostatectomy. On multivariable analysis, > 5% Gleason pattern 4 was independently associated with an increased risk of GG ≥ 3. A maximum percentage core involvement > 50% was independently associated with an increased risk of pT-stage ≥ 3 and unfavorable pathology. Restriction to patients with ≤ 5% Gleason 4 decreased the upgrading of both unfavorable pathology (OR = 0.62, p = 0.041) and GG ≥ 3 (OR = 0.17, p = 0.0007) compared to the full cohort, while restriction to those with ≤ 50% of max core involvement did not. CONCLUSION: In low-volume GG 2, the percentage of Gleason 4 of ≤ 5% was the strongest predictor in reducing upgrading at final pathology. This easily available pathological descriptor could be used to guide urologists and patients when considering AS in this setting.

Initial health care costs for COVID-19 in British Columbia and Ontario, Canada: an interprovincial population-based cohort study.

BACKGROUND: COVID-19 imposed substantial health and economic burdens. Comprehensive population-based estimates of health care costs for COVID-19 are essential for planning and policy evaluation. We estimated publicly funded health care costs in 2 Canadian provinces during the pandemic's first wave. METHODS: In this historical cohort study, we linked patients with their first positive SARS-CoV-2 test result by June 30, 2020, in 2 Canadian provinces (British Columbia and Ontario) to health care administrative databases and matched to negative or untested controls. We stratified patients by highest level of initial care: community, long-term care, hospital (without admission to the intensive care unit [ICU]) and ICU. Mean publicly funded health care costs for patients and controls, mean net (attributable to COVID-19) costs and total costs were estimated from 30 days before to 120 days after the index date, or to July 31, 2020, in 30-day periods for patients still being followed by the start of each period. RESULTS: We identified 2465 matched people with a positive test result for SARS-CoV-2 in BC and 28 893 in Ontario. Mean age was 53.4 (standard deviation [SD] 21.8) years (BC) and 53.7 (SD 22.7) years (Ontario); 55.7% (BC) and 56.1% (Ontario) were female. Net costs in the first 30 days after the index date were $22 010 (95% confidence interval [CI] 19 512 to 24 509) and $15 750 (95% CI 15 354 to 16 147) for patients admitted to hospital, and $65 828 (95% CI 58 535 to 73 122) and $56 088 (95% CI 53 721 to 58 455) for ICU patients in BC and Ontario, respectively. In the community and long-term care settings, net costs were near 0. Total costs for all people, from 30 days before to 30 days after the index date, were $22 128 330 (BC) and $175 778 210 (Ontario). INTERPRETATION: During the first wave, we found that mean costs attributable to COVID-19 were highest for patients with ICU admission and higher in BC than Ontario. Reducing the number of people who acquire COVID-19 and severity of illness are required to mitigate the economic impact of COVID-19.

Androgen deprivation therapy for prostate cancer: Prescribing behaviors and preferences among urologists.

INTRODUCTION: Several androgen deprivation therapy (ADT) medications are available for treating advanced prostate cancer with roughly equivalent oncological efficacy and tolerability. We investigated the proportion of physicians who predominantly prescribe one type of ADT drug ("mono-prescriber") and assessed characteristics associated with prescription behavior. METHODS: Ontario men aged ≥65 years who were diagnosed with advanced prostate cancer (1997-2017) and initiated ADT thereafter for ≥3 consecutive months were identified using population-level administrative data. Their first prescription for injectable ADT was linked to a physician, and urologists with ≥10 prescriptions over the study period were included in the analysis (n=282). Urologists were classified as high mono-prescribers if ≥80% of their prescriptions were for one drug type. Multivariable logistic regression was used to examine the association of physician characteristics with the odds of being a high mono-prescriber. RESULTS: Overall, 67 (23.8%) of urologists were classified as high mono-prescribers but the frequency varied across health planning regions. The most commonly prescribed drugs and those used by mono-prescribers were goserelin (41.8% and 56.7%) and leuprolide (44.3% and 43.3%), respectively. In multivariable analysis, the odds of a physician being a high mono-prescriber were higher with more years in practice (odds ratio [OR] 1.06/year, 95% confidence interval [CI] 1.03-1.09, p<0.0001) and lower for higher patient volume (OR 0.33 for above vs. below median, 95% CI 0.17-0.63, p=0.0008). CONCLUSIONS: Overall, one in four urologists were classified as high mono-prescribers. Mono-prescribers had more years in practice and smaller volume practices, potentially suggesting habitual prescription behavior and/or the effect of external pressures.

"Bring the Hoses to Where the Fire Is!": Differential Impacts of Marginalization and Socioeconomic Status on COVID-19 Case Counts and Healthcare Costs.

OBJECTIVES: Local health leaders and the Director General of the World Health Organization alike have observed that COVID-19 "does not discriminate." Nevertheless, the disproportionate representation of people of low socioeconomic status among those infected resembles discrimination. This population-based retrospective cohort study examined COVID-19 case counts and publicly funded healthcare costs in Ontario, Canada, with a focus on marginalization. METHODS: Individuals with their first positive severe acute respiratory syndrome coronavirus 2 test from January 1, 2020 to June 30, 2020, were linked to administrative databases and matched to negative/untested controls. Mean net (COVID-19-attributable) costs were estimated for 30 days before and after diagnosis, and differences among strata of age, sex, comorbidity, and measures of marginalization were assessed using analysis of variance tests. RESULTS: We included 28 893 COVID-19 cases (mean age 54 years, 56% female). Most cases remained in the community (20 545, 71.1%) or in long-term care facilities (4478, 15.5%), whereas 944 (3.3%) and 2926 (10.1%) were hospitalized, with and without intensive care unit, respectively. Case counts were skewed across marginalization strata with 2 to 7 times more cases in neighborhoods with low income, high material deprivation, and highest ethnic concentration. Mean net costs after diagnosis were higher for males ($4752 vs $2520 for females) and for cases with higher comorbidity ($1394-$7751) (both P < .001) but were similar across levels of most marginalization dimensions (range $3232-$3737, all P ≥ .19). CONCLUSIONS: This study suggests that allocating resources unequally to marginalized individuals may improve equality in outcomes. It highlights the importance of reducing risk of COVID-19 infection among marginalized individuals to reduce overall costs and increase system capacity.

Cost-Effectiveness Analysis of Negative Pressure Wound Therapy to Prevent Surgical Site Infection After Elective Colorectal Surgery.

BACKGROUND: Surgical site infection is common after colorectal surgery and is associated with increased costs. Prophylactic negative pressure wound therapy has previously been shown to reduce surgical site infection compared with conventional dressings. However, negative pressure wound therapy application is met with hesitancy because of its additional cost. OBJECTIVE: This study aims to determine whether the application of prophylactic negative pressure wound therapy after elective colorectal surgery is cost-effective. DESIGN: A cost-effectiveness analysis comparing prophylactic negative pressure wound therapy versus conventional dressing was completed using a Markov microsimulation model. A publicly funded single health care payer perspective was adopted across a lifetime horizon. SETTING: This study was conducted using in-hospital elective colorectal surgery. PATIENTS: The base case was an age-, sex-, and comorbidity-standardized patient undergoing open elective colorectal surgery. INTERVENTION: Negative pressure wound therapy was applied postoperatively over closed incisions. MAIN OUTCOMES: The primary outcomes of interest were the number of surgical site infections, total costs, and quality-adjusted life-years gained. Secondary outcomes included emergency department presentation, hospital readmission, nursing wound care utilization, fascial dehiscence, incisional hernia, and non-surgical site infection-related complications. RESULTS: We found that prophylactic negative pressure wound therapy, standardized to 1000 patients, prevented 51 surgical site infections, 3 fascial dehiscences, 10 incisional hernias, 22 emergency department presentations, and 6 hospital readmissions. This resulted in a total cost saving of $17,066 and 92.2 quality-adjusted life-years gained ($17.07 and 0.09 quality-adjusted life-years gained on average per patient). When the patients' risk of surgical site infections was greater than 3.2%, negative pressure wound therapy was a cost-effective strategy at a willingness to pay of $50,000/quality-adjusted life-years. LIMITATIONS: We did not model for societal perspective, emergent presentations of incarcerated hernias, or complications with hernia repair. The results of this model are reliant on the published negative pressure wound therapy efficacy and may change when additional data arise. CONCLUSION: The use of negative pressure wound therapy is the dominant strategy with improved outcomes and reduced costs compared with conventional dressing in patients undergoing colorectal surgery, particularly in at-risk patients. See Video Abstract at http://links.lww.com/DCR/B782. ANLISIS DE RENTABILIDAD DE LA TERAPIA DE PRESIN NEGATIVA PARA PREVENIR INFECCIN DEL SITIO QUIRRGICO DESPUS DE CIRUGA COLORRECTAL ELECTIVA: ANTECEDENTES:La infección del sitio quirúrgico es común después de la cirugía colorrectal y se asocia con un aumento de los costos. Anteriormente se demostró que la terapia profiláctica con presión negativa reduce la infección del sitio quirúrgico en comparación con los apósitos convencionales. Sin embargo, el uso de la terapia de presión negativa se encuentra en dudas debido a su costo adicional.OBJETIVO:Determinar si la aplicación de la terapia profiláctic con presión negativa después de la cirugía colorrectal electiva es rentable.DISEÑO:Se completó un análisis de costo-efectividad comparando la terapia profiláctica con presión negativa versus apósito convencional utilizando un modelo de microsimulación de Markov. Se adoptó una perspectiva de pagador único de asistencia sanitaria financiada con fondos públicos a lo largo de toda la vida.AJUSTE:Cirugía colorrectal electiva intrahospitalaria.PACIENTES:El caso base fue un paciente estandarizado por edad, sexo y comorbilidad sometido a cirugía colorrectal abierta electiva.INTERVENCIÓN:Aplicación postoperatoria de terapia de presión negativa sobre incisiones cerradas.RESULTADOS PRINCIPALES:Los resultados primarios de interés fueron el número de infecciones del sitio quirúrgico, los costos totales y los años de vida ganados ajustados por calidad. Los resultados secundarios incluyeron presentación en la sala de emergencias, reingreso al hospital, la utilización del cuidado de heridas por enfermería, dehiscencia fascial, hernia incisional y complicaciones relacionadas con infecciones del sitio no quirúrgico.RESULTADOS:Estandarizado para 1,000 pacientes, encontramos que la terapia profiláctica con presión negativa previno 51 infecciones del sitio quirúrgico, 3 dehiscencias fasciales, 10 hernias incisionales, 22 presentaciones en la sala de emergencias y 6 reingresos al hospital. Esto resultó en un ahorro total de costos de $ 17.066 y 92.2 años de vida ganados ajustados por calidad ($ 17.07 y 0.09 años de vida ganados ajustados por calidad en promedio por paciente). Cuando el riesgo de infección del sitio quirúrgico de los pacientes era superior al 3,2%, la terapia de presión negativa era una estrategia rentable con una disposición a pagar de 50.000 dólares por años de vida ajustados por calidad.LIMITACIONES:No modelamos para la perspectiva social, presentaciones emergentes de hernias encarceladas o complicaciones con la reparación de hernias. Los resultados de este modelo dependen de la eficacia publicada de la terapia de presión negativa y pueden cambiar cuando surjan más datos.CONCLUSIONES:El uso de la terapia de presión negativa es la estrategia dominante con mejores resultados y costos reducidos en comparación con el apósito convencional en pacientes sometidos a cirugía colorrectal, particularmente en pacientes de riesgo. Consulte Video Resumen en http://links.lww.com/DCR/B782. (Traducción- Dr. Francisco M. Abarca-Rendon).

A Population-based Study Comparing Outcomes for Patients With Metastatic Castrate Resistant Prostate Cancer Treated by Urologists or Medical Oncologists With First Line Abiraterone Acetate or Enzalutamide.

OBJECTIVES: To compare toxicity and all-cause mortality for mCRPC patients receiving first line oral systemic therapy prescribed by medical oncologists and urologists. METHODS: Population-based retrospective cohort study of chemotherapy-naïve men aged ≥66 years treated for mCRPC with first-line abiraterone or enzalutamide based on administrative health data (Ontario, Canada, 2012-2017). Primary outcomes were hospitalizations/ER visits for any cause or treatment-related toxicity during first-line mCRPC treatment. Secondary outcome was all-cause mortality. We calculated hazard ratios (HRs) comparing outcomes for different medical specialties using multivariable Cox proportional hazards models. RESULTS: Among 3405 mCRPC patients, 2407 (70.7%) received abiraterone and 998 (29.3%) received enzalutamide. 1786 (52.5%) patients visited the ER or were hospitalized. Men treated by medical oncologists had an increased risk of hospitalization/ER visits (HR1.16, 95%CI 1.03-1.31; P = .02), toxicity-related visits (HR1.34, 95%CI 1.08-1.69; P = .01), and mortality (HR1.16, 95%CI 1.02-1.33; P = .02) compared to urologists. Limited information was available, beyond PSA adjustment and prior treatment, on patient disease burden. CONCLUSION: We observed fewer hospital visits overall and for treatment-related toxicity for mCRPC patients who were prescribed first line abiraterone or enzalutamide by urologists compared to medical oncologists. These differences may result from higher prostate cancer disease burden in patients managed by medical oncologists, and/or other unmeasured differences in patient management between specialties.

Neoadjuvant Versus Adjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Microsimulation Model.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is clinically understudied, and there are no definitive recommendations regarding timing of perioperative chemotherapy. The objective of this study was to compare 3 treatment pathways in UTUC: nephroureterectomy (NU) alone, neoadjuvant chemotherapy (NAC), and adjuvant chemotherapy (AC) using a microsimulation model. PATIENTS AND METHODS: An individual-level state transition model was constructed using TreeAgePro software to compare treatment strategies for patients with newly diagnosed UTUC. The base case was that of a 70-year-old patient with a radiographically localized upper tract tumor. Primary outcome was quality-adjusted life expectancy. Secondary outcomes included crude overall survival, rates of adverse events, and bladder cancer diagnoses. RESULTS: A total of 100,000 patients were simulated. NAC was preferred, with an estimated quality-adjusted life expectancy of 7.50 years versus 6.79 years with NU alone and 7.23 years with AC. Median crude overall survival was 123 months with NAC, 96 months with NU only, and 111 months with AC. Overall, 40.0% of patients in the AC group with invasive pathology completed chemotherapy. In the NAC group, 83.3% of patients completed chemotherapy. In the NAC group, 37.5% of patients experienced an adverse chemotherapy event compared to 15.1% of patients in the AC group. Bladder cancer recurrence rates were 64.9%, 65.9%, and 67.4% over the patient's lifetime for the NU, NAC, and AC strategies, respectively. CONCLUSION: This study supports the increased use of NAC in UTUC until robust randomized trials are completed. The ultimate choice should be based on patient and tumor factors.

Small Renal Mass Surveillance: Histology-specific Growth Rates in a Biopsy-characterized Cohort.

BACKGROUND: Most reports of active surveillance (AS) of small renal masses (SRMs) lack biopsy confirmation, and therefore include benign tumors and different subtypes of renal cell carcinoma (RCC). OBJECTIVE: We compared the growth rates and progression of different histologic subtypes of RCC SRMs (SRMRCC) in the largest cohort of patients with biopsy-characterized SRMs on AS. DESIGN, SETTING, AND PARTICIPANTS: Data from patients in a multicenter Canadian trial and a Princess Margaret cohort were combined to include 136 biopsy-proven SRMRCC lesions managed by AS, with treatment deferred until progression or patient/surgeon decision. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Growth curves were estimated from serial tumor size measures. Tumor progression was defined by sustained size ≥4 cm or volume doubling within 1 yr. RESULTS AND LIMITATIONS: Median follow-up for patients who remained on AS was 5.8 yr (interquartile range 3.4-7.5 yr). Clear cell RCC SRMs (SRMccRCC) grew faster than papillary type 1 SRMs (0.25 and 0.02 cm/yr on average, respectively, p = 0.0003). Overall, 60 SRMRCC lesions progressed: 49 (82%) by rapid growth (volume doubling), seven (12%) increasing to ≥4 cm, and four (6.7%) by both criteria. Six patients developed metastases, and all were of clear cell RCC histology. Limitations include the use of different imaging modalities and a lack of central imaging review. CONCLUSIONS: Tumor growth varies between histologic subtypes of SRMRCC and among SRMccRCC, which likely reflects individual host and tumor biology. Without validated biomarkers that predict this variation, initial follow-up of histologically characterized SRMs can inform personalized treatment for patients on AS. PATIENT SUMMARY: Many small kidney cancers are suitable for surveillance and can be monitored over time for change. We demonstrate that different types of kidney cancers grow at different rates and are at different risks of progression. These results may guide better personalized treatment.

Canadian Update on Surgical Procedures (CUSP) Urology Group consensus for intraoperative hemostasis during minimally invasive partial nephrectomy.

INTRODUCTION: Partial nephrectomy remains the gold standard in the management of small renal masses. However, minimally invasive partial nephrectomy (MIPN) is associated with a steep learning curve, and optimal, standardized techniques for time-efficient hemostasis are poorly described. Given the relative lack of evidence, the goal was to describe a set of actionable guiding principles, through an expert working panel, for urologists to approach hemostasis without compromising warm ischemia or oncological outcomes. METHODS: A three-step modified Delphi method was used to achieve expert agreement on the best practices for hemostasis in MIPN. Panelists were recruited from the Canadian Update on Surgical Procedures (CUSP) Urology Group, which represent all provinces, academic and community practices, and fellowship-and non-fellowship-trained surgeons. Thirty-two (round 1) and 46 (round 2) panellists participated in survey questionnaires, and 22 attended the in-person consensus meeting. RESULTS: An initial literature search of 945 articles (230 abstracts) underwent screening and yielded 24 preliminary techniques. Through sequential survey assessment and in-person discussion, a total of 11 strategies were approved. These are temporally distributed prior to tumor resection (five principles), during tumor resection (two principles), and during renorrhaphy (four principles). CONCLUSIONS: Given the variability in tumor size, depth, location, and vascularity, coupled with limitations of laparoscopic equipment, achieving consistent hemostasis in MIPN may be challenging. Despite over two decades of MIPN experience, limited evidence exists to guide clinicians. Through a three-step Delphi method and rigorous iterative review with a panel of experts, we ascertained a guiding checklist of principles for newly beginning and practicing urologists to reference.

Abiraterone vs. docetaxel for metastatic hormone-sensitive prostate cancer: A microsimulation model.

INTRODUCTION: Our aim was to determine whether androgen deprivation therapy (ADT) with abiraterone acetate (AA) or ADT with docetaxel chemotherapy (DC) resulted in improved quality-adjusted life years (QALYs) among men with de novo metastatic castration-sensitive prostate cancer (mCSPC) and the cost effectiveness of the preferred strategy using decision analytic techniques. METHODS: A microsimulation model with a lifetime time horizon was constructed. Our primary outcome was QALYs. Secondary outcomes included cost, incremental cost effectiveness ratio (ICER), unadjusted overall survival (OS), rates of second- and third-line therapy, and adverse events. A systematic literature review was used to generate probabilities and utilities to populate the model. The base case was a 65-year-old patient with de novo mCSPC. RESULTS: A total of 100 000 microsimulations were generated. Initial AA resulted in a gain of 0.45 QALYs compared to DC (3.36 vs. 2.91 QALYs) with an ICER of $276 251.82 per QALY gained with initial AA therapy. Median crude OS was 51 months with AA and 48 months with DC. Overall, 46.6% and 42.6% of patients received second-line therapy and 8.7% and 7.9% patients received third-line therapy in the AA and DC groups, respectively. Grade 3/4 adverse events were experienced in 17.6% of patients receiving initial AA and 22.3% of patients receiving initial DC. CONCLUSIONS: Although ADT with AA results in a gain in QALYs and crude OS compared to DC, AA therapy is not a cost-effective treatment strategy to apply uniformly to all patients. The availability of AA as a generic medication may help to close this gap. The ultimate choice should be based on patient and tumor factors.

A narrative review of pelvic lymph node dissection in prostate cancer.

Pelvic lymph node dissection (PLND) is an important component in the staging and prognostication of prostate cancer. We performed a narrative review to assess the literature surrounding PLND: (I) the current guideline recommendations and contemporary utilization, (II) the calculation of patient-specific risk to perform PLND using available nomograms, (III) to review the extent of dissection, and its associated outcomes and complications. Due to the improved lymph node yield, better staging, and theoretical improvement in the control of micro-metastatic disease, guidelines have supported the use of (extended-) PLND in patients deemed to be at intermediate or high risk of lymph node involvement (often at a threshold of 5% on modern risk nomograms). However, in practice, real-world utilization of PLND varies considerably due to multiple reasons. Conflicting evidence persists with no clear oncological benefit to PLND, and a small, but important, risk of morbidity. Complications are rare, but include lymphoceles; thromboembolic events; and more rarely, obturator nerve, vascular, and ureteric injury. Furthermore, changing disease incidence and stage migration in the context of earlier detection overall have led to a decreased risk of nodal disease. The trade-offs between the benefits, harms, and risk tolerance/threshold must be carefully considered between each patient and their clinician.

Are there differences between de novo and secondary upper tract urothelial carcinoma tumours?

INTRODUCTION: Upper tract urothelial carcinoma (UTUC) accounts for <5% of all urothelial cancers. We aimed to ascertain the clinical differences between UTUC tumours presenting de novo (DnUTUC) and those presenting secondary (SUTUC) following a bladder cancer diagnosis. METHODS: Our institutional database was queried for all UTUC patients who were surgically treated with radical nephroureterectomy or ureterectomy between 2003 and 2017. Bladder recurrence and cancer-specific mortality were compared. To reduce the possible bias due to confounding variables obtained from a simple comparison of outcomes, DnUTUC patients were matched (for age, gender, tumour location, type of surgery, grade, TNM staging, presence of carcinoma in situ, and lymphovascular invasion) with propensity score to SUTUC patients. Bladder recurrence and cancer-specific mortality were assessed with Cox proportional hazards model. RESULTS: A total of 117 UTUC patients were identified: 80 with DnUTUC (68.4%) and 37 with SUTUC (31.6%). A greater proportion of males with SUTUC was demonstrated (89.2% vs. 68.8; p=0.02). In both groups, 67.5% of patients had high-grade disease, but SUTUC demonstrated a higher carcinoma in situ rate (43.2% vs. 25%; p=0.047). Univariate analysis demonstrated that the five-year bladder recurrence rate was trending to be higher in SUTUC (65.3% vs. 20.5%; p=0.099). In the Cox model, however, it was associated with increased bladder recurrence (hazard ratio [HR] 3.69; 95% confidence interval [CI] 1.68-8.09; p=0.001). Although univariate analysis demonstrated that SUTUC patients were more likely to die of their disease (30.6% vs. 9%; p=0.009), the multivariable Cox model did not demonstrate this association. The limitations of this study include its retrospective, single-centre design and relatively small cohort of patients. CONCLUSIONS: In this hypothesis-generating study, some evidence suggests that further research is needed to delineate differences between SUTUC and DnUTUC.

A narrative review and update on management following negative prostate biopsy.

PURPOSE OF REVIEW: Prostate cancer has traditionally been diagnosed using systematic transrectal ultrasound-guided biopsy. However, given the inherent nature of sampling, a negative biopsy does not exclude clinically significant prostate cancer (csPCa), and continued controversy exists in the optimal management following initial biopsy. Numerous avenues for evaluation include multiparametric MRI (mpMRI), use of molecular biomarkers, repeat biopsy, and observation. RECENT FINDINGS: mpMRI has shown promise in guiding further biopsy management: for individuals with identified target lesions, increased accuracy and detection using combination targeted and systematic sampling has been repeatedly demonstrated in the literature as an effective strategy. For those with negative MRIs and/or negative biomarker (blood, urinary, tissue) studies, increasing evidence has suggested that these individuals may be able to avoid biopsy altogether, albeit at a small risk of missing csPCa. Observation should be based on an individual's risk of csPCa versus their competing health risks, and saturation biopsy reserved for rare cases with high clinical suspicion. SUMMARY: Management following an initial negative prostate biopsy requires careful discussion with the patient, their risk tolerance, and threshold for intervention. Although subject to availability, mpMRI and molecular biomarkers may better risk stratify patients, identify target lesions, and in certain cases, spare biopsy altogether.

Active Surveillance in Small Renal Masses in the Elderly: A Literature Review.

CONTEXT: Small renal masses have become increasingly common due to widespread imaging; however, optimal management of these lesions in the elderly can be complex due to the competing risks of intervention, natural history of disease, patient comorbidities, and expectations. In the properly selected elderly patient, active surveillance remains an accepted and attractive treatment approach. OBJECTIVE: We completed a literature review of small renal masses (enhancing, <4cm, T1aN0M0 disease) in the elderly, aged ≥70 yr, aimed at identifying the utility of active surveillance in this population. The primary outcomes were conversion to active treatment while on active surveillance and cancer-specific mortality. Secondary outcomes included predictors of treatment, type of treatment performed (partial nephrectomy, radical nephrectomy, and ablation), progression to metastases, all-cause mortality, tumor growth rate, and demographic data including age and Charlson Comorbidity Index. EVIDENCE ACQUISITION: A comprehensive search of electronic databases (e.g., MEDLINE, EMBASE, SCOPUS, Web of Science, and the Cochrane Library) using search terms "small renal mass" OR "SRM", AND "elderly," "senior," "aging," "geriatric," OR "octogenarian" was completed. All randomized controlled trials, nonrandomized comparison studies, and case series were included and screened by the reviewers. All comparison studies included in the systematic review were assessed for methodological quality using the Cochrane Risk of Bias tools. EVIDENCE SYNTHESIS: Seventeen primary studies including 36495 patients met the inclusion criteria for the systematic review. All studies were retrospective institutional chart or the Surveillance, Epidemiology, and End Results database reviews. There was a low (4-26%) rate of conversion to active treatment for active surveillance in the identified studies over a follow-up interval of up to 91.5 mo. Overall mortality was substantial in this elderly cohort, with 15-51% of patients being deceased over the course of study follow-up; however, there was minimal cancer-specific mortality due to patients succumbing to alternative comorbid disease. In the future, patient comorbidity and biological age versus the natural history of the individualized tumor biology may play an increasing role in the discussion regarding treatment options and consideration of active surveillance. CONCLUSIONS: Active surveillance is an effective management strategy in the elderly population. Few patients required the conversion to active treatment and there was low cancer-specific mortality. The majority of patients who expired over the course of the identified studies succumbed to alternative disease. The goal of treatment strategies should include weighing patient-specific prognosis relative to their competing health risks and treatment goals against the natural history of disease and risks of intervention. PATIENT SUMMARY: In this review article, the authors examined the utility of active surveillance in the setting of a small localized renal mass in the elderly population. Despite being on surveillance, we found that cancer-specific outcomes were excellent, and overall mortality was often a result of comorbid disease. However, there is significant heterogeneity among elderly patients, and treatment approaches should be focused around patient-centered goals and prognosis.