Prevalence and Natural History of Non-metastatic Castrate Resistant Prostate Cancer: A Population-Based Analysis.

PURPOSE: To determine the prevalence and natural history of nmCRPC prior to the adoption of novel androgen receptor axis-targeting therapies(ARAT). MATERIALS AND METHODS: This was a retrospective population-based cohort study of men with nmCRPC in Ontario, Canada between January 2007-March 2018. Patients with prostate cancer, castrate level of testosterone(<1.7nmol/L) and a PSA>2.0ng/mL with a subsequent rise>25% from the nadir, and without metastasis were included. Annual prevalence of nmCRPC was calculated. Crude time from nmCRPC to metastasis and all-cause death are presented as medians with interquartile range(IQR). Predictors of time from nmCRPC to death were compared using univariable and multivariable cox proportional hazard models. RESULTS: We identified 2045 patients with nmCRPC. Median age was 79(IQR:72-84). 984 patients(48.1%) received upfront hormonal therapy while 583(28.5%) received initial radiotherapy and 478(23.4%) underwent radical prostatectomy. Median time from primary treatment to nmCRPC was 6 years(IQR:3-10). The average annual prevalence of nmCRPC was 8% among men receiving ADT. Crude median time from nmCRPC to death was 37.6 months(IQR:22.1-55.4). Median time from nmCRPC to metastasis and metastasis to death was 20.0 and 8.3 months, respectively. Patients who had primary surgery experienced longer crude survival. Older patients, patients who had a higher PSA at nmCRPC, and patients with grade group 4 to 5 disease had a shorter time from nmCRPC to death. CONCLUSION: This is the largest population-level analysis of the prevalence and natural history of nmCRPC. The current study can be used as a historical cohort to compare how novel imaging modalities and ARAT impact prevalence and disease trajectory over time.

Mortality, Health Care Use, and Costs of Weaning Center Survivors and Matched Prolonged ICU Stay Controls.

BACKGROUND: Quantification of long-term survival, health care utilization, and costs of prolonged ventilator dependence informs patient/family decision-making, health care policy, and understanding of specialized weaning centers (SWCs) as alternate care models. Our objective was to compare survival trajectory, health care utilization, and costs of SWC survivors with a matched cohort of ≥ 21-d-stay ICU patients. METHODS: This was a retrospective longitudinal (12 y) case-control study linking to health administrative databases with matching on age, sex, Charlson comorbidity index, income quintiles, and days in ICU and hospital in preceding 12 months. RESULTS: We matched 201 SWC subjects to 201 prolonged ICU survivors (402-subject cohort); 42% had a Charlson score of > 4. Risk of death at 12 months was lower in SWC subjects (hazard ratio [HR] 0.70 [95% CI 0.54-0.91]) adjusting for length of hospital admission (HR 1.02 [95% CI 1.00-1.04]) and number of care location transfers (HR 0.84 [95% CI 0.75-0.93]). By follow-up end, more SWC subjects died, 149 (73%) versus 127 (62%). We found no difference in discharge to home. At 12 months, acute health care utilization was comparable for the entire cohort, except hospital readmission rates (median interquartile range [IQR] 2 [1-3) vs 1 [1-2] d). Median (IQR) cost 12 months after unit discharge was CAD $68,165 ($19,894-$153,475). 12-month costs were higher in the SWC survivors (CAD $82,874 [$29,942-$224,965] vs CAD $55,574 [$6,572-$128,962], P < .001). SWC survivors had higher community health care utilization. Regression modeling demonstrated cost was associated with stay and care transfers but not SWC admission. Over 12-y follow-up, health care utilization and costs were higher in SWC survivors. CONCLUSIONS: SWC admission may confer some medium-term survival advantage; however, this may be influenced by selection bias associated with admission criteria.

Real-World Cost-Effectiveness of Bevacizumab With First-Line Combination Chemotherapy in Patients With Metastatic Colorectal Cancer: Population-Based Retrospective Cohort Studies in Three Canadian Provinces.

Background. Real-world evidence can be a valuable tool when clinical trial data are incomplete or uncertain. Bevacizumab was adopted as first-line therapy for metastatic colorectal cancer (mCRC) based on significant survival improvements in initial clinical trials; however, survival benefit diminished in subsequent analyses. Consequently, there is uncertainty surrounding the cost-effectiveness of bevacizumab therapy achieved in practice. Objective. To assess real-world cost-effectiveness of first-line bevacizumab with irinotecan-based chemotherapy versus irinotecan-based chemotherapy alone for mCRC in British Columbia (BC), Saskatchewan, and Ontario, Canada. Methods. Using provincial cancer registries and linked administrative databases, we identified mCRC patients who initiated publicly funded irinotecan-based chemotherapy, with or without bevacizumab, in 2000 to 2015. We compared bevacizumab-treated patients to historical controls (treated before bevacizumab funding) and contemporaneous controls (receiving chemotherapy without bevacizumab), using inverse-probability-of-treatment weighting with propensity scores to balance baseline covariates. We calculated incremental cost-effectiveness ratios (ICER) using 5-year cost and survival adjusted for censoring, with bootstrapping to characterize uncertainty. We also conducted one-way sensitivity analysis for key drivers of cost-effectiveness. Results. The cohorts included 12,112 (Ontario), 1,161 (Saskatchewan), and 2,977 (BC) patients. Bevacizumab significantly increased treatment costs, with mean ICERs between $78,000 and $84,000/LYG (life-year gained) in the contemporaneous comparisons and $75,000 and $101,000/LYG in the historical comparisons. Reducing the cost of bevacizumab by 50% brought ICERs in all comparisons below $61,000/LYG. Limitations. Residual confounding in observational data may bias results, while the use of original list prices overestimates current bevacizumab cost. Conclusion. The addition of bevacizumab to irinotecan-based chemotherapy extended survival for mCRC patients but at significant cost. At original list prices bevacizumab can only be considered cost-effective with certainty at a willingness-to-pay threshold over $100,000/LYG, but price reductions or discounts have a significant impact on cost-effectiveness.

Hard-to-Reach Populations and Administrative Health Data: A Serial Cross-sectional Study and Application of Data to Improve Interventions for People Experiencing Homelessness.

BACKGROUND: Intervention studies with vulnerable groups in the emergency department (ED) suffer from lower quality and an absence of administrative health data. We used administrative health data to identify and describe people experiencing homelessness who access EDs, characterize patterns of ED use relative to the general population, and apply findings to inform the design of a peer support program. METHODS: We conducted a serial cross-sectional study using administrative health data to examine ED use by people experiencing homelessness and nonhomeless individuals in the Niagara region of Ontario, Canada from April 1, 2010 to March 31, 2018. Outcomes included number of visits; unique patients; group proportions of Canadian Triage and Acuity Scale (CTAS) scores; time spent in emergency; and time to see an MD. Descriptive statistics were generated with t tests for point estimates and a Mann-Whitney U test for distributional measures. RESULTS: We included 1,486,699 ED visits. The number of unique people experiencing homelessness ranged from 91 in 2010 to 344 in 2017, trending higher over the study period compared with nonhomeless patients. Rate of visits increased from 1.7 to 2.8 per person. People experiencing homelessness presented later with higher overall acuity compared with the general population. Time in the ED and time to see an MD were greater among people experiencing homelessness. CONCLUSIONS: People experiencing homelessness demonstrate increasing visits, worse health, and longer time in the ED when compared with the general population, which may be a burden on both patients and the health care system.

Assessment of Secondary Sarcomas Among Patients With Cancer of the Abdomen or Pelvis Who Received Combinations of Surgery, Radiation, and Chemotherapy vs Surgery Alone.

Importance: The association of radiation and chemotherapy with the development of secondary sarcoma is known, but the contemporary risk has not been well characterized for patients with cancers of the abdomen and pelvis. Objective: To compare the risk of secondary sarcoma among patients treated with combinations of surgery, radiation, or chemotherapy with patients treated with surgery alone and the general population. Design, Setting, and Participants: This population-based cohort study included 173 580 patients in Ontario, Canada, with nonmetastatic cancer of the prostate, bladder, colon, rectum or anus, cervix, uterus, or testis. Patients were enrolled from January 1, 2002, to January 31, 2017. Data analysis was conducted from March 1, 2019, to January 31, 2020. Exposures: Treatment combinations of radiation, chemotherapy, and surgery. Main Outcome and Measures: Diagnosis of sarcoma based on histologic codes from the Ontario Cancer Registry. Time to sarcoma was compared using a cause-specific proportional hazard model. Results: Of 173 580 patients, most were men (125 080 [72.1%]), and the largest group was aged between 60 and 69 years (58 346 [33.6%]). Most patients had genitourinary cancer (86 235 [51.4%]) or colorectal cancer (69 241 [39.9%]). Overall, 64 301 (37.1%) received surgery alone, 51 220 (29.5%) received radiation alone, 15 624 (9.0%) were treated with radiation and chemotherapy, 15 252 (8.8%) received radiation with surgery, and 11 822 (6.8%) received all 3 treatments. A total of 332 patients (0.2%) had sarcomas develop during a median (interquartile range) follow-up of 5.7 (2.2-8.9) years. The incidence of sarcoma was 0.3% among those who underwent radiation alone (138 of 51 220) and radiation with chemotherapy (40 of 15 624), 0.2% among those who received radiation and surgery (36 of 15 252) and all 3 modalities (25 of 11 822), and 0.1% among those who received surgery with chemotherapy (13 of 14 861) and surgery alone (80 of 64 801). Compared with a reference group of patients who had surgery alone, the greatest risk of sarcoma was found among patients who underwent a combination of radiation and chemotherapy (cause-specific relative hazard [csRH], 4.07; 95% CI, 2.75-6.01; P < .001), followed by patients who had radiation alone (csRH, 2.35; 95% CI, 1.77-3.12; P < .001), radiation with surgery (csRH, 2.33; 95% CI, 1.57-3.46; P < .001), and all 3 modalities (csRH, 2.27; 95% CI, 1.44-3.58; P < .001). In the general population, 7987 events occurred during 46 554 803 person-years (17.2 events per 100 000 person-years). The standardized incidence ratio for sarcoma among patients treated with radiation compared with the general population was 2.41 (95% CI, 1.57-3.69; 41.3 events per 100 000 person-years). The annual number of cases of sarcoma increased from 2009 (15 per 100 000 persons) to 2016 (32 per 100 000 persons), but the annual rate did not change during the study period. Conclusions and Relevance: In this cohort study, patients treated with radiation or chemotherapy for abdominopelvic cancers had an increased rate of sarcoma. Although the absolute rate is low, patients and physicians should be aware of this increased risk of developing sarcoma.

Rates of primary and secondary treatments for patients on active surveillance for localized prostate cancer-A population-based cohort study.

BACKGROUND: The rate of primary and secondary treatment while on active surveillance (AS) for localized prostate cancer at the general population level is unknown. Our objective was to determine the patterns of secondary treatments after primary surgery or radiation for patients who undergo AS. METHODS: This was a population-based retrospective cohort study of men aged 50-80 years old in Ontario, Canada, between 2008 and 2016. We identified 26 742 patients with prostate cancer, a Gleason grade score ≤7, and an index prostate-specific antigen ≤10 ng/mL. Patients were categorized as undergoing AS with or without delayed primary treatment (DT; treatment >6 months after diagnosis) versus immediate treatment (IT; treatment ≤6 months). Patients receiving DT and IT were propensity score matched and the rate of secondary treatment (surgery or radiation ± androgen deprivation treatment) was compared using Cox proportional hazards models. RESULTS: We identified 10 214 patients who underwent AS and 11 884 patients who underwent IT. Among patients undergoing AS, 3724 (36.5%) eventually underwent DT and among them, 406 (10.9%) underwent secondary treatment. The median time to DT was 1.2 years (IQR 0.5-8.1 years). The relative rate of undergoing secondary treatment was similar in the DT vs IT group (HR 0.92; 95% CI: 0.79-1.08). The risk of death in the DT group was higher compared to patients who did not undergo treatment (HR 1.23, 95% CI: 1.01-1.49). CONCLUSIONS: Among patients with localized prostate cancer on AS, one third undergo DT. The rate of secondary treatment was similar between the DT and IT groups. Patients in the DT group may experience a higher risk of mortality compared to those who remained on AS.

Temporal Trends and Predictors of Thirty-Day Readmissions and Emergency Department Visits Following Total Knee Arthroplasty in Ontario Between 2003 and 2016.

BACKGROUND: Total knee arthroplasty (TKA) is the second most common surgery performed in Canada. Understanding and improving quality metrics associated with such high-volume procedures is of utmost importance to maximize value within the healthcare system, which is a balance between cost and quality. Although rates and predictors of hospital readmission and emergency department (ED) visits following TKA have previously been described in privatized healthcare settings, few studies have evaluated trends in length of stay (LOS), hospital readmissions, and ED visits following TKA in a universal single-payer system. METHODS: Using data from a provincially held and validated registry, the Institute for Clinical and Evaluative Sciences, we undertook a review of all 205,152 TKAs performed in the province of Ontario, Canada, between 2003 and 2016. We determined temporal trends in utilization, LOS, readmissions, and ED visits and evaluated patient and provider predictors of hospital readmissions and ED visits using multivariate logistic regression modeling. We also grouped and described the most common reasons for readmission and ED visits based on the available International Classification of Diseases, Ninth Revision and Tenth Revision coding information. RESULTS: LOS decreased significantly over the study period (P < .0001), from a median of 5 days (10th percentile 3 days, 90th percentile 8 days) in 2003 to a median of 3 days (10th percentile 2 days, 90th percentile 4 days) in 2016. All-cause 30-day readmissions did not change significantly over the study period, but the rate of ED visits increased significantly over time. Predictors of 30-day readmission following TKA included older age, male gender, lower income quartile, not having a postoperative visit with a primary care physician (PCP), increased comorbidities, longer LOS, urgent or revision surgery, admission to a teaching hospital, and discharge to an inpatient rehabilitation facility. Variables that predicted increased odds of an ED visit included older age, male gender, lower income quartile, not having a postop visit with a PCP, increasing comorbidities, year of surgery, longer LOS, and revision surgery. Admission to a teaching hospital and discharge to an inpatient rehabilitation facility showed a trend toward increased odds of an ED visit. CONCLUSIONS: We identified a significant increase in ED visits following TKA in Ontario between 2003 and 2016, with no corresponding increase in hospital readmissions despite a significant temporal trend toward shorter LOS. Predictors of ED visits and readmissions were similar, including male gender, lower income, higher comorbidities, and lacking a PCP visit postoperatively. Increased rates of ED visits following TKA in Ontario represent a quality problem, as they are associated with increased cost to the public healthcare system without any substantial benefit. Interventions aimed at redirecting patients from the ED for minor postoperative concerns should be investigated, as this is likely to improve care by reducing costs, improving efficiency, and enhancing patient experience.

Complications after surgery for benign prostatic enlargement: a population-based cohort study in Ontario, Canada.

OBJECTIVES: To examine the complication rates after benign prostatic enlargement (BPE) surgery and the effects of age, comorbidity and preoperative medical therapy. DESIGN: A retrospective, population-based cohort study using linked administrative data. SETTING: Ontario, Canada. PARTICIPANTS: 52 162 men≥66 years undergoing first BPE surgery between 1 January 2003 to 31 December 2014. INTERVENTION: Medical therapy preoperatively and surgery for BPE. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome was overall 30-day postoperative complication rates. Secondary outcomes included BPE-specific event rates (bleeding, infection, obstruction, trauma) and non-BPE specific event rates (cardiovascular, pulmonary, thromboembolic and renal). Multivariable analysis examined the association between preoperative medical therapy and postoperative complication rates. RESULTS: The 30-day overall complication rate after BPE surgery was 2828 events/10 000 procedures and increased annually over the study period. Receipt of preoperative α-blocker monotherapy (relative rate (RR) 1.05; 95% CI 1.00 to 1.09; p=0.033) and antithrombotic medications (RR 1.27; 95% CI 1.22 to 1.31; p<0.0001) was associated with increased complication rates. Among the ≥80-year-old group, the rate of complications increased by 39% from 2003 to 2014 (RR 1.39; 95% CI 1.21 to 1.61; p<0.0001). The mean duration of medical and conservative management increased by a mean of 2.1 years between 2007 and 2014 (p<0.0001 for trend). CONCLUSIONS: Thirty-day complication rates after BPE surgery have increased annually between 2003 and 2014. Preoperative medical therapy with alpha blockers or antithrombotics was independently associated with higher rates of complications. Over this time, the duration of conservative therapy also increased.