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A response from the author of the article "Reporting trends and prognostic significance of lymphovascular invasion in muscle-invasive urothelial carcinoma: A population-based study" that was published in the previous issue, is presented.

Background: Identifying optimal chemotherapy (CT) utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of perioperative CT for muscle-invasive bladder cancer (MIBC)., Methods: The Ontario Cancer Registry and linked treated records were used to identify neoadjuvant and adjuvant CT rates among patients with MIBC during 2004-2013. Monte Carlo simulation was used to estimate the proportion of observed rate variation that could be due to chance alone. The criterion-based benchmarking approach was used to explore whether social and health-system factors were associated with CT rates. We also used the "pared-mean" approach to identify a benchmark population of hospitals with the highest treatment rates. Hospital CT rates were adjusted for case mix and simulated using a multi-level multivariable model and a parametric bootstrapping approach., Results: The study population included 2581 patients; perioperative CT was delivered to 31% (798/2581). Multivariate analysis showed that treatment was strongly associated with patient socioeconomic status and hospital teaching status. The benchmark rate was 36%. Unadjusted CT rates were significantly different across hospitals (range 0%-52%, P < .001). The unadjusted benchmark perioperative CT rate was 45% (95% CI 40%-50%); utilization rate in nonbenchmark hospitals was 28% (95% CI 26%-30%). When using simulated CT rates adjusted for case mix, the benchmark CT rate was 41% (95% CI 35%-47%) and the nonbenchmark hospital CT rate was 30% (95% CI 28%-32%). The simulation analysis suggested that the observed component of variation (38%) was outside the 95% CI (22%-28%) of what could be expected due to chance alone., Conclusions: There is significant systematic variation in perioperative CT rates for MIBC across hospitals in routine practice. The benchmark perioperative CT rate for MIBC is 36%-41%., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Identifying optimal chemotherapy utilization rates can drive improvements in quality of care. We report a benchmarking approach to estimate the optimal rate of adjuvant chemotherapy (ACT) for stage III colon cancer., Methods: The Ontario Cancer Registry and linked treated records were used to identify ACT utilization. Monte Carlo simulation was used to estimate the proportion of ACT rate variation that could be due to chance alone. The criterion-based benchmarking approach was used to explore whether socioeconomic or system-level factors were associated with ACT. We also used the "pared-mean" approach to identify a benchmark population of hospitals with the highest ACT rates., Results: The study population included 2801 patients; ACT was delivered to 66% (1861/2801). Monte Carlo simulation suggested that the observed component of variation (15.6%) in ACT rates was within the 95% CI (11.5%-17.3%) of what could be expected due to chance alone; the nonrandom component of ACT rate variation across hospitals was only 1.5%. There was no difference in hospital ACT rate by teaching status (P = .107), cancer center status (P = .362), or having medical oncology on site (P = .840). Unadjusted ACT rates varied across hospitals (range 44%-91%, P = .017). The unadjusted benchmark ACT rate was 81% (95%CI 76%-86%); utilization rate in non-benchmark hospitals was 65% (95%CI 63%-66%). However, after adjusting for case mix, the difference in ACT utilization between benchmark and non-benchmark populations was significantly smaller., Conclusions: We did not find any system-level factors associated with the utilization of ACT. Our results suggest that the observed variation in hospital ACT rate is not significantly different from variation due to chance alone. Using the "pared-mean" approach may significantly overestimate optimal treatment rates if case mix is not considered., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The use of data from the real world to address clinical and policy-relevant questions that cannot be answered using data from clinical trials is garnering increased interest. Indeed, data from cancer registries and linked treatment records can provide unique insights into patients, treatments and outcomes in routine oncology practice. In this Review, we explore the quality of real-world data (RWD), provide a framework for the use of RWD and draw attention to the methodological pitfalls inherent to using RWD in studies of comparative effectiveness. Randomized controlled trials and RWD remain complementary forms of medical evidence; studies using RWD should not be used as substitutes for clinical trials. The comparison of outcomes between nonrandomized groups of patients who have received different treatments in routine practice remains problematic. Accordingly, comparative effectiveness studies need to be designed and interpreted very carefully. With due diligence, RWD can be used to identify and close gaps in health care, offering the potential for short-term improvement in health-care systems by enabling them to achieve the achievable.

Introduction: Definitive treatment for muscle-invasive bladder cancer includes either cystectomy or radiotherapy (RT). We describe use of RT and radiation oncology (RO) referral patterns in the contemporary era., Methods: The Ontario Cancer Registry and linked records of treatment were used to identify all patients who received cystectomy or RT for bladder cancer from 1994-2013. Physician billing records were linked to identify RO consultation before radical treatment. Multilevel logistic regression models were used to examine patient factors and physician-level variation in referral to RO and use of RT., Results: A total of 7461 patients underwent cystectomy or RT for bladder cancer from 1994-2013; 5574 (75%) had cystectomy and 1887 (25%) had RT. Use of RT decreased from 43% (126/289) in 1994 to 23% (112/478) in 2008 and remained stable from 2009-2013 (23%, 507/2202). RO referral rate among all cases decreased from 46% (134/289) in 1994 to 30% (143/478) in 2008; however, the rates began to rise in the contemporary era from 31% (137/442) in 2009 to 37% (165/448) in 2013 (p=0.03). Patient factors associated with use of RT include older age, greater comorbidity, and geographic location. Surgeon-level factors associated with greater preoperative referral to RO include higher surgeon case volume and practicing in a teaching hospital., Conclusions: One-quarter of patients treated with curative intent therapy for bladder cancer receive RT. While referral rates to RO are increasing, future data will identify the extent to which this has altered practice. Collaborative efforts promoting multidisciplinary care and RO consultation before radical treatment are warranted.

Background: The planning of national radiotherapy (RT) services requires a thorough knowledge of the country's cancer epidemiology profile, the radiotherapy utilization (RTU) rates and a future projection of these data. Previous studies have established RTU rates in high-income countries., Methods: Optimal RTU (oRTU) rates were determined for nine middle-income countries, following the epidemiological evidence-based method. The actual RTU (aRTU) rates were calculated dividing the total number of new notifiable cancer patients treated with radiotherapy in 2012 by the total number of cancer patients diagnosed in the same year in each country. An analysis of the characteristics of patients and treatments in a series of 300 consecutive radiotherapy patients shed light on the particular patient and treatments profile in the participating countries., Results: The median oRTU rate for the group of nine countries was 52% (47-56%). The median aRTU rate for the nine countries was 28% (9-46%). These results show that the real proportion of cancer patients receiving RT is lower than the optimal RTU with a rate difference between 10-42.7%. The median percent-unmet need was 47% (18-82.3%)., Conclusions: The optimal RTU rate in middle-income countries did not differ significantly from that previously found in high-income countries. The actual RTU rates were consistently lower than the optimal, in particular in countries with limited resources and a large population., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Estimates of appropriate treatment rates are required for monitoring and improving access to cancer care. Optimal utilization rates for palliative radiotherapy (PRT) for patients with non-small cell lung cancer (NSCLC) remain undefined. We aim to estimate the appropriate PRT rate for the general NSCLC population., Materials and Methods: Ontario's population-based cancer registry identified patients with NSCLC who died of their disease between 2006 and 2010. Multivariate analysis identified factors affecting PRT use, enabling us to define a benchmark population with unimpeded access to PRT. Proportion of cases treated in the last 2 years of life (PRT 2y ) was standardized to overall population characteristics. Benchmarks were compared to province-wide PRT 2y rates., Results: Availability of RT at the diagnosing hospital was the dominant determinant of increased PRT utilization. Patients diagnosed at hospitals with on site RT were therefore designated the benchmark population. The standardized benchmark for PRT 2y was 56%, compared to the province-wide rate of 49%. The gap between actual and optimal rates varied across patient ages, treatment indications, and geographic regions., Conclusions: Approximately 56% of patients who die of NSCLC in Ontario need PRT, but many are never treated., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Use of chemotherapy for muscle-invasive bladder cancer (MIBC) is known to be low. To understand factors driving practice we use the Theoretical Domains Framework (TDF) to identify barriers and enablers of chemotherapy use., Methods: A convenience sample of Canadian urologists, medical oncologists (MOs), and radiation oncologists (ROs) participated in individual, semi-structured, one-hour telephone interviews. An interview guide was developed using the TDF to assess potential barriers and enablers of chemotherapy use. Interviews were recorded and transcribed. Two investigators independently identified barriers and enablers and assigned them to specific themes. Participant recruitment continued until saturation., Results: A total of 71 physicians were invited to participate and 34 (48%) agreed to be interviewed: 13 urologists, 10 MOs, and 11 ROs. We identified the following barriers to the use of chemotherapy (relevant TDF domains in parentheses): 1) belief that the benefits of chemotherapy are not clinically important (beliefs about consequences); 2) inadequate multidisciplinary collaboration (environmental context and resources); 3) absence of "champions" advocating the use of chemotherapy (social and professional role); and 4) a lack of organizational clarity/policy regarding the referral process (environmental context and resources). The predominant enablers identified included: 1) "champions" who believe in the value of chemotherapy (social and professional role); 2) urologists who refer all patients to MO (behavioural regulation; memory, attention, and decision-making); and 3) system-level factors, including automatic multidisciplinary referral (environmental context and resources)., Conclusions: We have identified several system-level factors associated with delivery of chemotherapy. Behaviour change interventions should optimize multidisciplinary care of patients with MIBC., Patient Summary: Despite the fact that chemotherapy before or after surgery improves survival of patients with bladder cancer, several studies have shown that many patients in routine practice are not treated. In this study, we identify important system-level and physician-level factors that must be considered in efforts to improve patient care.

Background: Clinical trials have shown that chemoradiotherapy (CRT) improves survival compared to radiation therapy (RT) alone in muscle-invasive bladder cancer. We describe uptake of CRT and comparative effectiveness in routine practice., Methods: Electronic treatment records were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with curative-intent RT in 1999-2013. Modified Poisson regression was used to analyze factors associated with use of CRT. Cox model and propensity score analyses were used to explore factors associated with cancer-specific (CSS) and overall survival (OS)., Results: 1192 patients underwent RT during 1999-2013; median age was 79. Use of CRT increased over time: 36% (124/341) in 1999-2003, 38% (153/399) in 2004-2008, 48% (217/452) in 2009-2013 (p = 0.001). Drug details were available for 82% (402/493) of CRT cases; the most common regimens were single-agent Cisplatin (57%, 230/402), single-agent Carboplatin (31%, 125/402) and 5-FU/Mitomycin (4%, 17/402). Factors associated with CRT include younger age (p < 0.001), lower comorbidity (p = 0.001), and geographic region (range 14-89%, p < 0.001). Five year CSS and OS among CRT cases were 45% (95%CI 39-51%) and 35% (95%CI 30-40%). On adjusted analyses CRT was associated with superior survival compared to RT (CSS HR 0.70, 95%CI 0.59-0.84; OS HR 0.74, 95%CI 0.64-0.85); results were consistent on propensity score analysis. There was significant improvement in survival of all RT-treated cases (irrespective or chemotherapy delivery) in 2009-2013 compared to 1999-2003 (CSS HR 0.77, 95%CI 0.61-0.97; OS HR 0.82, 95%CI 0.69-0.98)., Conclusion: CRT is associated with superior survival compared to RT alone and its uptake corresponded to improved survival among all RT-treated cases in the general population. Uptake of CRT varies widely by geographic region., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Purpose: The scope and effect of radiation oncology (RO) outreach activities within centralized radiotherapy (RT) systems is poorly defined. The purpose of this study was to describe the outreach activities of Ontario's regional cancer centres, and to explore the relationship between radiation oncology (RO) outreach clinics and rates of radiotherapy (RT) utilization at hospitals without RT on site (HWOS-RT)., Materials and Methods: Ontario RO centres' outreach activities were identified by semi-structured interview. A multivariate analysis determined the association between on-site RT facilities, or presence of RO clinic at HWOS-RT, and RT utilization within one year of diagnosis (RT 1Y ), for all patients diagnosed with cancer in Ontario in 2011-2012., Results: RO outreach varied widely by region. Of the largest 58 diagnosing hospitals, 14 had RT on-site, 19 had no RT but RO outreach clinic(s) and 25 had no RT or RO clinic. RT was used more frequently for patients diagnosed at hospitals with on-site RT compared to those at HWOS-RT (RT 1Y  = 35% vs. 29%, RR = 1.32 [95% CI 1.27-1.38]). For HWOS-RT, RT was used more frequently if there was an RO clinic (RT 1Y  = 31% vs. 29%, RR = 1.06 [95% CI 1.02-1.10])., Conclusions: RO outreach clinics were associated with a small but significant increase in RT utilization. There is opportunity to improve access to RT by optimizing the effectiveness of RO outreach., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background: Palliative chemotherapy for advanced bladder cancer is recommended in clinical practice guidelines because of the results achieved in clinical trials. However, real-world treatment and outcomes have not been well described. We report the treatment delivery and survival associated with palliative chemotherapy in routine clinical practice., Materials and Methods: The population-based Ontario Cancer Registry was linked to electronic records of treatment to identify all patients with bladder cancer treated with palliative chemotherapy in Ontario during 1994 to 2008. Treatment regimens were identified for those cases treated at regional cancer centers. Overall survival (OS) and cancer-specific survival (CSS) were determined from the start of palliative chemotherapy. A Cox proportional hazards model was used to identify the factors associated with OS and CSS., Results: The palliative chemotherapy regimen was identified for 710 patients with bladder cancer in Ontario during 1994 to 2008. Gemcitabine-cisplatin (Gem-Cis) was delivered to 37% (261 of 710), gemcitabine-carboplatin (Gem-Carbo) to 14% (96 of 710), and MVAC (methotrexate, vinblastine, Adriamycin, and cisplatin) to 8% (56 of 710). Other regimens were delivered to 42% of cases. The proportion of cases treated with Gem-Cis increased during the study period: 3% in 1994 to 1999, 32% in 2000 to 2003, and 52% in 2004 to 2008 (P < .001). The median survival and 5-year OS by regimen was 10 months and 16% for Gem-Cis, 7 months and 6% for Gem-Carbo, and 10 months and 13% for MVAC, respectively. Multivariate analysis controlling for age and comorbidity demonstrated improved survival for Gem-Cis and MVAC compared with Gem-Carbo (hazard ratio, 1.53; 95% confidence interval, 1.19-1.98)., Conclusion: The median survival associated with palliative chemotherapy for bladder cancer in routine practice is slightly inferior to the outcomes reported in clinical trials. However, consistent with the clinical trial results, a proportion of patients treated with palliative chemotherapy will achieve long-term survival. Gem-Carbo is associated with inferior survival compared with Gem-Cis and MVAC in routine practice., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Simultaneous resection of primary colorectal cancer (CRC) and synchronous liver metastases (LM) is gaining interest. We describe management and outcomes of patients undergoing simultaneous resection in the general population., Methods: All patients with CRC who underwent surgical resection of LM between 2002 and 2009 were identified using the population-based Ontario Cancer Registry and linked electronic treatment records. Synchronous disease was defined as having resection of CRCLM within 12 weeks of surgery for the primary tumour., Results: During the study period, 1310 patients underwent resection of CRCLM. Of these, 226 (17%) patients had synchronous disease; 100 (44%) had a simultaneous resection and 126 (56%) had a staged resection. For the simultaneous and the staged groups, the mean number of liver lesions resected was 1.6 and 2.3, respectively ( p < 0.001); the mean size of the largest lesion was 3.1 and 4.8 cm, respectively ( p < 0.001); and the major hepatic resection rate was 21% and 79%, respectively ( p < 0.001). Postoperative mortality for simultaneous cases at 90 days was less than 5%. Five-year overall survival and cancer-specific survival for patients with simultaneous resection was 36% (95% confidence interval [CI] 26%-45%) and 37% (95% CI 25%-50%), respectively. Simultaneous resections are common in the general population. A more conservative approach is being adopted for simultaneous resections by limiting the extent of liver resection. Postoperative mortality and long-term survival in this patient population is similar to that reported in other contemporary series., Conclusion: Compared with a staged approach, patients undergoing simultaneous resections had fewer and smaller liver metastases and underwent less aggressive resections. One-third of these patients achieved long-term survival.

Objective: To assess the use of pre-operative imaging for colon cancer and to identify factors associated with utilization in routine clinical practice., Methods: This population-based, retrospective cohort study used a random sample of 25% of colon cancer patients treated with surgery in the province of Ontario (2002-2008). Pre-operative imaging (<16 weeks from surgery) of the chest, abdomen-pelvis was identified. Modified poisson regression was used to analyze factors associated with practice patterns., Results: Of the 7,249 included patients, 48% had pre-operative imaging (CT abdomen and imaging of the chest) in keeping with guideline recommendations. The rate of guideline concordant pre-operative imaging increased over time: 64% in the most recent study period (2006-2008) versus 31% (2002-2004); P < 0.001. Variables associated with use of chest imaging: Age, co-morbidity, surgeon volume, and geographic region; no association with gender, hospital volume, or socio-economic status. Variables associated with use of abdomen imaging: Hospital volume and geographic region; no association with age, gender, comorbidity, socio-economic status, or surgeon volume., Conclusion: In clinical practice, the majority of patients were not receiving pre-operative imaging that was in line with clinical practice guidelines; however, use increased over time indicating a possible association with dissemination of clinical practice guidelines. J. Surg. Oncol. 2017;115:202-207. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: It is known that adjuvant chemotherapy improves survival in women with breast cancer. It is not known whether the interval between surgery and the initiation of chemotherapy influences its effectiveness., Purpose: To determine the relationship between time to initiation of adjuvant chemotherapy and survival in women with breast cancer, through a systematic review of the literature and meta-analysis., Methods: Systematic review of MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Database of Controlled Trials, Google Scholar, and abstracts presented at major international oncology conferences. The primary meta-analysis included only high-validity studies which directly measured the time from surgery to initiation of adjuvant chemotherapy and which controlled for major prognostic factors. Outcomes reported in the original studies were converted to a regression coefficient (β) and standard error corresponding to a 4-week delay in the initiation of chemotherapy. These relative risks were combined in both fixed- and random-effects models. Homogeneity was assessed by the Cochran χ 2 statistic and the I 2 statistic. Potential publication bias was investigated using standard error-based funnel plots., Results: Meta-analysis of 8 high-validity studies demonstrated that a 4-week increase in TTAC was associated with a significant increase in the risk of death in both the fixed-effects model (RR 1.04; 95 % CI, 1.01-1.08) and random-effects model (RR 1.08; 95 % CI, 1.01-1.15). The association remained significant when the most highly weighted studies were sequentially removed from this analysis, and also when additional, lower validity studies were included in this analysis. Funnel plots showed no significant asymmetry to suggest publication bias., Conclusions: Increased waiting time from surgery to initiation of adjuvant chemotherapy is associated with a significant decrease in survival. Avoidance of unnecessary delays in the initiation of adjuvant chemotherapy has the potential to save the lives of many women with breast cancer.

Purpose: Reasons for variable utilization of adjuvant chemotherapy (ACT) for colon cancer have not been well described. We report medical oncology (MO) referral patterns and subsequent use of ACT., Methods: Treatment records were linked to the population-based Ontario Cancer Registry to describe MO referral and ACT use among 5289 patients with stage II-III colon cancer treated in 2002-2008. Modified Poisson regression was used to analyze factors associated with MO referral and ACT use. Multilevel modeling was used to explore the proportion of variation in practice attributable to providers., Results: There was wide geographic variation in MO referral rates for stage II (range 37-80 %, p < 0.001) and stage III disease (range 77-98 %, p < 0.001). Use of ACT among referred patients varied across regions for stage II (range 12-49 %, p < 0.001) but not stage III (range 67-79 %, p = 0.353). For both stages, younger patients (p < 0.001) with less comorbidity (p < 0.010) were more likely to be referred to MO and treated with ACT. Applying the fitted regression model to nonreferred stage III patients suggests that 38 % had >50 % probability of having ACT if they had seen a MO. Among stage III patients, 15 % percent of the variance in MO referral rate and 6 % of the variance in ACT utilization rate is attributable to the surgeon and MO respectively., Conclusions: A substantial proportion of non-referred patients with stage III colon cancer may have been offered ACT if they had seen MO. A small proportion of variance in referral rate and ACT treatment is attributable to providers.

Background: Previous reports on the outcome of surgery for colorectal cancer lung metastases (CRCLM) have come from high-volume centers. This report describes the outcomes achieved in the general population of Ontario., Methods: All patients in Ontario who underwent resection of CRCLM between 1994 and 2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified surgical procedures and chemotherapy delivery. This report describes the volume of resections for CRCLM in relation to the incidence of colorectal cancer (CRC). Temporal trends in practice are described during three periods: 1994-1999, 2000-2004, and 2005-2009. Overall survival (OS) and cancer-specific survival (CSS) were measured from the time of lung resection., Results: A total of 709 patients underwent resection of CRCLM. Between 1994 and 2009, surgical volume increased 190 %, from 1 resection for every 282 incident cases to 1 resection for every 97 incident cases (p < 0.001). The use surgery for CRCLM varied considerably between regions, from 1 resection per 95 incident cases to 1 resection per 212 incident cases (p = 0.021). Use of perioperative chemotherapy increased during study periods, from 22 % (28/130) to 34 % (73/217) to 40 % (146/362; p < 0.001). Utilization rates varied across geographic regions (range 21-59 %; p = 0.005). The OS rate was 40 % [95 % confidence interval (CI) 36-44 %] at 5 years and 27 % (95 % CI 23-31 %) at 10 years. The CSS rate was 42 % (95 % CI 38-46 %) at 5 years and 32 % (95 % CI 27-37 %) at 10 years., Conclusions: A proportion of patients with resected CRCLM will achieve long-term survival. Outcomes in routine practice are comparable with those reported for high-volume centers. The use of surgery varies considerably across Ontario.

Objective: To test the hypotheses that: (i) use of preoperative imaging for muscle-invasive bladder cancer (MIBC) conforms to practice guidelines; (ii) preoperative imaging, through more accurate staging is associated with improved outcomes., Patient and Methods: In this population-based cohort study, records of treatment were linked to the Ontario Cancer Registry to identify all patients with MIBC treated with cystectomy from 1994 to 2008. Utilisation of chest, abdomen-pelvis and bone imaging were evaluated. Trends were evaluated over time. Logistic regression was used to analyse factors associated with utilisation. Cox model analyses were used to explore associations between imaging and survival., Results: In all, 2 802 patients with MIBC underwent cystectomy during 1994-2008. Over the three 5-year study periods there was an increase in the proportion of patients having preoperative: chest X-ray (55%, 64%, 63%, P < 0.001), computed tomography (CT) of the chest (10%, 10%, 21%, P < 0.001), bone scan (30%, 34%, 36%; P = 0.04) and CT/magnetic resonance imaging/ultrasonography abdomen/pelvis (80%, 87%, 90%, P ≤ 0.001). Use of chest imaging was associated with age (odds ratio [OR] 1.24-1.59 compared with the youngest age group), N-stage (OR 0.79 for the NX group compared with the N+ group), surgeon volume (OR 0.47-0.53 compared with the highest volume quartile) and geographic region (OR 0.47-2.19 compared with the largest region). Use of bone scan was associated with N-stage (OR 0.57 for the NX group compared with the N+ group) and geographic region (OR 0.71-1.34 compared with the largest region). In adjusted analyses, we found that patients who did not have preoperative chest imaging had inferior overall survival (OS), hazard ratio (HR) 1.12 (95% confidence interval [CI] 1.01-1.25) but not cancer specific survival (CSS), HR 1.09 (95% CI 0.97-1.22); those who did not have preoperative bone scan had inferior OS (HR 1.11, 95% CI 1.01-1.22) and CSS (HR 1.09, 95% CI 1.01-1.25). Survival in the abdomen and pelvis imaging group was not evaluated due to lack of a suitable control group., Conclusion: In routine clinical practice there is considerable variation in use of preoperative chest, body, and bone imaging. Preoperative chest and bone imaging is associated with improved outcomes; this association probably reflects better patient selection for cystectomy., (© 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.)

Purpose: Palliative radiation therapy (PRT) benefits many patients with incurable cancer, but the overall need for PRT is unknown. Our primary objective was to estimate the appropriate rate of use of PRT in Ontario., Methods and Materials: The Ontario Cancer Registry identified patients who died of cancer in Ontario between 2006 and 2010. Comprehensive RT records were linked to the registry. Multivariate analysis identified social and health system-related factors affecting the use of PRT, enabling us to define a benchmark population of patients with unimpeded access to PRT. The proportion of cases treated at any time (PRTlifetime), the proportion of cases treated in the last 2 years of life (PRT2y), and number of courses of PRT per thousand cancer deaths were measured in the benchmark population. These benchmarks were standardized to the characteristics of the overall population, and province-wide PRT rates were then compared to benchmarks., Results: Cases diagnosed at hospitals with no RT on-site and residents of poorer communities and those who lived farther from an RT center, were significantly less likely than others to receive PRT. However, availability of RT at the diagnosing hospital was the dominant factor. Neither socioeconomic status nor distance from home to nearest RT center had a significant effect on the use of PRT in patients diagnosed at a hospital with RT facilities. The benchmark population therefore consisted of patients diagnosed at a hospital with RT facilities. The standardized benchmark for PRTlifetime was 33.9%, and the corresponding province-wide rate was 28.5%. The standardized benchmark for PRT2y was 32.4%, and the corresponding province-wide rate was 27.0%. The standardized benchmark for the number of courses of PRT per thousand cancer deaths was 652, and the corresponding province-wide rate was 542., Conclusions: Approximately one-third of patients who die of cancer in Ontario need PRT, but many of them are never treated., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Importance: Surgical resection is standard treatment for patients with colorectal cancer (CRC) liver metastases (LM). Limited data describe practice and outcomes among elderly patients., Objective: To describe management and outcomes of surgical resection of CRC LM in elderly patients in routine practice., Design, Setting, and Participants: Population-based retrospective cohort study of routine clinical practices in the Canadian province of Ontario. All cases of CRC in Ontario who underwent resection of LM between January 1, 2002, and December 31, 2009, were identified using the population-based Ontario Cancer Registry and included in this study. Complete information about vital status in the Ontario Cancer Registry was available up to December 31, 2012; cause of death was available up to December 31, 2010. Final study analyses were performed March 13, 2015. Surgical resections of CRC LM were identified from hospital admission records. Pathology reports provided details regarding extent of disease and surgical procedure. Patients were classified into 3 age groups: younger than 65 years, 65 to 74 years, and 75 years or older. We describe volume of resected CRC LM as a ratio of incident cases per CRC LM resection. Use of perioperative chemotherapy was identified through linked electronic treatment and physician billing records. Preoperative and postoperative chemotherapy was defined as chemotherapy given within 16 weeks of surgery., Main Outcomes and Measures: Overall survival and cancer-specific survival measured from time of LM resection., Results: We identified 1310 patients: 710 (54%) younger than 65 years; 414 (32%) 65 to 74 years; and 186 (14%) 75 years or older. Case volumes of CRC LM resection varied substantially across age groups. For patients younger than 65 years, there was 1 resection per 26 incident cases; 65 to 74 years, 1 per 38; and 75 years or older, 1 per 101 (P<.001). Patients less than 65 years of age had a mean of 2.3 lesions; 65 to 74 years, 2.0; and 75 years or older, 1.6 (P<.001). For patients younger than 65 years, mean size of the largest lesion was 4.0 cm; patients 65 to 74 years, 4.4 cm; and 75 years or older, 4.5 cm (P=.04). The likelihood patients younger than 65 years were to undergo a major liver resection of more than 3 segments was 65%; 65 to 74 years, 65%; and 75 years or older, 42% (P=.04). The percentage of patients younger than 65 years who underwent perioperative chemotherapy was 71% (501 of 710); 65 to 74 years, 57% (237 of 414); and 75 years or older, 41% (77 of 186) (P<.001). The incidence of 90-day mortality for patients younger than 65 years was 2% (11 of 710); 65 to 74 years, 5% (20 of 414); and 75 years or older, 8% (14 of 186) (P<.001). Cancer-specific survival at 5 years for patients younger than 65 years of age was 49%; 65 to 74 years, 47%; and 75 years or older, 35% (P<.001). Overall survival for patients younger than 65 years was 49%; 65 to 74 years, 44%; and 75 years or older, 28% (P<.001)., Conclusions and Relevance: Resection of CRC LM is associated with greater risk of postoperative mortality among elderly patients despite less aggressive treatment. Although the long-term outcomes are inferior to younger patients, a substantial proportion of elderly patients will have long-term survival.

Purpose: Estimates of the appropriate rate of use of radiation therapy (RT) are required for planning and monitoring access to RT. Our objective was to compare estimates of the appropriate rate of use of RT derived from mathematical models, with the rate observed in a population of patients with optimal access to RT., Methods and Materials: The rate of use of RT within 1 year of diagnosis (RT1Y) was measured in the 134,541 cases diagnosed in Ontario between November 2009 and October 2011. The lifetime rate of use of RT (RTLIFETIME) was estimated by the multicohort utilization table method. Poisson regression was used to evaluate potential barriers to access to RT and to identify a benchmark subpopulation with unimpeded access to RT. Rates of use of RT were measured in the benchmark subpopulation and compared with published evidence-based estimates of the appropriate rates., Results: The benchmark rate for RT1Y, observed under conditions of optimal access, was 33.6% (95% confidence interval [CI], 33.0%-34.1%), and the benchmark for RTLIFETIME was 41.5% (95% CI, 41.2%-42.0%). Benchmarks for RTLIFETIME for 4 of 5 selected sites and for all cancers combined were significantly lower than the corresponding evidence-based estimates. Australian and Canadian evidence-based estimates of RTLIFETIME for 5 selected sites differed widely. RTLIFETIME in the overall population of Ontario was just 7.9% short of the benchmark but 20.9% short of the Australian evidence-based estimate of the appropriate rate., Conclusions: Evidence-based estimates of the appropriate lifetime rate of use of RT may overestimate the need for RT in Ontario., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Despite clinical evidence and recommendations from international treatment guidelines, the use of perioperative chemotherapy for muscle-invasive bladder cancer in routine practice remains low. Although multiple studies have described underutilization, there is an urgent need to better understand the elements contributing to the observed gaps in care. In this commentary, we explore what is known about the factors contributing to underutilization of perioperative chemotherapy for muscle-invasive bladder cancer. We also propose a framework to guide future knowledge translation activities in an effort to improve the care and outcomes of patients with this disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Adjuvant chemotherapy (ACT) is known to improve survival in patients with early-stage non-small cell lung cancer. Herein, we describe chemotherapy regimens used, dose modifications, survival, and treatment-related toxicity in the general population., Methods: All cases of non-small cell lung cancer diagnosed in Ontario in the period 2004-2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry in this population-based retrospective cohort study. We linked electronic records of treatment to the registry to identify all cases treated with ACT (n = 1032) and describe drugs, regimens, and dosages delivered. As a proxy measure of ACT-related toxicity, we evaluated deaths and hospitalizations within 16 weeks of starting ACT. Factors associated with dose modification were evaluated by logistic regression. The Cox proportional hazards model was used to describe associations between patient-, disease-, and treatment-related factors and survival., Results: ACT regimens were identified for 584 of 1032 ACT cases. Almost all cases included cisplatin- or carboplatin-based regimens (478/584, 82%, and 99/584, 17%, respectively). The most common regimen was a vinroelbine/cisplatin doublet (412/584, 71%); 64% of these cases had a dose reduction or omission. Dose modification was not associated with inferior survival on multivariate analysis. Twelve percent of all ACT cases were admitted to hospital within 16 weeks of starting ACT, and there was a 1.6% death rate potentially attributable to ACT. Survival of all ACT cases was comparable with outcomes reported in clinical trials., Conclusions: ACT regimens used, toxicity, and survival outcomes in the general population are comparable with those reported in clinical trials. Dose modifications used in clinical practice are not associated with inferior survival.

Context: Adjuvant chemotherapy (AC) improves survival among patients with resected colorectal cancer. However, the optimal timing from surgery to initiation of AC is unknown., Objective: To determine the relationship between time to AC and survival outcomes via a systematic review and meta-analysis. data sources: MEDLINE (1975 through January 2011), EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched to identify studies that described the relationship between time to AC and survival., Study Selection: Studies were only included if the relevant prognostic factors were adequately described and either comparative groups were balanced or results adjusted for these prognostic factors., Data Extraction: Hazard ratios (HRs) for overall survival and disease-free survival from each study were converted to a regression coefficient (β) and standard error corresponding to a continuous representation per 4 weeks of time to AC. The adjusted β from individual studies were combined using a fixed-effects model. Inverse variance (1/SE(2)) was used to weight individual studies. Publication bias was investigated using the trim and fill approach., Results: We identified 10 eligible studies involving 15,410 patients (7 published articles, 3 abstracts). Nine of the studies were cohort or population based and 1 was a secondary analysis from a randomized trial of chemotherapy. Six studies reported time to AC as a binary variable and 4 as 3 or more categories. Meta-analysis demonstrated that a 4-week increase in time to AC was associated with a significant decrease in both overall survival (HR, 1.14; 95% confidence interval [CI], 1.10-1.17) and disease-free survival (HR, 1.14; 95% CI, 1.10-1.18). There was no significant heterogeneity among included studies. Results remained significant after adjustment for potential publication bias and when the analysis was repeated to exclude studies of largest weight., Conclusion: In a meta-analysis of the available literature on time to AC, longer time to AC was associated with worse survival among patients with resected colorectal cancer.

The Ontario Cancer Registry (OCR) and the Surveillance, Epidemiology and End Results (SEER) databases were used to describe temporal trends in the incidence and survival of squamous cancers of the upper aerodigestive tract (UADT) in Ontario and the US between 1984 and 2001. Between the 1984-86 and 1999-01 periods, the age-adjusted incidence rate of all first primary cancers of the UADT decreased from 11.6 (11.2-12.0) to 8.8 (8.5-9.1) in Ontario and 13.0 (12.7-13.3) to 10.2 (10.0-10.4) in the US. Significant decreases in incidence were observed in many UADT sites but there was no significant change in the incidence of cancer of the oropharynx in either the US or Canada. Over the same period, the 5-year relative survival for all UADT cancers increased from 49.2% (47.2-51.2%) to 57.1%(55.0-59.1%) in Ontario and from 48.1% (46.9-49.3%) to 52.4% (51.2-53.6%) in the US. This significant improvement in the outcome of UADT cancer was largely due to a dramatic increase in the 5-year relative survival for cancers of the oropharynx from 31.1% (27.1-35.1%) to 53.6% (49.3-57.9%) in Ontario and from 35.3% (32.9-37.8%) to 51.0% (48.7-53.3%) in the US. Smaller increases in survival were observed in cancers of the oral cavity, nasopharynx, and hypopharynx, but there was no evidence of any increase in survival for cancer of the larynx. These results are consistent with the hypothesis that there has been a major change in the etiology of cancer of the oropharynx in Canada and the US and a concomitant change in its response to therapy., ((c) 2009 UICC.)

Extensive research has been carried out to establish the appropriate proportion of cancer patients requiring radiotherapy at some point during their illness. However, it is difficult to compare the actual rates against the appropriate rate, because calculating the actual rates requires life-long follow up of cancer patients. We have developed a method, referred to as the Multicohort Current Utilization Table (MCUT) method, to estimate the predicted lifetime utilization rates based on current medical practice. We implemented the method in SAS as a macro, and validated it by comparing the predicted and the actual utilization rates of radiotherapy in lung, breast, and prostate cancer cases diagnosed in Ontario, Canada. The MCUT method could be used to predict lifetime utilization rate of any medical services.

Background: Comorbidity is important to consider in clinical research on curative prostate carcinoma because of the role of competing risks. Five chart-based comorbidity indices were assessed for their ability to predict survival., Methods: This was a case-cohort study of prostate carcinoma patient cohort treated with curative intent in Toronto and Southeast Cancer Care Ontario regions between 1990 and 1996; the subcohort was drawn from these men, whereas cases were cohort members who died from causes other than prostate carcinoma. Comorbidity data were obtained from medical charts (269 subjects). Vital status, age, area of residence, and socioeconomic status information were available. Predictive validity was quantified by the percent variance explained (PVE) over and above age using proportional hazards modeling., Results: The Chronic Disease Score (CDS) (PVE = 11.3%; 95% confidence interval [95% CI], 3.5-22.8%), Index of Coexistent Disease (ICED) (PVE = 9.0%; 95% CI, 2.9-17.9%), Cumulative Illness Rating Scale (CIRS) (PVE = 7.2%; 95% CI, 1.4-17.1%), Kaplan-Feinstein Index (PVE = 4.9%; 95% CI, 0.6-12.8%), and Charlson Index (PVE = 3.8%; 95% CI, 0.3-10.9%) each explained some outcome variability beyond age. PVE differences among indices were not statistically significant. A comorbidity identified at the time of cancer diagnosis was the cause of death in 59.2% of cases (75% for cardiac or vascular causes)., Conclusions: The better-performing, more comprehensive indices (CDS, ICED, and CIRS) would be useful in measuring and controlling for comorbidity in this setting. The CDS was easiest to apply and explained the most outcome variability., (2006 American Cancer Society)

Introduction and Objective: Despite the high incidence of prostate cancer in Canada, there is currently limited information describing how these patients are being managed. The aim of this study was to review the surgical waiting times for radical prostatectomy in Ontario, utilizing existing population-based cancer databases, and to describe factors associated with prolonged waiting times., Methods: This is a retrospective, population-based, observational study of men diagnosed with prostate cancer in Ontario between 1980 and 2000. The sources of data include the Ontario Cancer Registry linked to hospital discharge data, as well as census data from Statistics Canada. Study variables include age, county of residence, teaching hospital status, hospital surgical volume, area-level median household income and cause-specific survival. Waiting times were compared across study variables using univariate and graphical methods. Survival was compared across geographic regions with differing average wait times., Results: We identified 9524 men treated with radical prostatectomy in Ontario over the study period and found the percentage of all patients with the disease who were treated surgically increasing from 3% to 20% over the last 2 decades. The overall time to prostatectomy has almost doubled with a median waiting time of 55 days in earlier eras to 91 days in 1996-2000. A few counties had significantly different wait times, whereas age and socio-economic factors were not associated with wait times across most eras. In the most recent eras, acute care hospitals and hospitals with higher surgical volumes had significantly higher waiting times (up to 20 days longer in 1996-2000, p<0.0001). Patients living in regions with the shortest wait times had statistically significant worse survival (p=0.02), implying that triaging has a greater impact than the potential effect of prolonged waits., Conclusions: The observed increases in waiting times for radical prostatectomy from this study are similar to the known increases in waiting times for radiotherapy. This increased time to treatment is an illustration of the stress on the health care system in Ontario.

Purpose: We compared the management and outcome of supraglottic cancer in Ontario, Canada, with that in the Surveillance, Epidemiology, and End Results (SEER) Program areas in the United States., Methods: Electronic, clinical, and hospital data were linked to cancer registry data and supplemented by chart review where necessary. Stage-stratified analyses compared initial treatment and survival in the SEER areas (n = 1,643) with a random sample from Ontario (n = 265). We also compared laryngectomy rates at 3 years in those patients 65 years and older at diagnosis., Results: Radical surgery was more commonly used in SEER, with absolute differences increasing with increasing stage: I/II, 17%; III, 36%; and IV, 45%. The 5-year survival rates were 74% in Ontario and 56% in SEER for stage I/II disease (P =.01), 55.7% in Ontario and 46.8% in SEER for stage III disease (P =.40), and 28.5% in Ontario and 29.1% in SEER for stage IV disease (P =.28). Cancer-specific survival results mirrored the overall survival results with the exception of stage IV disease, for which 34.6% of Ontario patients survived their cancer compared with 38.1% in SEER (P =.10). This stage IV difference was more pronounced when we further controlled for possible cause of death errors by restricting the comparison to patients with a single primary cancer (P =.01). Three-year actuarial laryngectomy rates differed. In stage I/II, these rates were 3% in Ontario compared with 35% in SEER (P < 10(-3)). In stage III disease, the rates were 30% and 54%, respectively (P =.03), and in stage IV disease they were 33% and 64% (P =.002)., Conclusion: There are large differences in the management of supraglottic cancer between the SEER areas of the United States and Ontario. Long-term larynx retention was higher in Ontario, where radiotherapy is widely regarded as the treatment of choice and surgery is reserved for salvage. In stages I to III, survival was similar in the two regions despite the differences in treatment policy. In stage IV, there may be a small survival advantage in the U.S. SEER areas related to the higher use of primary surgery.

Purpose: The objective of this study was to synthesize what is known about the relationship between delay in radiotherapy (RT) and the outcomes of RT., Methods: A systematic review of the world literature was conducted to identify studies that described the association between delay in RT and the probability of local control, metastasis, and/or survival. Studies were classified by clinical and methodologic criteria and their results were combined using a random-effects model., Results: A total of 46 relevant studies involving 15,782 patients met our minimum methodologic criteria of validity; most (42) were retrospective observational studies. Thirty-nine studies described rates of local recurrence, 21 studies described rates of distant metastasis, and 19 studies described survival. The relationship between delay and the outcomes of RT had been studied in diverse situations, but most frequently in breast cancer (21 studies) and head and neck cancer (12 studies). Combined analysis showed that the 5-year local recurrence rate (LRR) was significantly higher in patients treated with adjuvant RT for breast cancer more than 8 weeks after surgery than in those treated within 8 weeks of surgery (odds ratio [OR] = 1.62, 95% confidence interval [CI], 1.21 to 2.16). Combined analysis also showed that the LRR was significantly higher among patients who received postoperative RT for head and neck cancer more than 6 weeks after surgery than among those treated within 6 weeks of surgery (OR = 2.89; 95% CI, 1.60 to 5.21). There was little evidence about the impact of delay in RT on the risk of metastases or the probability of long-term survival in any situation., Conclusion: Delay in the initiation of RT is associated with an increase [corrected] in LRR in breast cancer and head and neck cancer. Delays in starting RT should be as short as reasonably achievable.