Temporal trends in management and outcomes of testicular cancer: A population-based study.

BACKGROUND: Treatment guidelines for early-stage testicular cancer have increasingly recommended de-escalation of therapy with surveillance strategies. This study was designed to describe temporal trends in routine clinical practice and to determine whether de-escalation of therapy is associated with inferior survival in the general population. METHODS: The Ontario Cancer Registry was linked to electronic records of treatment to identify all patients diagnosed with testicular cancer treated with orchiectomy in Ontario during 2000-2010. Treatment after orchiectomy was classified as radiotherapy (RT), retroperitoneal lymph node dissection (RPLND), chemotherapy, or none. Surveillance was defined as no identified treatment within 90 days of orchiectomy. Overall survival (OS) and cancer-specific survival (CSS) were measured from the date of orchiectomy. RESULTS: The study population included 1564 and 1086 cases of seminomas and nonseminoma germ cell tumors (NSGCTs), respectively. Among patients with seminomas, there was a significant increase in the proportion of patients with no treatment within 90 days of orchiectomy (from 56% to 84%; P < .001); the use of RT decreased over time (from 38% to 8%; P < .001); and the use of chemotherapy remained stable (from 6% to 9%; P = .289). Practice patterns 90 days after orchiectomy remained stable over time among patients with NSGCTs: from 51% to 57% for no treatment (P = .435), from 43% to 43% for chemotherapy (P = .336), and from 9% to 3% for RPLND (P = .476). The OS rates for the entire cohort at 5 and 10 years were 97% and 96%, respectively; the CSS rates were 98% and 98%, respectively. There was no significant change in OS or CSS for patients with seminomas or NSGCTs during the study period. CONCLUSIONS: There has been substantial de-escalation in the treatment of testicular cancer in routine practice since 2000. Long-term survival in routine practice is excellent and has not decreased with the uptake of surveillance strategies. Cancer 2018;124:2724-2732. © 2018 American Cancer Society.

Utilization of pre-operative imaging for colon cancer: A population-based study.

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.

Simultaneous resection of primary colorectal cancer and synchronous liver metastases: a population-based study.

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.

CONTEXTE: La résection simultanée des cancers colorectaux primitifs et des métastases hépatiques synchrones suscitent de plus en plus d'intérêt. Nous décrivons la prise en charge et les résultats de patients de la population générale ayant subi une résection simultanée. MÉTHODES: Tous les patients atteints d'un cancer colorectal ayant bénéficié d'une résection chirurgicale des métastases hépatiques entre 2002 et 2009 ont été identifiés au moyen du Registre des cas de cancer de l'Ontario en population générale et des dossiers électroniques associés sur le traitement. La maladie synchrone a été définie comme le fait d'avoir subi une chirurgie de résection des métastases hépatiques du cancer colorectal dans les 12 semaines de la chirurgie de la tumeur primitive. RÉSULTATS: Pendant la période de l'étude, 1310 patients ont subi une résection des métastases hépatiques du cancer colorectal. Sur ce nombre, 226 (17 %) patients présentaient une maladie synchrone; 100 (44 %) patients ont subi une résection simultanée et 126 (56 %) patients ont subi une résection en 2 temps. Dans les groupes des résections simultanées et des résections en 2 temps, le nombre moyen de lésions hépatiques réséquées était de 1,6 et de 2,3, respectivement (p < 0,001); la taille moyenne de la lésion la plus importante était de 3,1 et de 4,8 cm, respectivement (p < 0,001) et le taux de résection hépatique majeure était de 21 % et de 79 %, respectivement (p < 0,001). La mortalité postopératoire après résection simultanée à 90 jours était inférieure à 5 %. La survie globale à 5 ans et la survie par cause des patients avec résection simultanée étaient de 36 % (intervalle de confiance [IC] de 95 %, 26 %-45 %) et de 37 % (IC 95 %, 25 %-50 %), respectivement. Les résections simultanées sont courantes au sein de la population générale. On commence à adopter une approche plus conservatrice pour les résections simultanées en limitant l'étendue de la résection hépatique. La mortalité postopératoire et la survie à long terme de cette population de patients sont semblables à celles signalées dans d'autres séries récentes. CONCLUSION: Comparativement à l'approche en 2 temps, les patients avec résections simultanées présentaient moins de métastases hépatiques et des métastases de plus petite taille, et les résections pratiquées étaient moins agressives. Le tiers de ces patients ont obtenu une survie à long terme.

The relationship between time to initiation of adjuvant chemotherapy and survival in breast cancer: a systematic review and meta-analysis.

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 (ß) 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.

Outcomes of Resected Colorectal Cancer Lung Metastases in Routine Clinical Practice: A Population-Based Study.

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.

Patterns of Referral for Adjuvant Chemotherapy for Stage II and III Colon Cancer: A Population-Based Study.

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.

Utilisation of preoperative imaging for muscle-invasive bladder cancer: a population-based study.

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.

Use of Palliative Chemotherapy for Advanced Bladder Cancer: Patterns of Care in Routine Clinical Practice.

BACKGROUND: Palliative chemotherapy for advanced bladder cancer is recommended in clinical practice guidelines. Patterns of care in routine clinical practice have not been well described. This article describes use rates of chemotherapy and referral rates to medical oncology in the last year of life among patients who have died of bladder cancer. METHODS: A population-based cohort of patients with bladder cancer was identified from the Ontario Cancer Registry; the study population included patients who died of bladder cancer between 1995 and 2009. Electronic records of treatment and physician billing records were used to identify treatment patterns and referral to medical oncology. Log-binomial and modified Poisson regression were used to examine factors associated with chemotherapy use and medical oncology consultation. RESULTS: A total of 8,005 patients died of bladder cancer, 25% (n=1,964) of whom received chemotherapy in the last year of life. Use was independently associated with patient age, comorbidities, socioeconomic status, sex, time period, and treatment region. A total of 68% (n=5,426) of patients were seen by a medical oncologist. Referral to medical oncology was associated with age, comorbidities, year of death. Geographic variation was seen with chemotherapy use-from 18% to 30%-that persisted on adjusted analysis. CONCLUSIONS: The efficacy of palliative chemotherapy demonstrated in clinical trials and recommended in guidelines has not translated into widespread use in practice. Understanding the extent to which patient preferences and health system factors influence use is needed. Access to acceptable palliative systemic treatments remains an unmet need for most patients dying of bladder cancer.

Use and Effectiveness of Adjuvant Chemotherapy for Stage III Colon Cancer: A Population-Based Study.

BACKGROUND: International guidelines recommend adjuvant chemotherapy (ACT) for patients with stage III colon cancer. Whether efficacy observed in clinical trials translates to effectiveness in routine practice is less well understood. Here we describe use and outcomes of ACT in routine practice. METHODS: All cases of colon cancer treated with surgery in Ontario 2002-2008 were identified using the population-based Ontario Cancer Registry. Linked electronic records of treatment identified surgery and ACT use. Pathology reports were obtained for a random 25% sample of all cases; patients with stage III disease were included in the study population. Modified Poisson regression was used to evaluate factors associated with ACT. Cox proportional hazards model and propensity score analysis were used to explore the association between ACT and cancer-specific survival (CSS) and overall survival (OS). RESULTS: The study population included 2,801 patients with stage III colon cancer; 66% (n=1,861) received ACT. ACT use rates varied substantially across age groups; 90% among patients aged 20 to 49 years versus 68% among those aged 70 to 79 years (P<.001). ACT use was inversely associated with comorbidity (P<.001) and socioeconomic status (P=.049). In adjusted analyses advanced age is associated with inferior CSS and OS. Use of ACT was associated with decreased risk of death from cancer (hazard ratio [HR], 0.63; 95% CI, 0.54-0.73) and decreased risk of death from any cause (HR, 0.63; 95% CI, 0.55-0.71). This result was consistent in the propensity score analysis. CONCLUSIONS: One-third of patients with stage III colon cancer in the general population do not receive ACT. Use of ACT in routine practice is associated with a substantial improvement in CSS and OS.

Pathological factors associated with survival benefit from adjuvant chemotherapy (ACT): a population-based study of bladder cancer.

OBJECTIVE: To evaluate whether pathological factors are associated with differential effect of adjuvant chemotherapy (ACT). PATIENTS AND METHODS: In this population-based retrospective cohort study, we linked electronic records of treatment and surgical pathology to the Ontario Cancer Registry. The study population included all patients with muscle-invasive bladder cancer undergoing cystectomy in Ontario 1994-2008. Factors associated with overall (OS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards. We tested for interaction between the following variables and ACT effect-size: N-stage, margin status, T-stage, and lymphovascular invasion (LVI). RESULTS: The study population included 2802 patients; 19% were treated with ACT. Interaction terms with ACT for OS/CSS are: N-stage (both P < 0.001); margin status (P = 0.054/P = 0.048); T-stage (P = 0.509/P = 0.286); and LVI (P = 0.361/P = 0.405). Magnitude of effect for ACT was greater for patients with node-positive disease [OS: hazard ratio (HR) 0.56, 95% confidence interval (CI) 0.47-0.67; CSS: HR 0.60, 95% CI 0.49-0.72] than for patients with node-negative disease (OS: HR 0.80, 95% CI 0.61-1.03; CSS: HR 0.79, 95% CI 0.59-1.07). ACT was also associated with greater effect among patients with involved margins (OS: HR 0.45, 95% CI 0.33-0.62; CSS: HR 0.40, 95% CI 0.28-0.57) compared with patients with negative margins (OS: HR 0.75, 95% CI 0.65-0.87; CSS: HR 0.79, 95% CI 0.67-0.93). CONCLUSIONS: In this population-based cohort study we observe evidence of interaction between ACT effect and nodal stage and surgical margin status. Our results suggest that patients at highest risk of disease recurrence may derive greatest benefit from ACT.

Reporting trends and prognostic significance of lymphovascular invasion in muscle-invasive urothelial carcinoma: a population-based study.

OBJECTIVES: To investigate reporting patterns and outcomes associated with lymphovascular invasion in a general population setting. METHODS: We identified all cystectomy patients with muscle-invasive urothelial cancer in Ontario, Canada, 1994-2008. Surgical pathology reports were analyzed for pathological variables including lymphovascular invasion. Lymphovascular invasion reporting patterns were described over time. A Cox proportional hazards model was used to evaluate the association of lymphovascular invasion with survival. RESULTS: Of the 2802 cases identified, lymphovascular invasion status was reported in 75%. Lymphovascular invasion reporting significantly improved over the study period and was correlated with poor prognostic pathological features (T stage and N stage). Comprehensive cancer center status was not consistently associated with lymphovascular invasion reporting. Patients with lymphovascular invasion had substantially lower survival than patients who were lymphovascular invasion-negative or whose lymphovascular invasion status was unstated (P < 0.001). Lymphovascular invasion was independently associated with survival in patients regardless of lymph node metastasis. After adjusting for age, stage, comorbidity, margin status and adjuvant chemotherapy, lymphovascular invasion remained strongly associated with reduced survival (hazard ratio 1.98, 95% confidence interval 1.71-2.29). CONCLUSIONS: Although routine reporting of lymphovascular invasion has improved over the years, pathologists appear to be biased towards evaluating lymphovascular invasion in patients with high-stage disease. Despite this bias, lymphovascular invasion remains an important prognostic factor among patients treated by cystectomy. Pathologists in general practice should report lymphovascular invasion status more consistently and urologists should hold their pathology colleagues to a higher standard.

Perioperative chemotherapy for muscle-invasive bladder cancer: A population-based outcomes study.

BACKGROUND: Practice guidelines recommend neoadjuvant chemotherapy (NACT) for bladder cancer. However, the evidence in support of adjuvant chemotherapy (ACT) is less robust. Here we describe whether the evidence of efficacy for NACT/ACT was sufficient to change clinical practice and whether the efficacy demonstrated in clinical trials was translated into effectiveness in the general population. METHODS: Electronic records of treatment were linked to the population-based Ontario Cancer Registry to identify all patients with bladder cancer treated with cystectomy in Ontario 1994-2008. Utilization of NACT/ACT was compared across 1994-1998, 1999-2003, and 2004-2008. Logistic regression was used to analyze factors associated with NACT/ACT. Cox model and propensity score analyses were used to explore the association between ACT and survival. RESULTS: Two thousand forty-four patients underwent cystectomy for muscle-invasive bladder cancer (MIBC). Use of NACT remained stable (mean, 4%), whereas utilization of ACT increased over time (16%, 18%, 22%; P = .001). Advanced stage (T3/T4; OR, 1.83; 95% CI, 1.38-2.46) and node-positive disease (OR, 8.10; 95% CI, 6.20-10.7) were associated with greater utilization of ACT. Five-year overall survival (OS) and cancer-specific survival (CSS) for all patients was 29% (95% CI, 28%-31%) and 33% (95% CI, 31%-35%), respectively. Utilization of ACT was associated with improved OS (HR, 0.71; 95% CI, 0.62-0.81) and CSS (HR, 0.73; 95% CI, 0.64-0.84). Results were consistent in propensity score analyses. CONCLUSIONS: NACT remains substantially underutilized in routine clinical practice. Our results suggest that perioperative chemotherapy is associated with a substantial survival benefit in the general population. Patients who are planning to undergo cystectomy for bladder cancer should be reviewed by a multidisciplinary team.

Time to adjuvant chemotherapy and survival in non-small cell lung cancer: a population-based study.

BACKGROUND: The time interval between surgery and initiation of adjuvant chemotherapy (ACT) may impact survival in colorectal and breast cancers. This is the first report describing the association between time to adjuvant chemotherapy (TTAC) and survival in non-small cell lung cancer (NSCLC). METHODS: All cases of NSCLC diagnosed in Ontario, Canada, from 2004 to 2006 who underwent surgical resection (n = 3354) were identified using the Ontario Cancer Registry. TTAC was defined as the interval between dates of surgery and initiation of ACT. Factors associated with TTAC greater than 10 weeks were evaluated by logistic regression. The Cox proportional hazards model was used to describe the effect of delayed TTAC (analyzed as a continuous variable) on overall survival. RESULTS: Among the 1032 cases treated with ACT, the median TTAC was 8 weeks (range, 1-16 weeks); 35% of cases initiated ACT more than 10 weeks after surgery. Rates of TTAC greater than 10 weeks varied widely across regions (11%-50%, P = .001). There was no significant association between increased comorbidity and delayed TTAC; there was a trend toward greater delay in TTAC with longer postoperative hospital stay (P = .054) and postoperative readmission to hospital (P = .056). Male sex, higher stage of disease, greater comorbidity, and more extensive surgery were independently associated with inferior survival. TTAC was not associated with overall survival (odds ratio = 1.00, 95% confidence interval = 0.99-1.00). CONCLUSIONS: One-third of NSCLC patients treated with ACT in the general population start ACT beyond 10 weeks after surgery. Delayed TTAC does not appear to be associated with inferior survival in NSCLC.

Assessing the impact of comorbid illnesses on death within 10 years in prostate cancer treatment candidates.

BACKGROUND: Treatment choice in prostate cancer is influenced by pre-existing comorbid illnesses, but information about their individual prognostic impact is sparse, and only 1 comorbidity index has been developed for this setting. The authors assessed the impact of individual comorbid illnesses on the risk of early, other-cause death in prostate cancer treatment candidates and propose a modification of an existing comorbidity scale. METHODS: A population-based case-cohort study included patients diagnosed from 1990 through 1998 in Ontario, Canada who had planned curative radiotherapy or prostatectomy. The subcohort numbered 1643, and the case sample (those dying of other causes within 10 years) numbered 630. Ontario Cancer Registry data were linked to data from medical charts, including: age, comorbidity using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G), stage, prostate-specific antigen, Gleason score, and treatment. Cox proportional hazards regression assessed the age-adjusted association between CIRS-G and other-cause death. RESULTS: Respiratory and cardiac diseases were the most common comorbidities and most strongly associated with an increased risk of death. Other important comorbidities included vascular disease, renal disease, and diabetes. The modified CIRS-G(pros) score yielded a relative risk (RR) of 1.64 (95% confidence interval [CI], 1.52-1.76) for those scoring 1 compared with 0 and RR 1.18 (95% CI, 1.15-1.21) for each increment above 1. Except for those aged >80 years, results were consistent across treatment type and age group. CONCLUSIONS: This study provides estimates of the role of individual comorbid illnesses in prostate cancer. The modified CIRS-G(pros) could be useful in the clinic and in future research on this patient population.

Association between time to initiation of adjuvant chemotherapy and survival in colorectal cancer: a systematic review and meta-analysis.

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 (ß) and standard error corresponding to a continuous representation per 4 weeks of time to AC. The adjusted ß 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.

Temporal trends in the incidence and survival of cancers of the upper aerodigestive tract in Ontario and the United States.

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.

Real-world data: towards achieving the achievable in cancer care.

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.

Use of radiotherapy for bladder cancer: A population-based study of evolving referral and practice patterns.

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.

Estimating the optimal perioperative chemotherapy utilization rate for muscle-invasive bladder cancer.

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%.