Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Validation of the Prognostic Utility of ESTRO/EORTC Oligometastatic Disease Classification: A Secondary Analysis From the Population-Based Phase II SABR-5 Trial.

PURPOSE: The recently developed European Society for Radiotherapy and Oncology (ESTRO)/European Organization for Research and Treatment of Cancer (EORTC) oligometastatic disease (OMD) classification has not been validated in terms of its prognostic significance. This study stratified patients from the phase II SABR-5 trial based on ESTRO/EORTC criteria and compared progression-free survival (PFS) and overall survival (OS) to determine the prognostic significance of the classification scheme. METHODS AND MATERIALS: The SABR-5 trial was a single arm phase II study conducted at the 6 regional cancer centers across British Columbia (BC), Canada, where SABR for oligometastases was only offered on trial. Patients with up to 5 oligometastases (total or not controlled by prior treatment and including induced OMD) underwent SABR to all lesions. Patients were 18 years of age or older, Eastern Cooperative Oncology Group 0 to 2, and life expectancy ≥6 months. PFS and OS were calculated using the Kaplan-Meier method and differences between OMD groups were assessed with log-rank tests. Univariable and multivariable analyses were performed using Cox regression modeling. RESULTS: Between November 2016 and July 2020, 381 patients underwent SABR on trial. Median follow-up was 27 months (interquartile range, 18-36). The most frequent OMD group was de novo OMD (69%), followed by repeat (16%) and induced (13%). OMD groups differed significantly in PFS (P < .001) but not OS (P = .069). The OMD classification was an independent predictor of both PFS (P = .005) and OS (P = .002). Of the 5 classification factors, only chronicity (synchronous, hazard ratio, 0.52; P = .027) and oligoprogression (hazard ratio, 2.05; P = .004) were independently prognostic for OS. CONCLUSIONS: In this large prospective cohort, the ESTRO/EORTC classification was an independent predictor of PFS and OS and should be used to identify specific patient groups for clinical trials. In this trial population, the prognostic power is largely attributable to chronicity and oligoprogression. Simplification of the framework may be possible in the future and allow for greater ease of use; however, further data on underrepresented OMD groups and histologies will be required.

Presenting stage and risk group in men dying of prostate cancer.

Introduction: Prostate cancer remains the 3rd leading cause of cancer-related mortality in Canadian men, and yet screening for prostate cancer continues to be controversial because the majority of men diagnosed with prostate cancer do not die of the disease. It also remains uncertain whether treatment of cases that can be treated with curative intent alters the mortality rate. There are very few studies describing the presenting stage, risk groups, and survival after diagnosis for men dying of prostate cancer in the literature. In this study, we explored these characteristics for all men who died of prostate cancer in British Columbia between 2013 and 2015. Methods: The population-based BC Cancer databases were used to identify all patients diagnosed between January 2013 and December 2015 who died of prostate cancer. Patient, tumour, and treatment characteristics were collected, and the risk grouping for each tumour was determined. The proportion of cases in each risk group at the time of diagnosis was determined. Survival time from diagnosis to death was calculated for all patients and for each risk group using the Kaplan-Meier method. Results: A total of 1256 patients died of prostate cancer. Of patients who presented with metastatic disease, 57.2% presented with a Gleason score of 8 or more, compared with only 35.7% of patients who presented with nonmetastatic disease (p < 0.0001). The presenting stage and risk group of those dying of prostate cancer were as follows: 32% metastatic disease, 3% regional (defined as node-positive), 39% localized high risk, 9% localized intermediate risk, 4% localized low risk, 6% localized not otherwise specified, and 7% unknown. Therefore, 80.3% of those with a known risk group presented with either localized high-risk, regional, or metastatic disease at diagnosis. The median survival times from diagnosis to death were 12 years for localized low-risk, 10 years for localized intermediate-risk, 6.5 years for localized high-risk, 4 years for regional, and 1.7 years for metastatic disease at diagnosis. Conclusions: This population-based analysis demonstrates that patients with localized high-risk, regional, or metastatic disease at diagnosis constitute the overwhelming majority of patients who die of prostate cancer in British Columbia. Unless these disease states can reliably be identified at an earlier low- or intermediate-risk localized state in the future, it is unlikely that treatment of localized low- and intermediate-risk cancer will have an impact on survival. Furthermore, patients with de novo metastatic disease had identifiable risk factors of a higher prostate-specific antigen and Gleason score. Further studies are required to confirm these results.

In the Era After the European Organisation for Research and Treatment of Cancer 'Boost' Study, is the Additional Radiotherapy to the Breast Tumour Bed Still Beneficial for Young Women?

AIMS: The European Organisation for Research and Treatment of Cancer (EORTC) 22,881-10,882 trial showed significant benefit of a radiotherapy boost (RTB) in women ≤40 years in a pre-hormone therapy (HT) era. We determined how the use of HT and RTB changed in response to clinical guidelines and whether the benefit of routine RTB was still observed in the HT era. MATERIALS AND METHODS: Between 1996 and 2004, a provincial database identified all women ≤40 years with breast cancer who met the inclusion criteria of the EORTC trial. In total, 411 patients were classified into three eras defined by the guidelines: era 1 (discretionary HT, discretionary RTB); era 2 (routine HT, discretionary RTB); era 3 (routine HT, routine RTB). HT use, RTB use and cumulative incidence of local recurrence were calculated and compared across eras. RESULTS: HT use increased after the first policy change from 13% to 75% for oestrogen receptor-positive patients (P < 0.01). RTB use also increased from 33% to 76% following the second policy change (P < 0.01). At 10 years, the cumulative incidence of local recurrence was 12% in era 1, 6% in era 2 and 6% in era 3 (era 2 versus era 3, P = 0.92). For patients in the routine HT era (eras 2 and 3 combined) there was no significant difference in local recurrence between RTB and 'no RTB' patients (6% versus 7%, P = 0.81). CONCLUSIONS: The routine use of HT and RTB increased significantly after new practice guidelines. Introduction of the HT guideline was associated with a 6% improvement in local recurrence at 10 years. No improvement in local recurrence was associated with the introduction of the RTB guideline in the HT era. The routine use of a boost in unselected young women with negative margins should be re-evaluated in the current HT era.

Pathologically Node-Positive Prostate Carcinoma - Prevalence, Pattern of Care and Outcome From a Population-Based Study.

AIMS: To evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database. PATIENTS AND METHODS: Patients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005-2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005-2007 and 139/2542 from 2010-2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan-Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010-2014). RESULTS: The median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5-108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7-11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32-10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58-9.46, P = 0.003). CONCLUSION: This study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca.

Impact of the Spinal Instability Neoplastic Score on Surgical Referral Patterns and Outcomes.

BACKGROUND: The Spinal Instability Neoplastic Score (sins) was developed to identify patients with spinal metastases who may benefit from surgical consultation. We aimed to assess the distribution of sins in a population-based cohort of patients undergoing palliative spine radiotherapy (rt) and referral rates to spinal surgery pre-rt. Secondary outcomes included referral to a spine surgeon post-rt, overall survival, maintenance of ambulation, need for re-intervention, and presence of spinal adverse events. METHODS: We retrospectively reviewed ct simulation scans and charts of consecutive patients receiving palliative spine rt between 2012 and 2013. Data were analyzed using Student's t-test, Chi-squared, Fisher's exact, and Kaplan-Meier log-rank tests. Patients were stratified into low (<7) and high (≥7) sins groups. RESULTS: We included 195 patients with a follow-up of 6.1 months. The median sins was 7. The score was 0 to 6 (low, no referral recommended), 7 to 12 (intermediate, consider referral), and 13 to 18 (high, referral suggested) in 34%, 59%, and 7% of patients, respectively. Eleven patients had pre-rt referral to spine surgery, with a surgery performed in 0 of 1 patient with sins 0 to 6, 1 of 7 with sins 7 to 12, and 1 of 3 with sins 13 to 18. Seven patients were referred to a surgeon post-rt with salvage surgery performed in two of those patients. Primary and secondary outcomes did not differ between low and high sins groups. CONCLUSION: Higher sins was associated with pre-rt referral to a spine surgeon, but most patients with high sins were not referred. Higher sins was not associated with shorter survival or worse outcome following rt.

Neoadjuvant systemic therapy in breast cancer: use and trends in radiotherapy practice.

BACKGROUND: The use of neoadjuvant systemic therapy (nast) in the treatment of breast cancer is increasing, and the role of adjuvant radiation therapy (rt) in that setting is uncertain. We sought to review and report the use of nast, its trends over time, and its relationship with the prescribing patterns of locoregional rt in a provincial cancer system. METHODS: Patients with stages i-iii breast cancer diagnosed during 2007-2012 were identified using a provincial database. Patient, tumour, and treatment characteristics were extracted. Multivariable logistic regression analyses were used to assess associations with the use of nast. Kaplan-Meier and Cox regression were used for survival analyses. RESULTS: Of the 11,658 patients who met the inclusion criteria, 602 (5%) had received nast. Use of nast was more frequent in stage iii patients (53%) than in stages i and ii patients (2%). In clinically lymph-node positive patients, a pathology assessment was made approximately 50% of the time. Higher clinical tumour stage and increasing clinical nodal stage predicted for increasing use of nast and of nodal rt after nast, but pathologic nodal status after nast was not associated with use of nodal rt. A statistically significant survival difference was observed between patients in the nast and no-nast groups, but that significance disappeared in a multivariable Cox regression analysis. CONCLUSIONS: This population-based study demonstrated 5% use of nast for breast cancer. Most patients received nodal rt after nast, and nodal rt was not associated with pathologic stage after nast. Findings likely reflect the realities of clinical practice and show that reliance on clinical nodal staging results in outcomes similar to those reported in the literature.

The Relationship between Hot Flashes and Testosterone Recovery after 12 Months of Androgen Suppression for Men with Localised Prostate Cancer in the ASCENDE-RT Trial.

AIMS: This study describes the proportion of men who experienced hot flashes (flashes), and the testosterone level at onset, peak frequency and cessation of flashes after 12 months of androgen deprivation therapy (ADT) in men undergoing curative-intent external beam radiation therapy (± brachytherapy boost). We also aimed to characterise testosterone recovery in this population. MATERIALS AND METHODS: This was a pre-specified secondary analysis of the ASCENDE-RT clinical trial. Three hundred and ninety-eight men were randomised. All received 12 months of ADT. The presence and frequency of flashes were patient reported. Cessation of flashes was defined as the first date a patient reported resolution of this symptom. Testosterone recovery was defined as any single serum testosterone above the threshold of 5, 7.5 or 10 nmol/l. RESULTS: The median age and follow-up were 68 years and 6.1 years. Flashes were reported in 93% of men. Flashes began and reached peak frequency at a median time of 4.0 months from the first luteinizing hormone-releasing hormone injection when testosterone levels had fallen to castrate. The median time to cessation of flashes was 7.6 months after the cessation of ADT (last injection + 3 months), when the median testosterone had risen to 5.7 nmol/l. A resolution of flashes was reported in 99% of patients. Baseline testosterone was available in 338 patients (85%). The median baseline testosterone was 13.2 nmol/l. The median (95% confidence interval) time of testosterone recovery to thresholds of 5 nmol/l, 7.5 nmol/l and 10 nmol/l were 9 (9-10) months, 13 (10-15) months and 18 (17-19) months from the cessation of ADT. At the time of censor, 96, 94 and 91% of patients had recovered testosterone to thresholds of 5, 7.5 and 10 nmol/l. CONCLUSION: Flashes occur at castrate levels of testosterone, with cessation of hot flashes antedating full recovery of testosterone in most patients. Rates of testosterone recovery after 12 months of ADT exceed 90%, although it can be delayed.

Using proliferative markers and Oncotype DX in therapeutic decision-making for breast cancer: the B.C. experience.

BACKGROUND: Proliferative scoring of breast tumours can guide treatment recommendations, particularly for estrogen receptor (er)-positive, her2-negative, T1-2, N0 disease. Our objectives were to □ estimate the proportion of such patients for whom proliferative indices [mitotic count (mc), Ki-67 immunostain, and Oncotype dx (Genomic Health, Redwood City, CA, U.S.A.) recurrence score (rs)] were obtained.□ compare the indices preferred by oncologists with the indices available to them.□ correlate Nottingham grade (ng) and its subcomponents with Oncotype dx.□ assess interobserver variation. METHODS: All of the er-positive, her2-negative, T1-2, N0 breast cancers diagnosed from 2007 to 2011 (n = 5110) were linked to a dataset of all provincial breast cancers with a rs. A 5% random sample of the 5110 cancers was reviewed to estimate the proportion that had a mc, Ki-67 index, and rs. Correlation coefficients were calculated for the rs with ng subcomponent scores. Interobserver variation in histologic grading between outside and central review pathology reports was assessed using a weighted kappa test. RESULTS: During 2007-2011, most cancers were histologically graded and assigned a mc; few had a Ki-67 index or rs. The ng and mc were significantly positively correlated with rs. The level of agreement in histologic scoring between outside and central pathology reports was good or very good. Very few cases with a low mc had a high rs (1.8%). CONCLUSIONS: Patients with low ng and mc scores are unlikely to have a high rs, and thus are less likely to benefit from chemotherapy. In the context of limited resources, that finding can guide clinicians about when a rs adds the most value.

Population-based analysis of the impact and generalizability of the NSABP-B24 study on endocrine therapy for patients with ductal carcinoma in situ of the breast.

BACKGROUND: In 1999, the National Surgical Adjuvant Breast and Bowel Project (NSABP)-B24 trial demonstrated that tamoxifen reduced relapse risk in women with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery (BCS) and radiotherapy (RT). In 2002, Allred's subgroup analysis showed that tamoxifen mainly benefitted estrogen receptor (ER)-positive disease. This study evaluates the impact and generalizability of these trial findings at the population level. PATIENTS AND METHODS: From 1989 to 2009, 2061 women with DCIS underwent BCS + RT in British Columbia. The following cohorts were analyzed: (1) pre-NSABP-B24 era (1989-1998, N = 417); (2) post-NSABP-B24 era (2000-2009, N = 1548). Cohort 2 was further divided into pre- and post-Allred eras. RESULTS: Endocrine therapy (ET) was used in 404/2061 (20%) patients. Median age of patients treated with compared with without ET, was 53 versus 57 years, (P < 0.0005). One of 417 (0.2%) versus 399/1548 (26%) patients took ET before versus after NSABP-B24. Among the post-Allred era cohort treated with ET (N = 227), tumors were ER-positive in 65%, ER-negative in 1%, and ER-unknown in 33%; whereas of those treated without ET (N = 801), ER was positive in 43%, negative in 15%, and unknown in 42% (P < 0.0005). On multivariable analysis of the post-NSABP-B24 era, ET was associated with improved event-free survival (EFS) (hazard ratio 0.6; P = 0.02); 5-year EFS were 96.9% with ET versus 94.5% without ET. CONCLUSIONS: ET use in DCIS patients treated with BCS + RT increased significantly after the NSABP-B24 study. ER+ disease and younger age were associated with increased ET use. ET was associated with improved EFS, confirming the generalizability of trial data at a population level.

Comparison of recurrence and survival rates after breast-conserving therapy and mastectomy in young women with breast cancer.

Multiple randomized trials have demonstrated that breast-conserving therapy with partial mastectomy and radiotherapy provides survival equivalent to that seen with mastectomy for patients with early-stage breast cancer. Breast-conserving therapy has been associated with better quality of life relative to mastectomy and has become the standard of care for patients with early-stage breast cancer. Young age has been identified as a risk factor for recurrence and death from breast cancer. Some studies have suggested that young women (less than 35 or 40 years of age) have inferior outcomes with breast-conserving therapy, implying that such women may be better served by mastectomy. On review of the available literature, there is no definitive evidence that mastectomy provides a consistent, unequivocal recurrence-free or overall survival benefit over breast-conserving therapy. However, available meta-analyses have not compared outcomes in young women specifically, and such analyses should be performed. In the interim, breast-conserving therapy is not contraindicated in young women (less than 40 years of age) and can be used cautiously; however, such women should be advised of the lack of unequivocal data proving that survival is equivalent to that with mastectomy in their age group.

A comparison of surgical and radiotherapy breast cancer therapy utilization in Canada (British Columbia), Scotland (Dundee), and Australia (Western Australia) with models of "optimal" therapy.

BACKGROUND: Different jurisdictions report different breast cancer treatment rates. Evidence-based utilization models may be specific to derived populations. We compared predicted optimal with actual radiotherapy utilization in British Columbia, Canada; Dundee, Scotland; and Perth, Western Australia. DESIGN: Data were analyzed for differences in demography, tumor, and treatment. Epidemiological data were fitted to published Australian optimal radiotherapy utilization trees and region-specific optimal treatment rates were calculated. Optimal and actual surgery/radiotherapy rates from 2 population-based and 1 institution-based registries were compared for patients diagnosed with breast cancer between 2000 and 2004, and 2002 for British Columbia. RESULTS: Mastectomy rates differed between British Columbia (40%), Western Australia (44%), and Dundee (47%, p<0.01). Radiotherapy rates differed between British Columbia (60%), Western Australia (52%), and Dundee (49%, p<0.01). Actual radiotherapy utilization rates were lower than optimal estimates. Region-specific optimal utilization rates at diagnosis varied from 57% to 71% for radiotherapy and 62% to 64% when taking into account patient preference. Variation was attributed to local differences in demography and tumor stage. CONCLUSIONS: Actual treatment rates varied, and were associated with patterns of care and guideline differences. Actual radiotherapy rates were lower than optimal rates. Differences between optimal and actual utilization may be due to access shortfalls, and patient preference.

Tumor markers in metastatic breast cancer subtypes: frequency of elevation and correlation with outcome.

BACKGROUND: Little is known about the correlations between tumor markers (TMs), breast cancer subtypes, site(s) of metastasis and prognosis. METHODS: Women diagnosed with metastatic breast cancer were included. Breast cancer subtypes were defined as LuminalA, LuminalB, LuminalHer2, Her2, Basal and non-Basal triple negative (TN). Levels of elevation of TM values [cancer antigen 15-3 (CA 15-3), carcinoembryonic antigen (CEA) and cancer antigen 125 (CA 125)] among the subtypes were analyzed. Site(s) of metastasis and outcomes were captured. RESULTS: Eight hundred and ten patients were included. Luminal subtypes were associated with an elevation in at least one TM: 90.8% of LuminalHer2+, 90% of LuminalB and 88.6% of LuminalA. TMs were less frequently elevated in Basal (74.1%) and non-Basal TN (71.4%) cases (P < 0.001). CA 15-3 was the most frequently elevated TM. The incidence of TM elevation did not differ between patients with solitary versus multiple metastatic sites. Breast cancer-specific survival (BCSS) was significantly worse for patients with elevated TMs (P = 0.001). CONCLUSIONS: TM elevation of CA 15-3, CEA and/or CA 125 was documented in the majority of patients with metastatic breast cancer with CA 15-3 occurring most commonly. Luminal subtypes expressed elevated TMs significantly more frequently compared with the non-Luminal groups. TM elevation was not different between the different sites of metastasis. Overall, elevated TMs predicted a worse BCSS.

Is breast-conserving therapy a safe option for patients with tumor multicentricity and multifocality?

BACKGROUND: We compared outcomes after breast-conserving therapy (BCT) and mastectomy in multicentric (MC)/multifocal (MF) versus unifocal breast cancer. PATIENTS AND METHODS: Women with stage I-II disease were classified as having unifocal or MC/MF disease. MC/MF and other prognostic factors were compared using binary logistic regression analysis. Univariate and multivariate analyses (MVAs) for relapse were carried out using cumulative incidence curves and Fine and Gray regression models. For the BCT group, matched analysis was added. RESULTS: Median follow-up was 7.9 years, 11 983 having BCT (unifocal: 11 683, MC/MF: 300) and 7771 having mastectomy (unifocal: 6884, MC/MF: 887). MC/MF patients treated with BCT were 50-69 years old, free of extensive ductal carcinoma in situ (DCIS), and had smaller tumors. The cumulative 10-year local recurrence rates among unifocal and MC/MF disease were 4.6% [95% confidence interval (CI) 4.1% to 5.0%] versus 5.5% (95% CI 2.6% to 9.9%) for the BCT group, P = 0.76 and 5.8% (95% CI 5.2% to 6.5%) versus 6.5% (95% CI 4.7% to 8.7%) for the mastectomy group, P = 0.77. MC/MF was not a significant factor for relapse or survival on MVA. In the matched analysis, relapse rates were similar in the unifocal and MC/MF groups, P = 0.60. CONCLUSION: BCT is a reasonable option in selected MC/MF cases, particularly those women aged 50-69 years old with small (<1 cm) MF tumors and without an extensive DCIS component.

Evolution in management of testicular seminoma: population-based outcomes with selective utilization of active therapies.

BACKGROUND: In this article, we report the evolution of treatment with increased use of active surveillance for stage I disease as well as risk-adapted chemotherapy for disseminated disease and associated outcomes of testicular seminoma in a contemporary population-based cohort. METHODS: All patients with histologically confirmed seminoma referred from 1999 to 2008 to the British Columbia Cancer Agency or Providence Cancer Center were retrospectively reviewed. Both institutions manage 90% of testicular cancers in their respective area. RESULTS: A total of 649 patients were included. Clinical stage (CS) distribution: CSI/II/III n=545/87/17. For CSI, there was a progressive and marked decrease in the utilization of prophylactic radiation (RT), and corresponding increase in the use of active surveillance. No deaths related to seminoma were reported in CSI patients. CSII or CSIII patients received RT or International Germ Cell Cancer Collaborative Group (IGCCCG) risk-appropriate chemotherapy with 101 of 104 patients being in long-term remission and 3 patients dying from treatment complications. For the entire seminoma population, <1% of patients died of seminoma or treatment after a median follow-up of 47 months (range 2-130 months). CONCLUSIONS: Progressive application of policies of active surveillance and earlier initiation of IGCCCG risk-adapted chemotherapy result in nearly universal control for all patients presenting with seminoma while reducing the burden of treatment.

Utilisation of radiotherapy in rural and urban areas in British Columbia compared with evidence-based estimates of radiotherapy needs for patients with breast, prostate and lung cancer.

AIMS: To compare the existing model estimates of the appropriate rates of radiotherapy for lung, breast and prostate cancers with actual radiotherapy rates in rural, semi-urban and urban areas, and in areas with short and long drive distances to cancer clinics in British Columbia. MATERIALS AND METHODS: All registered cases of lung, breast and prostate cancer diagnosed in British Columbia between 1997 and 2007 were identified. The proportion of cancers treated within 1 (RT1Y) and 5 years (RT5Y) of diagnosis were calculated according to rural, semi-urban and urban area, and areas associated with short and long drive distances to cancer clinics in British Columbia. RESULTS: RT1Y for lung, breast and prostate in urban and rural areas were 47/45%, 57/46% and 31/30%, and for short and long drive times were 47/44%, 56/50% and 31/31% compared with model estimates for initial radiotherapy needs of 41-45%, 57-61% and 32-37%, respectively. RT5Y for lung, breast and prostate in urban and rural areas were 52/47%, 59/48% and 42/39%, and for short and long drive times were 51/47%, 57/50% and 42/42% compared with model estimates for overall radiotherapy needs of 66-83%, 57-61% and 60-61%, respectively. CONCLUSIONS: Radiotherapy rates vary between and within urban and rural areas in British Columbia. Radiotherapy rates for breast and lung cancer patients are higher, and closer to model estimates of need, in urban areas and short drive time areas. Radiotherapy rates do not vary with drive time or rural versus urban classification for patients with prostate cancer.

General practitioner assessment of stage and performance status in lung cancer patients at a population level: implications for prognosis and radiotherapy needs analyses.

BACKGROUND: Stage, weight loss, and performance status (PS) are important prognostic factors and eligibility factors for curative intent therapy for lung cancer patients. Details of stage, weight loss, and PS are often not collected until referral to a cancer specialist, and since not all patients are referred to cancer specialists these important variables are not well defined at a population level. PATIENTS AND METHODS: Data on stage, weight loss, PS and referral pattern were requested from general practitioners (GPs) on all lung cancer patients diagnosed between May and June of 2002 in the province of British Columbia, Canada. Outcomes were analyzed in relation to survival and referral to a cancer centre. RESULTS: 395 patients were identified, and GP questionnaires were returned on 85% of the cases. Patients referred to a cancer centre shortly after diagnosis differed from those who were not referred. Patients who were not referred to a cancer centre consisted of two groups-patients with localized disease and good PS who tended to have a better survival than those who were referred, and patients with advanced disease and poor performance status who tended to have a worse survival than those who were referred. GP assessed stage and PS are prognostic factors for survival. CONCLUSIONS: GP assessed stage and PS are prognostic factors for survival in lung cancer patients. The case mix of patients who are not referred to a cancer centre shortly after their diagnosis differs from those that are referred.

A comparative analysis of radiotherapy use and patient outcome in males and females with breast cancer.

BACKGROUND: The aim was to determine whether gender was a significant prognostic factor for post-mastectomy relapse, after accounting for known prognostic factors and delivery of radiotherapy. PATIENTS AND METHODS: All patients diagnosed with invasive breast cancer between 1 January 1989 and 31 December 1998 who had undergone total mastectomy as primary therapy were identified from the British Columbia Cancer Agency's Breast Cancer Outcomes Unit database. Patients with pT4 or M1 disease were excluded. A comparison of patient, tumour and treatment factors was made between males and females. Outcomes were analysed in terms of locoregional-relapse free survival, breast cancer-specific survival and overall survival. RESULTS: Sixty males and 4181 females were identified. Multivariable analysis revealed increased tumour size, positive margin status, delivery of chemotherapy, positive nodal status and male gender to be significantly associated with the use of post-mastectomy radiotherapy. Multivariable analysis revealed tumour size, nodal status, tumour grade and presence of vascular space invasion to be significantly associated with locoregional recurrence. Gender was not a prognostic factor for locoregional recurrence, breast cancer-specific survival or overall survival on univariable or multivariable analysis. CONCLUSIONS: These data suggest that gender is not a prognostic factor in patients undergoing mastectomy for early stage breast cancer. Men having mastectomy for breast cancer should receive adjuvant radiotherapy following guidelines similar to those developed for females.

Comparison of 1- and 2-year screening intervals for women undergoing screening mammography.

We compared the long-term impact of 1- and 2-year screening mammography intervals using prognostic, screening, and outcome information for women aged 50-74 years obtained from the Screening Mammography Program of British Columbia in two time periods, prior to 1997 (policy of annual mammography) and after 1997 (biennial mammography). Survival was estimated for both periods using a prognostic model and the expected rate of interval and screen-detected cancers. The likelihood of a screen-detected cancer with annual screening was 2.32 per thousand screens and with biennial screening was 3.32 per thousand screens. The prognostic profile of screen-detected cancers was better than that of interval cancers. Among both screen-detected and interval cancers, the prognostic profiles with annual and biennial screening were similar. The estimated breast cancer-specific survival rates for women undergoing annual and biennial screening mammography were 95.2 and 94.6% at 5 years, and 90.4 and 89.2% at 10 years, respectively. Annual compared to biennial mammography was associated with a 1.2% increase in the estimated 10-year breast cancer-specific survival for women aged 50-74 years, diagnosed with invasive breast cancer after screening programme attendance.