Clinical outcomes for men with positive surgical margins after radical prostatectomy-results from the South Australian Prostate Cancer Clinical Outcomes Collaborative community-based registry.

Objective: Positive surgical margins (PSMs) after radical prostatectomy (RP) indicate failure of surgery to completely clear cancer. PSMs confer an increased risk of biochemical recurrence (BCR), but how more robust outcomes are affected is unclear. This study investigated factors associated with PSMs following RP and determined their impact on clinical outcomes (BCR, second treatment [radiotherapy and/or androgen deprivation therapy], and prostate cancer-specific mortality [PCSM]). Methods: The study cohort included men diagnosed with prostate cancer (pT2-3b/N0/M0) between January 1998 and June 2016 who underwent RP from the South Australian Prostate Cancer Clinical Outcomes Collaborative database. Factors associated with risk of PSMs were identified using Poisson regression. The impact of PSMs on clinical outcomes (BCR, second treatment, and PCSM) was assessed using competing risk regression. Results: Of the 2827 eligible participants, 28% had PSMs-10% apical, 6% bladder neck, 17% posterolateral, and 5% at multiple locations. Median follow-up was 9.6 years with 81 deaths from prostate cancer recorded. Likelihood of PSM increased with higher pathological grade and pathological tumor stage, and greater tumour volume, but decreased with increasing surgeon volume (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.88-0.98, per 100 previous prostatectomies). PSMs were associated with increased risk of BCR (adjusted sub-distribution hazard ratio [sHR] 2.5; 95% CI 2.1-3.1) and second treatment (sHR 2.9; 95% CI 2.4-3.5). Risk of BCR was increased similarly for each PSM location, but was higher for multiple margin sites. We found no association between PSMs and PCSM. Conclusion: Our findings support previous research suggesting that PSMs are not independently associated with PCSM despite strong association with BCR. Reducing PSM rates remains an important objective, given the higher likelihood of secondary treatment with associated comorbidities.

Comparison of outcomes of different biopsy schedules among men on active surveillance for prostate cancer: An analysis of the G.A.P.3 global consortium database.

BACKGROUND: The optimal interval for repeat biopsy during active surveillance (AS) for prostate cancer is yet to be defined. This study examined whether risk of upgrading (to grade group ≥ 2) or risk of converting to treatment varied according to intensity of repeat biopsy using data from the GAP3 consortium's global AS database. MATERIALS AND METHODS: Intensity of surveillance biopsy schedules was categorized according to centers' protocols: (a) Prostate Cancer Research International Active Surveillance project (PRIAS) protocols with biopsies at years 1, 4, and 7 (10 centers; 7532 men); (b) biennial biopsies, that is, every other year (8 centers; 4365 men); and (c) annual biopsy schedules (4 centers; 1602 men). Multivariable Cox regression was used to compare outcomes according to biopsy intensity. RESULTS: Out of the 13,508 eligible participants, 56% were managed according to PRIAS protocols (biopsies at years 1, 4, and 7), 32% via biennial biopsy, and 12% via annual biopsy. After adjusting for baseline characteristics, risk of converting to treatment was greater for those on annual compared with PRIAS biopsy schedules (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.51-1.83; p < 0.001), while risk of upgrading did not differ (HR = 0.96; 95% CI = 0.84-1.10). CONCLUSION: Results suggest more frequent biopsy schedules may deter some men from continuing AS despite no evidence of grade progression.

Imaging Biomarkers as Predictors for Breast Cancer Death.

BACKGROUND: To differentiate the risk of breast cancer death in a longitudinal cohort using imaging biomarkers of tumor extent and biology, specifically, the mammographic appearance, basal phenotype, histologic tumor distribution, and conventional tumor attributes. METHODS: Using a prospective cohort study design, 498 invasive breast cancer patients diagnosed between 1996 and 1998 were used as the test cohort to assess the independent effects of the imaging biomarkers and other predictors on the risk of breast cancer death. External validation was performed with a cohort of 848 patients diagnosed between 2006 and 2010. RESULTS: Mammographic tumor appearance was an independent predictor of risk of breast cancer death (P=0.0003) when conventional tumor attributes and treatment modalities were controlled. The casting type calcifications and architectural distortion were associated with 3.13-fold and 3.19-fold risks of breast cancer death, respectively. The basal phenotype independently conferred a 2.68-fold risk compared with nonbasal phenotype. The observed deaths did not differ significantly from expected deaths in the validation cohort. The application of imaging biomarkers together with other predictors classified twelve categories of risk for breast cancer death. CONCLUSION: Combining imaging biomarkers such as the mammographic appearance of the tumor with the histopathologic distribution and basal phenotype, accurately predicted long-term risk of breast cancer death. The information may be relevant for determining the need for molecular testing, planning treatment, and determining the most appropriate clinical surveillance schedule for breast cancer patients.

Optimum Tools for Predicting Clinical Outcomes in Prostate Cancer Patients Undergoing Radical Prostatectomy: A Systematic Review of Prognostic Accuracy and Validity.

Prostate cancer is a heterogeneous disease whose therapies frequently have adverse effects. Informed patient counseling regarding likely clinical outcomes is therefore important. In this systematic review we aimed to identify all external validations of tools that are used to predict clinical outcomes in patients undergoing radical prostatectomy and evaluate which are optimum for clinical implementation. PubMed and EMBASE were searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, radical prostatectomy, and prognosis. Titles and abstracts were screened and relevant studies were advanced to full-text review. Reference lists were reviewed for further studies. The Centre for Evidence Based Medicine prognostic tool was used for critical appraisal. Seventy-three studies externally validated 13 pre- and 41 postoperative tools for the prediction of biochemical recurrence (BCR), aggressive BCR, metastasis, and prostate cancer-specific mortality (PCSM). Recommendations for clinical implementation were made on the basis of accuracy, cohort sizes, and consistency. The accuracy of recommended tools ranged from 68% to 79% and 72% to 92% among the largest validation cohorts for pre- and postoperative tools. For preoperative prognosis we recommended the Cancer of the Prostate Risk Assessment (CAPRA) and Stephenson nomograms for BCR, the CAPRA nomogram for aggressive BCR as well as metastasis, and the D'Amico criteria for PCSM. For postoperative prognosis we recommended the CAPRA-Surgery (CAPRA-S), Stephenson, Kattan, Duke prostate cancer (DPC), and the Suardi nomograms for the prediction of BCR, the DPC nomogram for aggressive BCR, the CAPRA-S and Eggener nomograms for metastasis, and the Eggener nomogram for PCSM. Use of these tools should help clinicians deliver accurate, evidence-based counseling to patients undergoing prostatectomy.

Tools for Predicting Clinical and Patient-reported Outcomes in Prostate Cancer Patients Undergoing Androgen Deprivation Therapy: A Systematic Review of Prognostic Accuracy and Validity.

Androgen deprivation therapy (ADT) can result in a range of adverse symptoms that reduce patients' quality of life. Careful patient counseling on the likely clinical outcomes and adverse effects is therefore vital. The present systematic review was undertaken to identify and characterize all the tools used for the prediction of clinical and patient-reported outcome measures (PROMs) in patients with prostate cancer undergoing ADT. PubMed and EMBASE were systematically searched from 2007 to 2016. Search terms related to the inclusion criteria were: prostate cancer, clinical outcomes, PROMs, ADT, and prognosis. Titles and abstracts were reviewed to find relevant studies, which were advanced to full-text review. The reference lists were screened for additional studies. The Centre for Evidence Based Medicine critical appraisal of prognostic studies tool was applied. The search strategy identified 8755 studies. Of the 8755 studies, 22 on clinical outcomes were identified. However, no studies of PROMs were found. Nine tools could be used to predict clinical outcomes in treatment-naive patients and 10 in patients with recurrence. The Japan Cancer of the Prostate Risk Assessment (J-CAPRA) nomogram was the best performing and validated tool for the prediction of clinical outcomes in treatment-naive patients, and the Chi and Shamash prognostic indexes have been validated for use in patients with castration-resistant disease in different clinical contexts. Using the J-CAPRA nomogram should help clinicians deliver accurate, evidence-based counseling to patients undergoing primary ADT. A strong need exists for primary studies that derive and validate tools for the prediction of PROMs in patients undergoing ADT under any circumstance because these are currently absent from the literature.

Prostate cancer outcomes for men who present with symptoms at diagnosis.

OBJECTIVE: To compare clinical features, treatments and outcomes in men with non-metastatic prostate cancer (PCa) according to whether they were referred for symptoms or elevated prostate-specific antigen (PSA) level. PATIENTS AND METHODS: This study used data from the South Australia Prostate Cancer Clinical Outcomes Collaborative database; a multi-institutional clinical registry covering both the public and private sectors. We included all non-metastatic cases from 1998 to 2013 referred for urinary/prostatic symptoms or elevated PSA level. Multivariate Poisson regression was used to identify characteristics associated with symptomatic presentation and compare treatments according to reason for referral. Outcomes (i.e. overall survival, PCa-specific survival, metastasis-free survival and disease-free survival) were compared using multivariate Cox proportional hazards and competing risk regression. RESULTS: Our analytical cohort consisted of 4 841 men with localized PCa. Symptomatic men had lower-risk disease (incidence ratio [IR] 0.70, 95% confidence interval [CI] 0.61-0.81 for high vs low risk), fewer radical prostatectomies (IR 0.64, CI: 0.56-0.75) and less radiotherapy (IR 0.86, CI: 0.77-0.96) than men presenting with elevated PSA level. All-cause mortality (hazard ratio [HR] 1.31, CI: 1.16-1.47), disease-specific mortality (HR 1.42, CI: 1.13-1.77) and risk of metastases (HR 1.36, CI: 1.13-1.64) were higher for men presenting with symptoms, after adjustment for other clinical characteristics; however, risk of disease progression did not differ (HR 0.90, CI: 0.74-1.07) amongst those treated curatively. Subgroup analyses indicated poorer PCa survival for symptomatic referral among men undergoing radical prostatectomy (HR 3.4, CI: 1.3-8.8), those aged >70 years (HR 1.4, CI: 1.0-1.8), men receiving private treatment (HR 2.1, CI: 1.3-3.3), those diagnosed via biopsy (HR 1.3, CI: 1.0-1.7) and those diagnosed before 2006 (HR 1.6, CI: 1.2-2.7). CONCLUSION: Our results suggest that symptomatic presentation may be an independent negative prognostic indicator for PCa survival. More complete assessment of disease grade and extent, more definitive treatment and increased post-treatment monitoring among symptomatic cases may improve outcomes. Further research to determine any pathophysiological basis for poor outcomes in symptomatic men is warranted.

Sociodemographic disparities in survival from colorectal cancer in South Australia: a population-wide data linkage study.

BACKGROUND: Inequalities in survival from colorectal cancer (CRC) across socioeconomic groups and by area of residence have been described in various health care settings. Few population-wide datasets which include clinical and treatment information are available in Australia to investigate disparities. This study examines socio-demographic differences in survival for CRC patients in South Australia (SA), using a population-wide database derived via linkage of administrative and surveillance datasets. METHODS: The study population comprised all cases of CRC diagnosed in 2003-2008 among SA residents aged 50-79 yrs in the SA Central Cancer Registry. Measures of socioeconomic status (area level), geographical remoteness, clinical characteristics, comorbid conditions, treatments and outcomes were derived through record linkage of central cancer registry, hospital-based clinical registries, hospital separations, and radiotherapy services data sources. Socio-demographic disparities in CRC survival were examined using competing risk regression analysis. RESULTS: Four thousand six hundred and forty one eligible cases were followed for an average of 4.7 yrs, during which time 1525 died from CRC and 416 died from other causes. Results of competing risk regression indicated higher risk of CRC death with higher grade (HR high v low =2.25, 95% CI 1.32-3.84), later stage (HR C v A = 7.74, 95% CI 5.75-10.4), severe comorbidity (HR severe v none =1.21, 95% CI 1.02-1.44) and receiving radiotherapy (HR = 1.41, 95% CI 1.18-1.68). Patients from the most socioeconomically advantaged areas had significantly better outcomes than those from the least advantaged areas (HR =0.75, 95% 0.62-0.91). Patients residing in remote locations had significantly worse outcomes than metropolitan residents, though this was only evident for stages A-C (HR = 1.35, 95 % CI 1.01-1.80). These disparities were not explained by differences in stage at diagnosis between socioeconomic groups or area of residence. Nor were they explained by differences in patient factors, other tumour characteristics, comorbidity, or treatment modalities. CONCLUSIONS: Socio-economic and regional disparities in survival following CRC are evident in SA, despite having a universal health care system. Of particular concern is the poorer survival for patients from remote areas with potentially curable CRC. Reasons for these disparities require further exploration to identify factors that can be addressed to improve outcomes.

A novel case-control design to estimate the extent of over-diagnosis of breast cancer due to organised population-based mammography screening.

Debate about the extent of breast cancer over-diagnosis due to mammography screening has continued for over a decade, without consensus. Estimates range from 0 to 54%, but many studies have been criticized for having flawed methodology. In this study we used a novel study design to estimate over-diagnosis due to organised mammography screening in South Australia (SA). To estimate breast cancer incidence at and following screening we used a population-based, age-matched case-control design involving 4,931 breast cancer cases and 22,914 controls to obtain OR for yearly time intervals since women's last screening mammogram. The level of over-diagnosis was estimated by comparing the cumulative breast cancer incidence with and without screening. The former was derived by applying ORs for each time window to incidence rates in the absence of screening, and the latter, by projecting pre-screening incidence rates. Sensitivity analyses were undertaken to assess potential biases. Over-diagnosis was estimated to be 8% (95%CI 2-14%) and 14% (95%CI 8-19%) among SA women aged 45 to 85 years from 2006-2010, for invasive breast cancer and all breast cancer respectively. These estimates were robust when applying various sensitivity analyses, except for adjustment for potential confounding assuming higher risk among screened than non-screened women, which reduced levels of over-diagnosis to 1% (95%CI 5-7%) and 8% (95%CI 2-14%) respectively when incidence rates for screening participants were adjusted by 10%. Our results indicate that the level of over-diagnosis due to mammography screening is modest and considerably lower than many previous estimates, including others for Australia.

Treatment patterns among colorectal cancer patients in South Australia: a demonstration of the utility of population-based data linkage.

RATIONALE, AIMS AND OBJECTIVES: Population level data on colorectal cancer (CRC) management in Australia are lacking. This study assessed broad level patterns of care and concordance with guidelines for CRC management at the population level using linked administrative data from both the private and public health sectors across South Australia. Disparities in CRC treatment were also explored. METHOD: Linking information from the South Australian Cancer Registry, hospital separations, radiotherapy services and hospital-based cancer registry systems provided data on the socio-demographic, clinical and treatment characteristics for 4641 CRC patients, aged 50-79 years, diagnosed from 2003 to 2008. Factors associated with receiving site/stage-specific treatments (surgery, chemotherapy and radiotherapy) and overall concordance with treatment guidelines were identified using Poisson regression analysis. RESULTS: About 83% of colon and 56% of rectal cancer patients received recommended treatment. Provision of neo-adjuvant/adjuvant therapies may be less than optimal. Radiotherapy was less likely among older patients (prevalence ratio 0.7, 95% confidence interval 0.5-0.8). Chemotherapy was less likely among older patients (0.7, 0.6-0.8), those with severe or multiple co-morbidities (0.8, 0.7-0.9), and those from rural areas (0.9, 0.8-1.0). Overall discordance with treatment guidelines was more likely among rectal cancer patients (3.0, 2.7-3.3), older patients (1.6, 1.4-1.8), those with multiple co-morbid conditions (1.3, 1.1-1.4), and those living in rural areas (1.2, 1.0-1.3). CONCLUSIONS: Greater emphasis should be given to ensure CRC patients who may benefit from neo-adjuvant/adjuvant therapies have access to these treatments.

Do breast cancer risk factors differ among those who do and do not undertake mammography screening?

OBJECTIVES: There is considerable interest in whether mammography screening leads to over-diagnosis of breast cancer. However self-selection into screening programmes may lead to risk differences that affect estimates of over-diagnosis. This study compares the breast cancer risk profiles of participants and non-participants of population-based mammography screening. Risk profiles are also compared between those who have and have not used private screening services. SETTING: This study involved 1162 women aged 40-84 who participated in the 2012 Health Omnibus, an annual face-to-face interview-based survey of a representative sample of the population in the state of South Australia. METHODS: Data were collected on participation in mammography screening, demographic characteristics and breast cancer risk factors (including reproductive, familial and lifestyle factors). Missing data were multiply imputed. Factors independently associated with ever having been screened were identified using multivariable logistic regression, for population-based and ad hoc, private mammography screening separately. RESULTS: Compared with non-participants, participants of population-based screening were more likely to have used hormone replacement therapy (odds ratio [OR] = 3.72), experienced breast biopsy or surgery (OR = 2.22), and be overweight or obese (OR = 1.57). They were less likely to be sufficiently active (OR = 0.57) or be born in a non-English speaking country (OR = 0.50) or aged under 50 (OR = 0.09). Women who were screened privately were more likely to have a family history of breast cancer (OR = 1.66) and have experienced breast biopsy or surgery (OR = 3.17) than those who had not. CONCLUSIONS: South Australian women who participated in the population-based mammography screening have a slightly higher prevalence of breast cancer risk factors. This also applies to those who undertook private screening.

Impact of hormone replacement therapy use on mammographic screening outcomes.

PURPOSE: This study aims to measure the impact of HRT use at the time of screening on rates of screen-detected invasive breast cancer (IBC) and ductal carcinoma in situ (DCIS), interval cancers and investigative procedures, within a well-established population-based mammography screening program. METHODS: Using South Australian BreastScreen data from 1998 to 2009 pertaining to 819,722 screening episodes, Poisson regression models were undertaken to estimate the incidence risk ratios (IRR) for various screening outcomes at both the first and subsequent screening rounds, among women who had been using HRT in the 6 months prior to screening compared with those who had not. RESULTS: Current HRT use was associated with increased risk of recall for assessment, biopsy procedures, and breast cancer diagnosis among BreastScreen participants. Risk of screen-detected breast cancer was increased at subsequent screening rounds (IRR = 1.30, 95% confidence interval 1.18-1.34), but not at women's first screening round (1.05, 0.88-1.25). This increased risk applied to IBC (1.35, 1.27-1.45), but not to DCIS (1.04, 0.89-1.23). Interval cancer risk was elevated among HRT users following both the first screen (1.77, 1.33-2.37) and subsequent screening episodes (1.92, 1.72-2.15). CONCLUSIONS: Increased risks of recall, biopsy rates, screen-detected, and interval cancers among HRT users have important implications for population-based breast cancer screening programs. Our findings support the concept that HRT use may increase the growth of preexisting cancers. Lack of effect on DCIS could imply different etiology or time frames for DCIS and IBC development or increased transition from preinvasive to invasive disease due to HRT use.

Surgical margins and risk of locoregional recurrence in invasive breast cancer: an analysis of 10-year data from the Breast Cancer Treatment Quality Assurance Project.

AIM: There is debate as to what constitutes an adequate excision margin to reduce the risk of locoregional recurrence (LRR) after breast cancer surgery. We have investigated the relationship between surgical margin distance and LRR in women with invasive breast cancer (IBC). METHODS: Tumour free margin distances were extracted from histopathology reports for women with IBC, treated by either breast conserving surgery or mastectomy, enrolled in the Breast Cancer Treatment Group Quality Assurance Project from July 1997 to June 2007. Cox proportional hazards regression analyses were conducted to compare the risk of LRR for involved margins compared with negative margins, measured in increments rounded to the nearest mm. RESULTS: 88 of 2300 patients (3.8%) experienced an LRR after a mean follow-up of 7.9 years. An involved margin, or a margin of 1 mm was associated with an increased risk of LRR (HR 2.72, 95% CI 1.30-5.69), whilst margin distances of 2 mm or greater were not. Risk of LRR with margin distances <2 mm was particularly high amongst those not receiving radiotherapy (RT). CONCLUSION: Based on our findings, we recommend that a tumour free margin distance of 2 mm be adopted as an adequate margin of excision for IBC, in the setting of patients receiving standard adjuvant RT and adjuvant drug therapies as dictated by the current clinical treatment paradigms.

Variation in the management of early breast cancer in rural and metropolitan centres: implications for the organisation of rural cancer services.

The study examines the management and outcomes of women with early invasive breast cancer treated in rural and metropolitan centres over a nine-year observation period. A prospective audit of the treatment and outcomes of 2081 women with early breast cancer who underwent potentially curative surgery between 1997 and 2006 in metropolitan Canberra or in the surrounding rural region was completed. Overall, there was good agreement between published guidelines and the treatment received by the women in the study. However, women treated in rural centres were less likely to receive postoperative radiotherapy after breast-conserving surgery, or to undergo axillary lymph node surgery or sentinel lymph node biopsy compared with women treated in metropolitan centres. Surgery in a rural centre was associated with increased breast cancer recurrence (HR = 1.54, p < 0.001) and increased breast cancer mortality (HR = 1.84, p < 0.001), after adjustment for age and tumour characteristics. Non-cancer related mortality was increased in women treated in rural centres compared with women travelling to a metropolitan centre for surgery (HR = 2.08; p = 0.005). There were differences in both the care provided and treatment outcomes between women treated in rural centres and women treated in metropolitan centres. However, the increased non-cancer related mortality in women treated in rural centres suggests an increased medical comorbidity in this group. Initiatives supporting rural-based surgeons to adopt new procedures such as sentinel node biopsy may help to optimise rural breast cancer treatment.

Patient and carer perceptions of cancer care in South Australia.

Quality of care from the patient's perspective is an increasingly important outcome measure for cancer services. Patients' and carers' perceptions of cancer care were assessed through structured telephone interviews, 4-10 months post-discharge, which focused on experiences during the most recent hospital admission. A total of 481 patients with a primary diagnosis of cancer (ICD-10 C codes) were recruited, along with 345 carers nominated by the patients. Perceptions of clinical care were generally positive. Less positive aspects of care included not being asked how they were coping, not being offered counselling, and not receiving written information about procedures. Results also highlighted inadequate discharge processes. Carers were more likely than patients to report negative experiences. Perceptions of care also differed by cancer type.

Supporting cancer control for Indigenous Australians: initiatives and challenges for cancer councils.

As in other developed countries, the Australian population is ageing, and cancer rates increase with age. Despite their substantially lower life expectancy, Indigenous Australians are also experiencing concerning cancer statistics, characterised by increasing rates, later diagnosis, higher mortality, and lower participation in screening than the non-Indigenous population. Eighteen months after the first national Indigenous Cancer Control Forum, this environmental scan within the state-based Cancer Councils was undertaken to map activities in service provision in Indigenous cancer control with a view to sharing the lessons learned. The findings show that although most of the organisations had tried to work with Indigenous communities on cancer issues, there have been difficulties in building and sustaining relationships with Indigenous organisations. Lack of having Indigenous staff internally, few Indigenous-specific resources, and few planned, long-term commitments were some of the major impediments. Some of these limitations can easily be overcome by building and improving regional or local partnerships, providing cultural awareness training to internal staff, and by building the capacity of Indigenous organisations. Health promotion projects of the Cancer Councils directed at Indigenous people could be more effectively implemented with such considerations.