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Refereed/Peer-reviewed 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

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.

Objectives To summarize debate and research in the Swedish Two-County Trial of mammographic screening on key issues of trial design, endpoint evaluation, and overdiagnosis, and from these to infer promising directions for the future. Methods A cluster-randomized controlled trial of the offer of breast cancer screening in Sweden, with a single screen of the control group at the end of the screening phase forms the setting for a historical review of investigations and debate on issues of design, analysis, and interpretation of results of the trial. Results There has been considerable commentary on the closure screen of the control group, ascertainment of cause of death, and cluster randomization. The issues raised were researched in detail and the main questions answered in publications between 1989 and 2003. Overdiagnosis issues still remain, but methods of estimation taking full account of lead time and of non-screening influences on incidence (taking place mainly before 2005) suggest that it is a minor phenomenon. Conclusion Despite resolution of issues relating to this trial in peer-reviewed publications dating from years, or even decades ago, issues that already have been addressed continue to be raised. We suggest that it would be more profitable to concentrate efforts on current research issues in breast cancer diagnosis, treatment, and prevention.

Background Prostate cancer can be treated with several different modalities, including radiation treatment. Various prognostic tools have been developed to aid decision making by providing estimates of the probability of different outcomes. Such tools have been demonstrated to have better prognostic accuracy than clinical judgment alone. Methods A systematic review was undertaken to identify papers relating to the prediction of clinical outcomes (biochemical failure, metastasis, survival) in patients with prostate cancer who received radiation treatment, with the particular aim of identifying whether published tools are adequately developed, validated, and provide accurate predictions. PubMed and EMBASE were searched from July 2007. Title and abstract screening, full text review, and critical appraisal were conducted by two reviewers. A review protocol was published in advance of commencing literature searches. Results The search strategy resulted in 165 potential articles, of which 72 were selected for full text review and 47 ultimately included. These papers described 66 models which were newly developed and 31 which were external validations of already published predictive tools. The included studies represented a total of 60,457 patients, recruited between 1984 and 2009. Sixty five percent of models were not externally validated, 57% did not report accuracy and 31% included variables which are not readily accessible in existing datasets. Most models (72, 74%) related to external beam radiation therapy with the remainder relating to brachytherapy (alone or in combination with external beam radiation therapy). Conclusions A large number of prognostic models (97) have been described in the recent literature, representing a rapid increase since previous reviews (17 papers, 1966–2007). Most models described were not validated and a third utilised variables which are not readily accessible in existing data collections. Where validation had occurred, it was often limited to data taken from single institutes in the US. While validated and accurate models are available to predict prostate cancer specific mortality following external beam radiation therapy, there is a scarcity of such tools relating to brachytherapy. This review provides an accessible catalogue of predictive tools for current use and which should be prioritised for future validation. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0786-z) contains supplementary material, which is available to authorized users.

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. Refereed/Peer-reviewed

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. Refereed/Peer-reviewed

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. Refereed/Peer-reviewed

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

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. Refereed/Peer-reviewed

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. Refereed/Peer-reviewed

Background: Inequalities in survival from colorectal cancer (CRC) across socioeconomic groups and by area ofresidence have been described in various health care settings. Few population-wide datasets which includeclinical and treatment information are available in Australia to investigate disparities. This study examinessocio-demographic differences in survival for CRC patients in South Australia (SA), using a population-widedatabase derived via linkage of administrative and surveillance datasets. Methods: The study population comprised all cases of CRC diagnosed in 2003-2008 among SA residentsaged 50-79 yrs in the SA Central Cancer Registry. Measures of socioeconomic status (area level), geographicalremoteness, clinical characteristics, comorbid conditions, treatments and outcomes were derived through recordlinkage 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 whichtime 1525 died from CRC and 416 died from other causes. Results of competing risk regression indicated higher risk ofCRC 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 leastadvantaged areas (HR =0.75, 95 % 0.62-0.91). Patients residing in remote locations had significantly worse outcomes thanmetropolitan 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 havinga universal health care system. Of particular concern is the poorer survival for patients from remote areas withpotentially curable CRC. Reasons for these disparities require further exploration to identify factors that can beaddressed to improve outcomes. Refereed/Peer-reviewed