Prostate Cancer Related Sexual Dysfunction and Barriers to Help Seeking: A Scoping Review.

OBJECTIVE: Despite available support, sexuality needs are the most frequently reported unmet need among men with prostate cancer, which may be due to low help-seeking rates. Using the Ecological Systems Framework as a theoretical foundation, we conducted a scoping review of the available literature to understand what factors impact help-seeking behaviour for sexual issues after prostate cancer treatment among men who had received treatment. METHODS: Following PRISMA guidelines, a systematic search on Medline, PsychInfo, Embase, Emcare, and Scopus was conducted to identify studies of adult prostate cancer patients post-treatment, which reported barriers and/or facilitators to help-seeking for sexual health issues. Quality appraisals were conducted using Joanna Briggs Institute appraisal tools, and results were qualitatively synthesised. RESULTS: Of the 3870 unique results, only 30 studies met inclusion criteria. In general, studies were considered moderate to good quality, though only six used standardised measures to assess help-seeking behaviour. Barriers and facilitators for sexual help-seeking were identified across all five levels of the Ecological Systems Framework, including age, treatment type, and previous help seeking experience (individual level), healthcare professional communication and partner support (microsystem), financial cost and accessibility of support (meso/exosystem), and finally embarrassment, masculinity, cultural norms, and sexuality minority (macrosystem). CONCLUSIONS: Addressing commonly reported barriers (and inversely, enhancing facilitators) to help-seeking for sexual issues is essential to ensure patients are appropriately supported. Based on our results, we recommend healthcare professionals include sexual wellbeing discussions as standard care for all prostate cancer patients, regardless of treatment received, age, sexual orientation, and partnership status/involvement.

Temporal trends in medication and service use patterns for mental health issues among men with prostate cancer.

OBJECTIVE: Prostate cancer can significantly impact mental wellbeing, creating uncertainty and morbidity. This study described patterns of psychotropic medication and mental health service use, as a proxy measure for mental health problems, 5 years before and 5 years after prostate cancer diagnosis. METHODS: Population-based registry data were linked with Pharmaceutical Benefits Scheme and Medicare Benefits Schedule data for all prostate cancer patients diagnosed in South Australia between 2012 and 2020 (n = 13,693). We estimated the proportion and rates of psychotropic medication and mental health service use before and after diagnosis. Multivariable adjusted interrupted time series analyses (ITSA) were conducted to uncover temporal patterns. RESULTS: Fifteen percent of men commenced psychotropic medications and 6.4% sought out mental health services for the first time after diagnosis. Psychotropic medication use rose from 34.5% 5 years before to 40.3% 5 years after diagnosis, including an increase in use of antidepressants (from 20.7% to 26.0%) and anxiolytics (from 11.3% to 12.8%). Mental health service use increased from 10.2% to 12.1%, with the increase mostly being general practice mental health visits (from 7.8% to 10.6%). Multivariable ITSA indicated a significant rise in medication and service utilisation immediately before and in the first 2 years following prostate cancer diagnosis. CONCLUSION: There is a clear increase in psychotropic medication use and mental health service use around the time of prostate cancer diagnosis. Mental health outcomes of men with prostate cancer may be improved with early mental health screening, particularly during the diagnosis process, to enable early intervention.

Communicating prostate cancer outcomes data to consumers A brief communication.

OBJECTIVE: To translate and communicate outcomes data for prostate cancer from a clinical registry data into a consumer-friendly resource. METHODS: First, we analyzed real-world data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) registry for men diagnosed from 2008 to 2018 including clinical and functional outcomes following surgery, external beam radiotherapy, brachytherapy, hormone therapy, active surveillance and watchful waiting. These outcomes included overall survival, cancer specific survival, biochemical recurrence, decline in functional outcomes, and transition to active treatment following active surveillance. Second, we translated outcomes into a summary text and pictographic format and present in one document that consumers found easy to understand and interpret. This "Prostate Cancer Outcomes Report Card" was developed in consultation with a consumer advisory group and further improved through exploratory interviews with people affected by prostate cancer, an online survey among the general public, and clinician feedback. RESULTS: The 5-year prostate cancer-specific survival rate was 97%. There is a reasonably high chance of cancer returning within 5 years (17% after surgery and 14% after radiotherapy) while 1 in 3 men on active surveillance transitioned to other treatments within 5 years. Sexual function was negatively affected following all treatment types. Men with higher risk disease had a worse prognosis, a higher chance of recurrence and greater decline in physical function. Consumers required trustworthy, comprehensive, simple and up-to-date information collated in one place, and valued having access to this resource. Data on high survival rates were considered reassuring. There were high levels of unmet psychosocial and supportive care needs, especially in relation to mental health and sexual function. The report card was well received by patients and health care workers. CONCLUSIONS: This relatively simple and easily understandable consumer-oriented outcome report serves to better inform men with prostate cancer and facilitate patient-provider communication and shared decision-making.

Impact of comorbidities on prostate cancer-specific mortality: A population-based cohort study.

AIM: To assess the impact of comorbidities on prostate cancer mortality. METHODS: We studied 15,695 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked data sets. Comorbidity was measured 1-year before prostate cancer diagnosis using Rx-Risk, a medication-based comorbidity index. Flexible parametric competing risk regression was used to estimate the independent association between comorbidities and prostate cancer-specific mortality. Specific common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and pain) were also assessed to determine their association with mortality. All models were adjusted for sociodemographic variables, tumor characteristics, and treatment type. RESULTS: Prostate cancer-specific mortality was higher for patients with a Rx-Risk score ≥3 versus 0 (adjusted sub-hazard ratio (sHR) 1.34, 95% CI: 1.15-1.56). Lower comorbidity scores (Rx-Risk score 2 vs. 0 and Rx-Risk score 1 vs. 0) were not significantly associated with prostate cancer-specific mortality. Men who were using medications for cardiac disorders (sHR 1.31, 95% CI: 1.13-1.52), chronic airway disease (sHR 1.20, 95% CI: 1.01-1.44), depression and anxiety (sHR 1.17, 95% CI: 1.02-1.35), and thrombosis (sHR 1.21, 95% CI: 1.04-1.42) were at increased risk of dying from prostate cancer compared with men not on those medications. Use of medications for diabetes and chronic pain were not associated with prostate cancer-specific mortality. All Rx-Risk score categories and the specific comorbidities were also associated with increased risk of all-cause mortality. CONCLUSION: The findings showed that ≥3 comorbid conditions and specific comorbidities including cardiac disease, chronic airway disease, depression and anxiety, and thrombosis were associated with poor prostate cancer-specific survival. Appropriate management of these comorbidities may help to improve survival in prostate cancer patients.

Medication-based Comorbidity Measures and Prostate Cancer Treatment Selection.

INTRODUCTION: We aimed to assess the association between comorbidities and prostate cancer management. PATIENTS AND METHODS: We studied 12,603 South Australian men diagnosed with prostate cancer between 2003 and 2019. Comorbidity was measured one year prior to prostate cancer diagnosis using a medication-based comorbidity index (Rx-Risk). Binomial logistic regression analyses were used to assess the association between comorbidities and primary treatment selection (active surveillance, radical prostatectomy (RP), external beam radiotherapy (EBRT) with or without androgen deprivation therapy (ADT), brachytherapy, ADT alone, and watchful waiting (WW)). Certain common comorbidities within Rx-Risk (cardiac disorders, diabetes, chronic airway diseases, depression and anxiety, thrombosis, and chronic pain) were also assessed. All models were adjusted for sociodemographic and tumor characteristics. RESULTS: Likelihood of receiving RP was lower among men with Rx-Risk score ≥3 (odds ratio (OR) 0.62, 95%CI:0.56-0.69) and Rx-Risk 2 (OR 0.80, 95%CI:0.70-0.92) compared with no comorbidity (Rx-Risk ≤0). Men with high comorbidity (Rx-Risk ≥3) were more likely to have received ADT alone (OR 1.76, 95%CI:1.40-2.21), EBRT (OR 1.30, 95%CI:1.17-1.45) or WW (OR 1.49, 95%CI:1.19-1.88) compared with Rx-Risk ≤0. Pre-existing cardiac and respiratory disorders, thrombosis, diabetes, depression and anxiety, and chronic pain were associated with lower likelihood of selecting RP and higher likelihood of EBRT (except chronic airway disease) or WW (except diabetes and depression and anxiety). Cardiac disorders and thrombosis were associated with higher likelihood of selecting ADT alone. Furthermore, age had greater effect on treatment choice than the level of comorbidity. CONCLUSION: High comorbidity burden was associated with primary treatment choice, with significantly less RP and more EBRT, WW and ADT alone among men with higher levels of comorbidity. Each of the individual comorbid conditions also influenced treatment selection.

Clinical and functional outcomes for risk-appropriate treatments for prostate cancer.

Objectives: To describe real-world clinical and functional outcomes in an Australian cohort of men with localised prostate cancer according to treatment type and risk category. Subjects and methods: Men diagnosed from 2008 to 2018 who were enrolled in South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a multi-institutional prospective clinical registry-were studied. The main outcome measures were overall survival, cancer-specific survival, decline in functional outcomes, biochemical recurrence and transition to active treatment following active surveillance. Multivariable adjusted models were applied to estimate outcomes. Results: Of the 8513 eligible men, majority of men (46%) underwent radical prostatectomy (RP) followed by external beam radiation therapy with or without androgen deprivation therapy (EBRT +/- ADT) in 22% of the cohort. Five-year overall survival was above 91%, and 5-year prostate cancer-specific survival was above 97% in the low- and intermediate-risk categories across all treatments. Five-year prostate cancer-specific survival in the active surveillance group was 100%. About 37% of men with high-risk disease treated with RP and 17% of men treated with EBRT +/- ADT experienced biochemical recurrence within 5 years of treatment. Of men on active surveillance, 15% of those with low risk and 20% with intermediate risk converted to active treatment within 2 years. The decline in urinary continence and sexual function 12 months after treatment was greatest among men who underwent RP while the decline in bowel function was greatest for men who received EBRT +/- ADT. Conclusion: This contemporary real-world evidence on risk-appropriate treatment outcomes helps inform treatment decision-making for clinicians and patients.

Utility of prescription-based comorbidity indices for predicting mortality among Australian men with prostate cancer.

BACKGROUND: Drug prescription registries has become an alternative data source to hospital admission databases for measuring comorbidities. However, the predictive validity of prescription-based comorbidity measures varies based on the population under investigation and outcome of interest. We aimed to determine which prescription-based index of comorbidity has most utility in Australian men with prostate cancer. METHODS: We studied 25,414 South Australian men diagnosed with prostate cancer between 2003 and 2019 from state-wide administrative linked datasets. The Rx-Risk index, Chronic Disease Score (CDS), Drug Comorbidity Index (DCI) and Pharmaceutical Prescribing Profile (P3) with one year lookback period from prostate cancer diagnosis were evaluated. The predictive ability of each index to determine all-cause deaths within two and five years of prostate cancer diagnosis was compared using the c-statistic from flexible parametric survival models, adjusting for age, socioeconomic status and year of prostate cancer diagnosis. RESULTS: The Rx-Risk index performed better in predicting two-year (c-statistic = 0.818) and five-year (c-statistic = 0.784) all-cause mortality than P3, CDS and DCI. Including comorbidity measures as continuous scores resulted in a better performance than including them as categories. Grouping scores into four categories (≤0, >0 - ≤1, >1 - ≤2, and >2) resulted in better performance and calibration than using fewer categories. CONCLUSION: Rx-Risk was validated in Australia and reflects Australian prescribing patterns. It showed better predictive performance for mortality in our study, with a modest improvement over P3, CDS and DCI. For research with prostate cancer populations, we recommend the use of drug-based comorbidity indices that have been validated in a similar population.

Risk of secondary malignancy following radiation therapy for prostate cancer.

We investigated whether prostate cancer patients treated with external beam radiation therapy (EBRT) have a higher cumulative incidence of secondary cancer compared with patients treated with radical prostatectomy (RP). We used state-wide linked data from South Australia to follow men with prostate cancer diagnosed from 2002 to 2019. The cumulative incidence of overall and site-specific secondary cancers between 5 and 15 years after treatment was estimated. Fine-Gray competing risk analyses were performed with additional sensitivity analyses to test different scenarios. A total of 7625 patients were included (54% underwent RP and 46% EBRT). Characteristics of the two groups differed significantly, with the EBRT group being older (71 vs. 64 years), having higher comorbidity burden and being more likely to die during follow-up than the RP group. Fifteen-year cumulative incidence for all secondary cancers was 27.4% and 22.3% in EBRT and RP groups, respectively. In the adjusted models, patients in the EBRT group had a significantly higher risk of genitourinary (adjusted subhazard ratio (aSHR), 2.29; 95%CI 1.16-4.51) and lung (aSHR, 1.93; 95%CI 1.05-3.56) cancers compared with patients in the RP group. However, there was no statistically significant difference between the two groups for risk of any secondary cancer, gastro-intestinal, skin or haematologic cancers. No statistically significant differences in overall risk of secondary cancer were observed in any of the sensitivity analyses and patterns for risk at specific cancer sites were relatively consistent across different age restriction and latency/time-lag scenarios. In conclusion, the increased risk of genitourinary and lung cancers among men undergoing EBRT may relate partly to treatment effects and partly to unmeasured residual confounding.

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.

Development of the consensus-based recommendations for Podiatry care of Neuropathy In Cancer Survivors (PodNICS): a Delphi consensus study of Australian podiatrists.

BACKGROUND: Chemotherapy Induced Peripheral Neuropathy (CIPN) is the most common presenting side effect of chemotherapy. As a sensory based neuropathy, this condition can persist for a long time after cessation of chemotherapy and impact the quality of life of cancer survivors. Podiatrists in Australia have been managing people with CIPN related lower limb complications, however guidelines on management of CIPN do not exist. The aim of this study was to achieve consensus and agreement of Australian podiatrists on strategies to best manage people presenting with symptoms of CIPN. METHODS: An online three-round modified Delphi survey of Australian podiatrists with expertise in CIPN was conducted in line with recommendations for conducting and reporting of Delphi studies (CREDES). Panellists responded to open-ended questions in Round 1, whereupon their responses were themed into statements and analysed for existing consensus. Statements not reaching consensus were returned during Round 2 to seek agreement from responders using a five-point Likert scale and to allow responders to make further comments. For a statement to reach consensus or agreement, 70% or more of panellists needed to make the same comment or agree or strongly agree with the same themed statement. Statements reaching 50 to 69% consensus or agreement were returned to panellists in Round 3 for them to consider their responses in the light of group outcomes. RESULTS: Round one resulted in 229 comments from 21 of 26 podiatrists who agreed to participate. These comments were themed into 53 statements with 11 consensus statements accepted. Round 2 resulted in 22 statements reaching agreement, and 15 new statements being generated from 18 comments made by 17 respondents. Round 3 resulted in 11 statements reaching agreement. Outcomes were developed into a set of clinical recommendations for diagnosis and management of people presenting with CIPN. These recommendations provide guidance on 1) identifying common signs and symptoms of CIPN including sensory, motor and autonomic symptoms; 2) diagnosis and assessment of CIPN including neurological, motor and dermatological assessment modalities; and 3) best clinical practice and management strategies for CIPN identified by podiatrists including both podiatry and non-podiatry specific care. CONCLUSIONS: This is the first study in podiatry literature to develop expert-informed consensus-based recommendations for clinical presentation, diagnosis and assessment and management of people with CIPN. These recommendations aim to help guide podiatrists in the consistent care of people with CIPN.

Factors impacting on sexual function among men on active surveillance for prostate cancer.

BACKGROUND: Active surveillance (AS) aims to reduce overtreatment and minimize the negative side effects of radical therapies (i.e., prostatectomy or radiotherapy) while preserving quality of life. However, a substantial proportion of men can experience a decline in sexual function during AS follow-up. The aim of this study was to identify predictors of declining sexual function among men on AS. METHODS: Men enrolled from 2008 to 2018 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry-a prospective clinical registry-were studied. Sexual function outcomes were measured using expanded prostate cancer index composite (EPIC-26) at baseline and 12-months postdiagnosis. Multivariable regression models adjusted for baseline score and other sociodemographic and clinical factors were applied to identify predictors of sexual function score at 12-months. RESULTS: A total of 554 men were included. Variables that showed significant association with decline in sexual function score at 12-months were: having two or more biopsies after diagnosis (mean change score (MCS): -16.3, p < 0.001) compared with no biopsy, higher number of positive biopsy cores (MCS: -1.6, p = 0.004), being in older age category (above 70 vs. below 60: MCS: -16.7, p < 0.001; 65-70 vs. below 60: MCS: -9.7, p = 0.024), having had depression (MCS: -9.0, p = 0.020), and impaired physical function (MCS: -10.0, p = 0.031). Greater socioeconomic advantage (highest vs. lowest quintile: MCS: 15.7, p = 0.022) and year of diagnosis (MCS: 2.6 for every year, p < 0.001) were positively associated with 12-months sexual function score. Neither biopsy type, biopsy timing nor PSA velocity were associated with declines in sexual function. CONCLUSIONS: Our findings suggest that multiple factors affected sexual function during AS. Interventions toward reducing the number of biopsies through less invasive monitory approaches, screening for physical and mental well-being, and targeted emotional support and counseling services may be helpful for men on AS.

Developing a consensus statement for psychosocial support in active surveillance for prostate cancer.

Purpose: Our objective was to prioritise the psychosocial support needs of men on active surveillance for prostate cancer and to develop a consensus statement to provide guidance on best practice psychosocial support for men choosing active surveillance and their families. Subjects and methods: We undertook a patient and public involvement Delphi process over two rounds, informed by qualitative data and a comprehensive literature review, to prioritise the information and support needs of men on active surveillance for prostate cancer. Two panels were surveyed, a patient/carer panel (n = 55) and a health care provider panel (n = 114). Based on the findings of the Delphi surveys, an expert active surveillance discussion group developed a consensus statement to guide best practice. Results: Patients and health care professionals differed slightly in their ideas concerning priorities for active surveillance psychosocial support. Broadly, agreed priority areas included -patients being involved in decision-making, continuity of care, more streamlined access to health care teams, improved understanding of the risk of prostate cancer progression and information and support provided through both health care professionals and peers. Based on the identified priorities, the expert discussion group agreed on 22 consensus statements for best practice in psychosocial care for active surveillance in respect of (1) principles of an active surveillance programme; (2) structure of consultations; (3) content of information and support; and (4) delivery of information. Conclusion: This consensus statement provides a framework for patient-focused psychosocial support, which, if adopted, should increase uptake and adherence to active surveillance among men with prostate cancer.

Choice of imputation method for missing metastatic status affected estimates of metastatic prostate cancer incidence.

OBJECTIVES: To study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer. STUDY DESIGN AND SETTING: Estimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage. RESULTS: The proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage. CONCLUSIONS: Plausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI.

Risk of progression following a negative biopsy in prostate cancer active surveillance.

BACKGROUND: Currently, follow-up protocols are applied equally to men on active surveillance (AS) for prostate cancer (PCa) regardless of findings at their initial follow-up biopsy. To determine whether less intensive follow-up is suitable following negative biopsy findings, we assessed the risk of converting to active treatment, any subsequent upgrading, volume progression (>33% positive cores), and serious upgrading (grade group >2) for negative compared with positive findings on initial follow-up biopsy. METHODS: 13,161 men from 24 centres participating in the Global Action Plan Active Surveillance Prostate Cancer [GAP3] consortium database, with baseline grade group ≤2, PSA ≤ 20 ng/mL, cT-stage 1-2, diagnosed after 1995, and ≥1 follow-up biopsy, were included in this study. Risk of converting to treatment was assessed using multivariable mixed-effects survival regression. Odds of volume progression, any upgrading and serious upgrading were assessed using mix-effects binary logistic regression for men with ≥2 surveillance biopsies. RESULTS: 27% of the cohort (n = 3590) had no evidence of PCa at their initial biopsy. Over 50% of subsequent biopsies in this group were also negative. A negative initial biopsy was associated with lower risk of conversion (adjusted hazard ratio: 0.45; 95% confidence interval [CI]: 0.42-0.49), subsequent upgrading (adjusted odds ratio [OR]: 0.52; 95%CI: 0.45-0.62) and serious upgrading (OR: 0.74; 95%CI: 0.59-92). Radiological progression was not assessed due to limited imaging data. CONCLUSION: Despite heterogeneity in follow-up schedules, findings from this global study indicated reduced risk of converting to treatment, volume progression, any upgrading and serious upgrading among men whose initial biopsy findings were negative compared with positive. Given the low risk of progression and high likelihood of further negative biopsy findings, consideration should be given to decreasing follow-up intensity for this group to reduce unnecessary invasive biopsies.

Patient-reported functional outcome measures and treatment choice for prostate cancer.

BACKGROUND: The aim of this study was to describe changes in patient-reported functional outcome measures (PROMs) comparing pre-treatment and 12 months after radical prostatectomy (RP), external beam radiation therapy (EBRT), brachytherapy and active surveillance (AS). METHODS: Men enrolled from 2010 to 2019 in the South Australian Prostate Cancer Clinical Outcomes Collaborative registry a prospective clinical registry were studied. Urinary, bowel, and sexual functions were measured using Expanded Prostate Cancer Index Composite (EPIC-26) at baseline and 12 months post-treatment. Higher scores on the EPIC-26 indicate better function. Multivariable regression models were applied to compare differences in function and extent of bother by treatment. RESULTS: Of the 4926 eligible men, 57.0% underwent RP, 20.5% EBRT, 7.0% brachytherapy and 15.5% AS. While baseline urinary and bowel function varied little across treatment groups, sexual function differed greatly (adjusted mean scores: RP = 56.3, EBRT = 45.8, brachytherapy = 61.4, AS = 52.8; p < 0.001). Post-treatment urinary continence and sexual function declined in all treatment groups, with the greatest decline for sexual function after RP (adjusted mean score change - 28.9). After adjustment for baseline differences, post-treatment sexual function scores after EBRT (6.4; 95%CI, 0.9-12.0) and brachytherapy (17.4; 95%CI, 9.4-25.5) were higher than after RP. Likewise, urinary continence after EBRT (13.6; 95%CI, 9.0-18.2), brachytherapy (10.6; 95%CI, 3.9-17.3) and AS (10.6; 95%CI, 5.9-15.3) were higher than after RP. Conversely, EBRT was associated with lower bowel function (- 7.9; 95%CI, - 12.4 to - 3.5) than RP. EBRT and AS were associated with lower odds of sexual bother (OR 0.51; 95%CI, 0.29-0.89 and OR 0.60; 95%CI, 0.38-0.96, respectively), and EBRT with higher odds of bowel bother (OR 2.01; 95%CI, 1.23-3.29) compared with RP. CONCLUSION: The four common treatment approaches for prostate cancer were associated with different patterns of patient-reported functional outcomes, both pre- and 12 months post-treatment. However, after adjustment, RP was associated with a greater decline in urinary continence and sexual function than other treatments. This study underscores the importance of collecting baseline PROMs to interpret post-treatment functional outcomes.

Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis.

OBJECTIVE: To determine if margin involvement is associated with distant recurrence and to determine the required margin to minimise both local recurrence and distant recurrence in early stage invasive breast cancer. DESIGN: Prospectively registered systematic review and meta-analysis of literature. DATA SOURCES: Medline (PubMed), Embase, and Proquest online databases. Unpublished data were sought from study authors. ELIGIBILITY CRITERIA: Eligible studies reported on patients undergoing breast conserving surgery (for stages I-III breast cancer), allowed an estimation of outcomes in relation to margin status, and followed up patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or treated with neoadjuvant chemotherapy or by mastectomy were excluded. Where applicable, margins were categorised as tumour on ink (involved), close margins (no tumour on ink but <2 mm), and negative margins (≥2 mm). RESULTS: 68 studies from 1 January 1980 to 31 December 2021, comprising 112 140 patients with breast cancer, were included. Across all studies, 9.4% (95% confidence interval 6.8% to 12.8%) of patients had involved (tumour on ink) margins and 17.8% (13.0% to 23.9%) had tumour on ink or a close margin. The rate of distant recurrence was 25.4% (14.5% to 40.6%) in patients with tumour on ink, 8.4% (4.4% to 15.5%) in patients with tumour on ink or close, and 7.4% (3.9% to 13.6%) in patients with negative margins. Compared with negative margins, tumour on ink margins were associated with increased distant recurrence (hazard ratio 2.10, 95% confidence interval 1.65 to 2.69, P<0.001) and local recurrence (1.98, 1.66 to 2.36, P<0.001). Close margins were associated with increased distant recurrence (1.38, 1.13 to 1.69, P<0.001) and local recurrence (2.09, 1.39 to 3.13, P<0.001) compared with negative margins, after adjusting for receipt of adjuvant chemotherapy and radiotherapy. In five studies published since 2010, tumour on ink margins were associated with increased distant recurrence (2.41, 1.81 to 3.21, P<0.001) as were tumour on ink and close margins (1.44, 1.22 to 1.71, P<0.001) compared with negative margins. CONCLUSIONS: Involved or close pathological margins after breast conserving surgery for early stage, invasive breast cancer are associated with increased distant recurrence and local recurrence. Surgeons should aim to achieve a minimum clear margin of at least 1 mm. On the basis of current evidence, international guidelines should be revised. SYSTEMATIC REVIEW REGISTRATION: CRD42021232115.

Antibodies as biomarkers for cancer risk: a systematic review.

Increasing evidence has linked the humoral immune response with the development of various cancers. Therefore, there is growing interest in investigating the predictive value of antibodies to assess overall and tissue site-specific cancer risk. Given the large amount of antibody types and the broad scope of the search (i.e. cancer risk), the primary aim of this systematic review was to present an overview of the most researched antibodies (i.e. immunoglobulin (Ig) isotypes (IgG, IgM, IgA, and IgE), tumour and self-antigen-reactive antibodies, infection-related antibodies) in relation to overall and site-specific cancer risk. We identified various antibody types that have been associated with the risk of cancer. While no significant associations were found for IgM serum levels, studies found an inconsistent association among IgE, IgA, and IgG serum levels in relation to cancer risk. When evaluating antibodies against infectious agents, most studies reported a positive link with specific cancers known to be associated with the specific agent recognized by serum antibodies (i.e. helicobacter pylori and gastric cancer, hepatitis B virus and hepatocellular carcinoma, and human papillomavirus and cervical cancer). Several reports identified autoantibodies, as single biomarkers (e.g. anti-p53, anti-MUC1, and anti-CA125) but especially in panels of multiple autoantibodies, to have potential as diagnostic biomarkers for specific cancer types. Overall, there is emerging evidence associating certain antibodies to cancer risk, especially immunoglobulin isotypes, tumour-associated antigen-specific, and self-reactive antibodies. Further experimental studies are necessary to assess the efficacy of specific antibodies as markers for the early diagnosis of cancer.

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.

Changes in five-year survival for people with acute leukaemia in South Australia, 1980-2016.

OBJECTIVES: To examine population changes in 5-year survival for people in South Australia diagnosed with acute leukaemia during 1980-2016, by socio-demographic characteristics. DESIGN, SETTING: Retrospective analysis of South Australian Cancer Registry data for the period 1980-2016. PARTICIPANTS: All South Australian residents diagnosed with primary acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) during 1980-2016. MAIN OUTCOME MEASURES: 5-year disease-specific survival and disease-specific mortality. RESULTS: Crude 5-year disease-specific survival was 58% (95% CI, 54-61%) for the 1035 people diagnosed with ALL during 1980-2016, and 18% (95% CI, 17-20%) for the 2814 people diagnosed with AML. Survival improved steadily across the study period: from 44% (95% CI, 35-52%) for people with ALL diagnosed during 1980-1984 to 69% (95% CI, 63-75%) for those diagnosed during 2010-2016; and from 9% (95% CI, 5-15%) to 23% (95% CI, 20-26%) for people diagnosed with AML. Disease-specific mortality increased with age, but was not influenced by socio-economic status or remoteness of residence. After adjusting for other factors, rates of change in risk of leukaemia-related death were greater for younger than older patients with ALL (for interaction: P = 0.004) or AML (P = 0.005), but were not significantly influenced by socio-economic status or remoteness. CONCLUSION: Five-year survival for people with acute leukaemia in South Australia continuously improved during 1980-2016, and socio-economic status and remoteness did not influence survival. It improved markedly for younger patients (under 50 years of age). However, survival is still relatively poor, especially for people over 50 years with AML.