Active surveillance for prostate cancer: an update

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record. An increasing number of men diagnosed with localised prostate cancer has been accompanied by more men being considered for active surveillance as a management option. Here the author provides an update on recent developments in active surveillance and changes to NICE guidance

Prostate Cancer in Primary Care

This is the final version of the article. Available from Springer Verlag via the DOI in this record.Prostate cancer is a common malignancy seen worldwide. The incidence has risen in recent decades, mainly fuelled by more widespread use of prostate-specific antigen (PSA) testing, although prostate cancer mortality rates have remained relatively static over that time period. A man's risk of prostate cancer is affected by his age and family history of the disease. Men with prostate cancer generally present symptomatically in primary care settings, although some diagnoses are made in asymptomatic men undergoing opportunistic PSA screening. Symptoms traditionally thought to correlate with prostate cancer include lower urinary tract symptoms (LUTS), such as nocturia and poor urinary stream, erectile dysfunction and visible haematuria. However, there is significant crossover in symptoms between prostate cancer and benign conditions affecting the prostate such as benign prostatic hypertrophy (BPH) and prostatitis, making it very challenging to distinguish between them on the basis of symptoms. The evidence for the performance of PSA in asymptomatic and symptomatic men for the diagnosis of prostate cancer is equivocal. PSA is subject to false positive and false negative results, affecting its clinical utility as a standalone test. Clinicians need to counsel men about the risks and benefits of PSA testing to inform their decision-making. Digital rectal examination (DRE) by primary care clinicians has some evidence to show discrimination between benign and malignant conditions affecting the prostate. Patients referred to secondary care for diagnostic testing for prostate cancer will typically undergo a transrectal or transperineal biopsy, where a number of samples are taken and sent for histological examination. These biopsies are invasive procedures with side effects and a risk of infection and sepsis, and alternative tests such as multiparametric magnetic resonance imaging (mpMRI) are currently being trialled for their accuracy and safety in diagnosing clinically significant prostate cancer

Systemic anticancer therapies and the role of primary care

This is the author accepted manuscript. The final version is available from Wiley via the link in this recordCancer therapeutics are complex, constantly evolving, and aim to prolong the life of a patient with cancer by cure, inducing remission, or by slowing disease progression. Cancer treatments can be delivered locally directly against the tumour (i.e. surgery or radiotherapy) or systemically (i.e. chemotherapy, hormone therapy). Systemic therapies have traditionally been administered intravenously in a hospital or day unit setting; however many of the more recently discovered systemic cancer therapies are taken as an oral medication. They also pose significant potential risks to a patient’s health through side effects, immunosuppression, and later development of secondary cancers. This article focusses on systemic cancer therapies from a primary care perspective. Recent developments and classifications of systemic therapies are briefly presented. Key considerations around monitoring, potential treatment harms, and patient support are discussed to inform the delivery of primary care for cancer patients receiving systemic therapies

Exploring the causes of death among patients with metastatic prostate cancer - A changing landscape

This is the final version. Available on open access from the American Medical Association via the DOI in this recordCancer Research U

Retrospective cohort study evaluating clinical, biochemical and pharmacological prognostic factors for prostate cancer progression using primary care data

This is the final version. Available on open access from BMJ Publishing group via the DOI in this recordObjectives – To confirm the association of previously reported prognostic factors with future progression of localised prostate cancer using primary care data and identify new potential prognostic factors for further assessment in prognostic model development and validation. Design – Retrospective cohort study, employing Cox proportional hazards regression controlling for age, PSA, and Gleason score, stratified by diagnostic stage. Setting – Primary care in England Participants – Males with localised prostate cancer diagnosed between 01/01/1987 and 31/12/2016 within the Clinical Practice Research Datalink database, with linked data from the National Cancer Registration and Analysis Service and Office for National Statistics. Primary and Secondary outcomes – Primary outcome measure was prostate cancer mortality. Secondary outcomes measures were all-cause mortality and commencing systematic therapy. Up13 staging after diagnosis was not used as a secondary outcome owing to significant missing data. Results 10,901 males (mean age 74.38 +/- 9.03 years) with localised prostate cancer were followed up for a mean of 14.12 (+/- 6.36) years. 2,331 (21.38%) men underwent systemic therapy and 3,250 (31.65%) died, including 1,250 (11.47%) from prostate cancer. Factors associated with an increased risk of prostate cancer mortality included age; high PSA; current or ex-smoker; ischaemic heart disease; high C-Reactive Protein; high ferritin; low haemoglobin; high blood glucose; and low albumin. Conclusions This study identified several new potential prognostic factors for prostate cancer progression, as well as confirming some known prognostic factors, in an independent primary care data set. Further research is needed to develop and validate a prognostic model for prostate cancer progression.Can Test Collaborative/CRU

Routes to diagnosis of symptomatic cancer in sub-Saharan Africa: Systematic review

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordData availability statement: Data sharing is not applicable as no datasets are generated and/or analysed for this study. No data are available. No additional data available.Background Most cancers in sub-Saharan Africa (SSA) are diagnosed at advanced stages, with limited treatment options and poor outcomes. Part of this may be linked to various events occurring in patients' journey to diagnosis. Using the model of pathways to treatment, we examined the evidence regarding the routes to cancer diagnosis in SSA. Design and settings A systematic review of available literature was performed. Methods The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Between 30 September and 30 November 2019, seven electronic databases were searched using terms relating to SSA countries, cancer and routes to diagnosis comprising the population, exposure and outcomes, respectively. Citation lists of included studies were manually searched to identify relevant studies. Furthermore, ProQuest Dissertations Theses Global was searched to identify appropriate grey literature on the subject. Results 18 of 5083 references identified met the inclusion criteria: Eight focused on breast cancer; three focused on cervical cancer; two each focused on lymphoma, Kaposi's sarcoma and childhood cancers; and one focused on colorectal cancer. With the exception of Kaposi's sarcoma, definitive diagnoses were made in tertiary healthcare centres, including teaching and regional hospitals. The majority of participants initially consulted within primary care, although a considerable proportion first used complementary medicine before seeking conventional medical help. The quality of included studies was a major concern, but their findings provided important insight into the pathways to cancer diagnosis in the region. Conclusion The proportion of patients who initially use complementary medicine in their cancer journey may explain a fraction of advanced-stage diagnosis and poor survival of cancer in SSA. However, further research would be necessary to fully understand the exact role (or activities) of primary care and alternative care providers in patient cancer journeys.Cancer Research UK (CRUK)Can Test Collaborativ

Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients.

BACKGROUND: Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood. METHODS: A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression. RESULTS: Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain. CONCLUSIONS: Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed

Comparison of Multiparametric Magnetic Resonance Imaging and Targeted Biopsy with Systematic Biopsy Alone for the Diagnosis of Prostate Cancer: A Systematic Review and Meta-analysis

This is the final version. Available from JAMA Network via the DOI in this record. Importance: The current diagnostic pathway for patients with suspected prostate cancer (PCa) includes prostate biopsy. A large proportion of individuals who undergo biopsy have either no PCa or low-risk disease that does not require treatment. Unnecessary biopsies may potentially be avoided with prebiopsy imaging. Objective: To compare the performance of systematic transrectal ultrasonography-guided prostate biopsy vs prebiopsy biparametric or multiparametric magnetic resonance imaging (MRI) followed by targeted biopsy with or without systematic biopsy. Data Sources: MEDLINE, Embase, Cochrane, Web of Science, clinical trial registries, and reference lists of recent reviews were searched through December 2018 for randomized clinical trials using the terms "prostate cancer" and "MRI." Study Selection: Randomized clinical trials comparing diagnostic pathways including prebiopsy MRI vs systematic transrectal ultrasonography-guided biopsy in biopsy-naive men with a clinical suspicion of PCa. Data Extraction and Synthesis: Data were pooled using random-effects meta-analysis. Risk of bias was assessed using the revised Cochrane tool. Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. All review stages were conducted by 2 reviewers. Main Outcomes and Measures: Detection rate of clinically significant and insignificant PCa, number of biopsy procedures, number of biopsy cores taken, and complications. Results: Seven high-quality trials (2582 patients) were included. Compared with systematic transrectal ultrasonography-guided biopsy alone, MRI with or without targeted biopsy was associated with a 57% (95% CI, 2%-141%) improvement in the detection of clinically significant PCa, a 33% (95% CI, 23%-45%) potential reduction in the number of biopsy procedures, and a 77% (95% CI, 60%-93%) reduction in the number of cores taken per procedure. One trial showed reduced pain and bleeding adverse effects. Systematic sampling of the prostate in addition to the acquisition of targeted cores did not significantly improve the detection of clinically significant PCa compared with systematic biopsy alone. Conclusions and Relevance: In this meta-analysis, prebiopsy MRI combined with targeted biopsy vs systematic transrectal ultrasonography-guided biopsy alone was associated with improved detection of clinically significant PCa, despite substantial heterogeneity among trials. Prebiopsy MRI was associated with a reduced number of individual biopsy cores taken per procedure and with reduced adverse effects, and it potentially prevented unnecessary biopsies in some individuals. This evidence supports implementation of prebiopsy MRI into diagnostic pathways for suspected PCa.National Institute for Institute for Health Research (NIHR)Cancer Research U

A modified Delphi study to develop a practical guide for selecting patients with prostate cancer for active surveillance

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The datasets generated and/or analysed during the current study are not publicly available as consent was not sought from participants to make data publically available. Data may be available from the corresponding author on reasonable request.Background Active surveillance (AS) is a management option for men diagnosed with lower risk prostate cancer. There is wide variation in all aspects of AS internationally, from patient selection to investigations and follow-up intervals, and a lack of clear evidence on the optimal approach to AS. This study aimed to provide guidance for clinicians from an international panel of prostate cancer experts. Methods A modified Delphi approach was undertaken, utilising two rounds of online questionnaires followed by a face-to-face workshop. Participants indicated their level of agreement with statements relating to patient selection for AS via online questionnaires on a 7-point Likert scale. Factors not achieving agreement were iteratively developed between the two rounds of questionnaires. Draft statements were presented at the face-to-face workshop for discussion and consensus building. Results 12 prostate cancer experts (9 Urologists, 2 academics, 1 radiation oncologist) participated in this study from a range of geographical regions (4 USA, 4 Europe, 4 Australia). Complete agreement on statements presented to the participants was 29.4% after Round One and 69.0% after Round Two. Following robust discussions at the face-to-face workshop, agreement was reached on the remaining statements. PSA, PSA density, Multiparametric MRI, and systematic biopsy (with or without targeted biopsy) were identified as minimum diagnostic tests required upon which to select patients to recommend AS as a treatment option for prostate cancer. Patient factors and clinical parameters that identified patients appropriate to potentially receive AS were agreed. Genetic and genomic testing was not recommended for use in clinical decision-making regarding AS. Conclusions The lack of consistency in the practice of AS for men with lower risk prostate cancer between and within countries was reflected in this modified Delphi study. There are, however, areas of common practice and agreement from which clinicians practicing in the current environment can use to inform their clinical practice to achieve the best outcomes for patients

Best practice in active surveillance for men with prostate cancer: a Prostate Cancer UK consensus statement.

OBJECTIVES:To develop a consensus statement on current best practice of active surveillance (AS) in the UK, informed by patients and clinical experts. SUBJECTS AND METHODS:A consensus statement was drafted on the basis of three sources of data: systematic literature search of national and international guidelines; data arising from a Freedom of Information Act request to UK urology departments regarding their current practice of AS; and survey and interview responses from men with localized prostate cancer regarding their experiences and views of AS. The Prostate Cancer UK Expert Reference Group (ERG) on AS was then convened to discuss and refine the statement. RESULTS:Guidelines and protocols for AS varied significantly in terms of risk stratification, criteria for offering AS, and protocols for AS between and within countries. Patients and healthcare professionals identified clinical, emotional and process needs for AS to be effective. Men with prostate cancer wanted more information and psychological support at the time of discussing AS with the treating team and in the first 2 years of AS, and a named healthcare professional to discuss any questions or concerns they had. The ERG agreed 30 consensus statements regarding best practice for AS. Statements were grouped under headings: 'Inclusion/Exclusion Criteria'; 'AS follow-up protocol' and 'When to stop AS'. CONCLUSION:Significant variation currently exists in the practice of AS in the UK and internationally. Men have clear views on the level of involvement in treatment decisions and support from their treating professionals when receiving AS. The Prostate Cancer UK AS ERG has developed a set of consensus statements for best practice in AS. Evidence for best practice in AS, and the use of multiparametric magnetic resonance imaging in AS, is still evolving, and further studies are needed to determine how to optimize AS outcomes