Title: Multimodal treatment for patients with prostate cancer: a national study using existing electronic data.
Funder: Department of Health and Social Care

Abstract: Background:Prostate cancer is the most frequently diagnosed solid cancer in men in the UK. This accounts for over 46,000 new diagnoses and over 11,000 deaths annually. One third of men with newly diagnosed prostate cancer have locally-advanced disease and between 10% and 40% of these men die within 5 years. Locally-advanced prostate cancer poses a significant treatment challenge in order to gain both local control and treat any microscopic metastases. For this reason, multimodal treatment layers multiple therapies to improve survival.Combining hormones with radiotherapy is well established for men with locally-advanced prostate cancer, but uncertainty surrounds the use of pelvic lymph node irradiation. Brachytherapy and chemotherapy, combined with radiotherapy, are also rapidly developing a role for these men. In selected cases, initial radical prostatectomy can be used within the multimodal setting, as adjuvant radiotherapy has shown to improve relapse-free survival in men with high-risk features (positive margins, capsule rupture and/or seminal vesicle involvement).The strategy of multimodal treatment is endorsed by international guidelines but treatment selection and timing is hotly debated. The current management of men with locally-advanced prostate cancer needs to be assessed and the toxicity of multimodal treatment reviewed nationally.Aim:To use linked longitudinal electronic healthcare data to assess the use of multimodal treatment for men with locally-advanced prostate cancer and assess its toxicity.Research Questions:1. How are men with locally-advanced prostate cancer currently managed in England, and what are the factors associated with treatment selection? 2. Does pelvic radiotherapy to regional lymph nodes, in addition to prostate-only radiotherapy, affect medium-term outcomes in men receiving primary radiotherapy for their prostate cancer? 3. Does the timing of post-prostatectomy radiotherapy affect medium-term outcomes in men with prostate cancer? 4. Does brachytherapy boost, in addition to primary radiotherapy, affect medium-term outcomes in men with prostate cancer?Analysis Plan:I will use a linked national dataset of the National Cancer Registry Data (NCRD) and the National Prostate Cancer Audit (NPCA) database to identify my population of men with prostate cancer. Treatment information will be derived from the Hospital Episode Statistics (HES), the National Radiotherapy Dataset (RTDS) and the Systematic Anti-Cancer Therapy (SACT) database.The NPCA, HES and the NPCA organisational survey will be used to determine demographic, patient and organisational factors associated with treatment selection (Question 1). Severe medium-term complications will be measured using validated performance indicators to identify diagnosis and procedure codes in HES. NPCA patient-reported outcome measures (PROMs) will be used to quantify functional outcomes 18 months after diagnosis. Mortality will be measured using three year survival data in HES. I will look at how toxicity and cancer mortality changes with a multimodal approach (Questions 2, 3 and 4).NHS Services, Patients and Public:My research will immediately provide measures of treatment toxicity which will guide treatment decisions for patients with locally-advanced cancer. My research findings on the factors associated with treatment selection will support NHS services to make improvements in the equity of access to multimodal treatment.

Lay abstract: Background:Prostate cancer is the most common non-skin cancer in men in the UK. It accounts for over 46,000 new cancers and is the cause of approximately 11,000 deaths annually. This makes prostate cancer the second largest cause of death from cancer in the UK. When initially diagnosed, approximately one third of cases are locally-advanced as they have already spread outside the prostate gland or into lymph nodes in the pelvis. When the cancer is no longer contained within the prostate there is a poor outcome with between 10% and 40% of patients dying within 5 years.Intensive treatment is vital in order to treat the cancer within the prostate and the cells which have spread. This is why a number of treatments are combined to give the best chance of a cure. Particularly aggressive tumours, which initially appear to be contained within the prostate, have a high chance of having unnoticed cancer cells within the pelvis and are therefore treated in the same way as locally-advanced cancers. The treatments include combinations of surgery, radiotherapy, brachytherapy, chemotherapy and hormones. Brachytherapy is a type of internal radiotherapy that can be used in combination with conventional radiotherapy. International guidelines endorse the use of multiple treatments but we need to know more about the impact of the side effects that men experience with these treatment combinations, such as problems with erections, problems passing urine and bowel problems.Project Aim:To investigate how men with locally-advanced prostate cancer are currently treated and how the use of multiple treatments alters the side effects that men experience.Research Questions:1. How are men with locally-advanced prostate cancer currently managed in England and which factors determine the treatments used? 2. Does radiotherapy to the pelvic lymph nodes, in combination with radiotherapy to the prostate, have an impact on the side effects that men normally experience from radiotherapy to the prostate alone? 3. Does the timing of radiotherapy following surgery (immediate or delayed) impact on the side effects that men experience from both treatments? 4. Does brachytherapy, in combination with radiotherapy, change the side effects that men experience from radiotherapy alone?Design and Methods:I will use five linked national databases to obtain information about the treatments that men receive and the side effects they experience. The databases will contain information on prostate cancer characteristics, hospital operations/procedures, radiotherapy and chemotherapy. Different side effects will be measured using patient surveys and hospital data. Statistical analysis will be used to compare different treatment groups to see if any differences exist. Benefit to Patients and the Public:This work will highlight any specific patient groups who appear more likely to miss out on multiple treatments for their prostate cancer and whether hospital or geographical variation alters treatment selection. Any treatment inequality found will encourage healthcare providers to change their practice and improve treatment availability. Knowledge of the side effects of different treatment combinations is important for patients so that they can make informed decisions about their care.Patient and Public InvolvementA Clinical Reference Group (CRG) for the National Prostate Cancer Audit (NPCA) has been involved continuously with the development of ongoing research and amalgamates the expertise of clinicians, commissioners and patients. Its patient representation, from Prostate Cancer UK and Tackle Prostate Cancer, has ensured that this project is relevant to patients and that their input will be implemented throughout.Dissemination of FindingsMy findings will be communicated to the CRG and its patient representatives. I will also present my research at national and international conferences, and publish in relevant peer reviewed journals to achieve international dissemination.

Research activity codes: 6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS