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Ttaining chort will be recruited in the first 36 months of the study period to generate the first batch of urine metabolomic and proteomic profiles as predictive and prognostic markers.

Validation cohort will be recruited in the next 24 months of the study period .

No intervention required

Chung-Hsin Chen, MD PhD

Yeong-Shiau Pu, MD PhD

Yeong-Shiau Pu Pu, MD PhD

The study aims to identify potential urine marker metabolites as predictive or prognostic markers for treatment outcomes in patients with prostate cancer.

This is a single-center single-arm translational study where patients with prostate cancer who are about to receive definitive treatments will be invited to participate the study. After signing the approved informed consent, eligible and consenting subjects will donate their fresh urine samples for subsequent untargeted metabolomics and proteomics study to identify potential metabolite and protein markers that are able to predict responses (including efficacy and side effects) to definitive treatments. All subjects who have received varied treatment before the study can NOT be recruited.

Predictive and Prognostic Markers for Treatment Outcomes in Prostate Cancer Patients

Decipher the Biology of Lethal Prostate Cancer-Using Urine Metabolomics and Proteomics Profiling to Search for Predictive and Prognostic Markers for Treatment Outcomes in Prostate Cancer Patients

National Taiwan University Hospital

Symptoms and General Pathology

Recurrence

Disease Attributes

Katharine C Webb, BSc MBBS MSc

Andrea Sottoriva, BSc MSc PhD

Julia Murray, PhD FRCR

Alison Reid, BSc MRCP

Prostate cancer is the most common cancer in males in the UK, and current estimates are that 1 in 8 will be diagnosed with prostate cancer in their lifetime. Although surgery or radiotherapy with hormone therapy offers a good chance of cure in localised disease, recurrence can occur, which may cause significant distress, and may shorten the patient's life. In patients with locally advanced disease (disease that has broken through the surrounding capsule of the prostate gland), around 30-40% of patients experience a recurrence.

Cancer develops as a result of normal cells acquiring genetic mutations, and localised prostate cancer at diagnosis is commonly made up of different subclones - distinct regions within the patient's cancer with different sets of genetic mutations, each of which may behave differently and be more or less sensitive to treatments.

The IMRT clinical trial (CCR 1766) recruited 486 patients who received hormone therapy and radiotherapy to the prostate and lymph nodes in patients with locally advanced prostate cancer. The FORECAST study (FORecasting the Evolution of CAncer of the proState within a Trial) is undertaking genetic sequencing of several regions of these patients' prostate cancers in order to determine which subclones are present at diagnosis, and how they evolved. FORECAST also has permission to obtain and perform sequencing on primary samples from two other large trials in localized prostate cancer.

This study seeks to collect blood samples from patients who have experienced a recurrence in whom the primary biopsies have been sequenced as part of FORECAST. Additionally, blood will be collected from any patient in follow up at The Royal Marsden who received radiotherapy and hormone therapy for a localised prostate cancer and has experienced a recurrence but not yet started treatment. In these patients, the FORECAST protocol will be used to undertake genetic sequencing of their original prostate cancer biopsies. Genetic mutations from the cancer can be detected in the blood in patients who relapse, so-called 'liquid biopsies'. By comparing the genetic information between the primary and relapsed cancer, we can detect which subclones present at diagnosis are ultimately responsible for the cancer relapsing, and help us to understand the evolution of prostate cancers over time. This will assist us in predicting at the point of diagnosis which patients are more likely to relapse, so that we may consider escalating primary treatments or treating patients with high-risk subclonal mutations with targeted therapies upfront. As a result, we aim to reduce the number of patients treated for localised prostate cancer experiencing a recurrence. Additionally, although liquid biopsies are well-characterized in metastatic prostate cancer, little is known about their value in patients who have a biochemical-only relapse (patients who have a rising PSA with no evidence of cancer on scans) and this will also be explored.

Blood sample(s) to be collected from patients and then stored under unique trial identifier in the Principal Investigator's laboratory at the Institute of Cancer Research. Samples to be collected for DNA extraction, library prep, sequencing, and bioinformatic analysis. Remaining biological material to be sent to ICR Biobank.

Exploring the Mechanisms and Dynamics of Clonal Evolution Leading to Recurrence in Prostate Cancer

Exploring the Mechanisms and Dynamics of Clonal Evolution Leading to Recurrence in Prostate Cancer Through Evaluation of Intratumour Heterogeneity at Diagnosis and Circulating Tumour DNA at Recurrence

Fully anonymised DNA sequencing data will be stored in an online repository such as the European Genome- Phenome Archive at the European Bioinformatics Institute, or the forthcoming ICR (Institute of Cancer Research) repository. The data will be encrypted and accessible only to us unless a potential collaborator enters into an agreement with our group at the ICR and we agree to share the data as part of an ethically-approved study. No patient-identifiable information will be shared.

This is a basic science/ translational study and therefore no strict pre-determined primary outcome can be defined as it is hypothesis-generating. This study aims to identify prognostic evolutionary or genetic biomarkers in localised prostate cancers and such biomarkers can then be evaluated further in clinical studies.

Royal Marsden NHS Foundation Trust

Institute of Cancer Research, United Kingdom

Patients who received 78Gy RT to the prostate gland 3-4.5 years prior to enrollment. This group will not be receiving any active treatment

Patients in this group will receive one of 2 treatment arms of their choice:

* Arm 1: VMAT delivery with integrated VMAT boost (IB-VMAT) GTV: 95Gy in 38fractions
* Arm 2: HDR-boost followed by VMAT GTV: 10Gy HDR + 76Gy in 38 fractions VMAT

Volumetric Modulated Arc Therapy (VMAT) and High-Dose Rate (HDR) Radiotherapy

Already had prior radiation treatment. MRI-guided prostate biopsy at 3 years and PSA per standard practice

No Active Treatment - completed Prior Radiation

Peter Chung, MB ChB

Prostate cancer is common in males and may develop over the course of an individual's life. This cancer is often discovered at the time of routine physical examinations and/or blood work or on rectal examination. Once diagnosed, most patients do require some form of treatment so that the prostate cancer does not progress to cause damage and/or shortened lifespan. Occasionally, after patients receive treatment, the investigators have found that an area of cancer remains within the prostate. Those patients with a large area of cancer (i.e. seen on MRI image) appear to have a higher chance of remaining or recurrent prostate cancer even after standard treatment. Thus, the investigators believe that the area of the prostate gland occupied by a dense area of cancer may need more radiation therapy than normal to remain cancer free.

Standard therapy currently in place in North America: Currently patients who are diagnosed with prostate cancer have 3 common options: surgery, external beam radiation therapy (EBRT) alone or internal radiation (brachytherapy). Patients may or may not receive hormone therapy alongside the radiation depending on their physician's preference. For those who receive radiation therapy, the tumor typically receives the same dose as the rest of the prostate gland.

Findings to date: In the past few years the investigators have discovered that patients with a tumor large enough to be seen on MRI images (\>5mm) have a higher chance than normal of having cancer remain in the prostate, despite receiving treatment for their cancer 3 years earlier. Using new technology investigators can deliver radiation therapy after viewing the prostate tumor on MRI. This guides therapy, allowing the radiation treatment to be targeted to the tumor within the prostate. Based on this earlier success the investigators believe that they can now safely give a higher dose of radiation to specifically target the cancer within the prostate gland.

Reason for the study: The investigators would like to test this technology and expertise to give radiation to a higher than normal dose to the tumor nodule in prostate gland.

This is a prospective two arm phase 2 trial investigating the technical and clinical performance of tumor-targeted (rather than prostate targeted) radiotherapy.

Cohort 1 (Control group): This group consists of patients who have had previous radiation. This group will not receive any active treatment but will have a biopsy at 3 years from the time they completed their radiation therapy. Patient in this group will also continue to have their PSA checked per standard practice

Cohort 2 (Experimental group): Patients in this group will receive one of 2 treatment arms of their choice. In addition to the MRI-guided prostate biopsy at 3 years and regular standard of care PSA checks, this group will also complete a quality of life questionnaire and have regular imaging per standard practice.

Both groups will be followed by the research team per protocol.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Predictive and Prognostic Markers for Treatment Outcomes in Prostate Cancer Patients	NCT03237026	Prostate Cancer	No intervention...	30 Years - 100 Years	National Taiwan University Hospital
Exploring the Mechanisms and Dynamics of Clonal Evolution Leading to Recurrence in Prostate Cancer	NCT04686188	Prostate Cancer...		18 Years -	Institute of Cancer Research, United Kingdom
Tumor TARGET Prostate Cancer	NCT01802242	Prostate Cancer	Volumetric Modu... No Active Treat...	18 Years -	University Health Network, Toronto

Spots Global Cancer Trial Database for prostate radiotherapy