A Prospective Phase II Dose Escalation Study Using IMRT for High Risk N0 M0 Prostate Cancer. ICORG 08-17

This is a prospective, phase II non-randomised controlled clinical study. Dose escalation will be implemented using 1.8 Gy increments from baseline 75.6 Gy. Patients' RT prescription may be escalated up to max 81 Gy once dose volume constraints are adhered to. All patients will be treated using the participating institution's standard rectal preparation protocol, bladder-filling protocol and appropriate immobilisation device(s). Cone beam CT on-treatment imaging is recommended for this study. However, the use of individual institutional imaging equipment and techniques is permitted. Acute GU/GI toxicities will be assessed weekly during treatment. GU/GI toxicities will also be assessed 2 months post RT, 8 months post RT and 6 monthly thereafter to year nine and in line with the participating institution's standard routine follow-up (FU) thereafter. Translational sub-studies (optional), only apply to patients who are consented prior to commencement of hormone therapy at centres participating in the translational sub-study. Patients at centres participating in the translational sub-studies will be given the option of participating in sub-study 1 (Proteomic Analysis), sub-study 2 (Raman spectroscopic analysis), or both (sample collection will not be mandatory).

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

1. Patients undergoing a radical course of RT for high-risk disease (defined according to the National Comprehensive Cancer Network Practice Guidelines in Oncology v.1 as one or more of the NCCN high risk criteria \> or equal to T3, \> or equal to Gleason 8, PSA \> 20ng/ml)
2. Only patients requiring neo-adjuvant / adjuvant hormonal therapy will be included in this study
3. Absence of distant metastases as demonstrated by history and physical examination, FBC, screening profile including liver function tests, PSA and bone scan
4. All patients must have an MRI/CT of the prostate and pelvis to investigate the nodal status and precise T-stage. This MRI/CT scan must be performed prior to commencement of hormonal therapy. Suspicious nodes need to be histologically proven to be benign before the patient can be included in the study). M0 on staging.
5. No previous surgery for urinary conditions except TURP or TRUS
6. KPS \> or equal to 60
7. Age \>18 years
8. Provision of written informed consent in line with ICH-GCP guidelines

Exclusion Criteria:

1. Previous RT to the pelvic region
2. The patient has nodal involvement or it is decided to electively treat pelvic lymph nodes
3. The patient has had a bilateral orchidectomy
4. The patient has previously received a full course of hormonal treatment for his prostate cancer
5. The patient has or has had other malignancies within the last 5 years (non-melanoma skin cancer is permitted)
6. Evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the trial or if it is felt by the research/ medical team that the patient may not be able to comply with the protocol
7. Patients who have had a prostatectomy
8. The presence of hip prostheses

• BACKGROUNDMedipally DK, Maguire A, Bryant J, Armstrong J, Dunne M, Finn M, Lyng FM, Meade AD. Development of a high throughput (HT) Raman spectroscopy method for rapid screening of liquid blood plasma from prostate cancer patients. Analyst. 2017 Apr 10;142(8):1216-1226. doi: 10.1039/c6an02100j. PMID 28001146
• BACKGROUNDMedipally DKR, Nguyen TNQ, Bryant J, Untereiner V, Sockalingum GD, Cullen D, Noone E, Bradshaw S, Finn M, Dunne M, Shannon AM, Armstrong J, Lyng FM, Meade AD. Monitoring Radiotherapeutic Response in Prostate Cancer Patients Using High Throughput FTIR Spectroscopy of Liquid Biopsies. Cancers (Basel). 2019 Jul 2;11(7):925. doi: 10.3390/cancers11070925. PMID 31269684
• BACKGROUNDCagney DN, Dunne M, O'Shea C, Finn M, Noone E, Sheehan M, McDonagh L, O'Sullivan L, Thirion P, Armstrong J. Heterogeneity in high-risk prostate cancer treated with high-dose radiation therapy and androgen deprivation therapy. BMC Urol. 2017 Aug 1;17(1):60. doi: 10.1186/s12894-017-0250-2. PMID 28764689
• DERIVEDMeade AD, Maguire A, Bryant J, Cullen D, Medipally D, White L, McClean B, Shields L, Armstrong J, Dunne M, Noone E, Bradshaw S, Finn M, Shannon AM, Howe O, Lyng FM. Prediction of DNA damage and G2 chromosomal radio-sensitivity ex vivo in peripheral blood mononuclear cells with label-free Raman micro-spectroscopy. Int J Radiat Biol. 2019 Jan;95(1):44-53. doi: 10.1080/09553002.2018.1451006. Epub 2018 Mar 29. PMID 29528761