Two-fraction HDR Monotherapy for Localized Prostate Cancer

This is a single center single arm prospective pilot study investigating the safety of high dose rate (HDR) brachytherapy as monotherapy delivered in 2 fractions 3 hours apart. HDR monotherapy has been established as safe and effective in this context, however previous studies have delivered 2 fractions on separate days, or at least 6 hours apart. Clinically, this regimen, if shown to be safe and effective in future studies, has the potential to reduce operative resources and logistical stresses on brachytherapy departments.

Sex

Male

Minimum age

18 Years

Inclusion Criteria:

1. Participants must have histologically or cytologically confirmed diagnosis of prostate adenocarcinoma.
2. National Comprehensive Cancer Network favorable intermediate risk stratification, defined as one or more intermediate risk factors such as cT2b - cT2c category, grade group 1 or 2, or PSA 10-20 ng/mL, and less than 50% of biopsy cores positive for carcinoma (i.e. for this trial, we will only include systematic biopsy cores, not targeted biopsy cores).
3. Age \>=18 years.
4. Eastern Cooperative Oncology Group (ECOG) performance status \<2 (Karnofsky \>60%).
5. Eligible to undergo High dose rate (HDR) brachytherapy as monotherapy as determined by the treating radiation oncologist.
6. Ability to understand and the willingness to sign a written informed consent document.
7. Human immunodeficiency virus (HIV)-infected individuals on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
8. For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated.
9. Individuals with a history of hepatitis C virus (HCV) infection must have been treated and cured. For individuals with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.
10. Individuals with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
11. Willingness and ability to complete International Prostate Symptom Score questionnaires.

Exclusion Criteria:

1. Any prior treatment for prostate cancer.
2. Prior history of pelvic malignancy.
3. Any prior androgen deprivation therapy.
4. Is currently receiving any other investigational agents.
5. Abnormal pre-brachytherapy assessment raising concern for undergoing HDR brachytherapy procedure.
6. Contraindications to general anesthesia.
7. Contraindications to radiotherapy.
8. Prior history of pelvic radiotherapy.
9. Presence of lymph node or distant metastases.
10. Prior cryosurgery or cryotherapy to the prostate.
11. Prior transurethral resection of the prostate (TURP) or transurethral incision within the previous 6 months.
12. Estimated prostate volume \>60 cubic centimeters as determined by transrectal ultrasound or magnetic resonance imaging.
13. IPSS score of 15 or higher prior to treatment.

• BACKGROUNDMartell K, Mendez LC, Chung HT, Tseng CL, Alayed Y, Cheung P, Liu S, Vesprini D, Chu W, Wronski M, Szumacher E, Ravi A, Loblaw A, Morton G. Results of 15 Gy HDR-BT boost plus EBRT in intermediate-risk prostate cancer: Analysis of over 500 patients. Radiother Oncol. 2019 Dec;141:149-155. doi: 10.1016/j.radonc.2019.08.017. Epub 2019 Sep 12. PMID 31522882
• BACKGROUNDViani GA, Arruda CV, Assis Pellizzon AC, De Fendi LI. HDR brachytherapy as monotherapy for prostate cancer: A systematic review with meta-analysis. Brachytherapy. 2021 Mar-Apr;20(2):307-314. doi: 10.1016/j.brachy.2020.10.009. Epub 2021 Jan 15. PMID 33461894
• BACKGROUNDMorton G, McGuffin M, Chung HT, Tseng CL, Helou J, Ravi A, Cheung P, Szumacher E, Liu S, Chu W, Zhang L, Mamedov A, Loblaw A. Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy. Radiother Oncol. 2020 May;146:90-96. doi: 10.1016/j.radonc.2020.02.009. Epub 2020 Mar 5. PMID 32146259
• BACKGROUNDAlayed Y, Loblaw A, McGuffin M, Chung HT, Tseng CL, D'Alimonte L, Cheung P, Liu S, Chu W, Szumacher E, Helou J, Ravi A, Haider M, Mamedov A, Zhang L, Morton G. Single-fraction HDR brachytherapy as monotherapy in low and intermediate risk prostate cancer: Outcomes from two clinical trials with and without an MRI-guided boost. Radiother Oncol. 2021 Jan;154:29-35. doi: 10.1016/j.radonc.2020.09.007. Epub 2020 Sep 10. PMID 32918971
• BACKGROUNDCorkum MT, Achard V, Morton G, Zilli T. Ultrahypofractionated Radiotherapy for Localised Prostate Cancer: How Far Can We Go? Clin Oncol (R Coll Radiol). 2022 May;34(5):340-349. doi: 10.1016/j.clon.2021.12.006. Epub 2021 Dec 25. PMID 34961659
• BACKGROUNDKukielka AM, Dabrowski T, Walasek T, Olchawa A, Kudzia R, Dybek D. High-dose-rate brachytherapy as a monotherapy for prostate cancer--Single-institution results of the extreme fractionation regimen. Brachytherapy. 2015 May-Jun;14(3):359-65. doi: 10.1016/j.brachy.2015.01.004. Epub 2015 Feb 28.