Prostate cancer is the most commonly diagnosed cancer among Canadian men, and is the third leading cause of cancer-related death. In Canada, there will be an estimated 24,600 new cases of prostate cancer diagnosed, representing 20% of all new cancers in men. On average 67 Canadian men will be diagnosed with, and 13 Canadian men will die from prostate cancer every day. This represents 10% of all cancer deaths in men in 2022. 1 Guideline Questions 1. How should patients with localized prostate cancer be risk stratified? 2. How should patients with localized prostate cancer be managed? 3. How should patients with localized prostate cancer be followed after they have completed treatment?

# Search Strategy
For the most recent version of the guideline, the PubMed database was searched using the following criteria: (local[

# Target Population
Adult men (18 years of age or older) with a suspicion or recent diagnosis of localized prostate cancer.
For a complete list of early detection and screening recommendations please refer to the 2022 Canadian Urological Association recommendations (link  7 o Patients with pubic arch interference may not be eligible for brachytherapy. o Patients with borderline pubic arch interference may be considered for a short course of ADT to reduce gland size. o Patients with a prior transurethral resection (TURP) should be assessed on an individual basis. o Patients with significant baseline obstructive symptoms may not be eligible for brachytherapy (i.e. American Urological Association symptom score >20).  External beam radiotherapy: 8 o Intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) should be used for delivery o Hypofractionated radiation may be considered. 9 o Daily image guidance is the standard of care. o The clinical target volume (CTV) is defined as the prostate alone.  Whole gland cryosurgery is an alternative therapeutic option for patients who may not be good candidates for surgery or radiation. There is less long-term data regarding efficacy and toxicity compared to the other treatment modalities. 10  Whole gland high intensity focused ultrasound (HIFU) is not a recommended treatment option for low-risk disease. 11 7. Follow-up for Low-Risk Disease:  PSA every 6 to 12 months for 5 years, then yearly.  Evaluation of treatment morbidity and/or complications.

# Management of Intermediate-Risk Disease
- Treatment Options for Intermediate Risk Disease: 12  Radical prostatectomy plus bilateral pelvic lymph node dissection. 13  External beam radiotherapy 3,14,15 o Intensity modulated radiation therapy (IMRT) or volumetric modulated arc therapy (VMAT) should be used for delivery o Hypofractionated radiation and SBRT may be considered. 9, o Short term (neoadjuvant + concurrent, 4-6 months total) ADT may be considered for select patients undergoing radiotherapy. 19, 20 o The CTV is defined as the prostate +/-seminal vesicles.  Low-dose rate (LDR) Brachytherapy  EBRT with a brachytherapy boost (+/-ADT) is an option for patients with high-tier intermediate risk disease. 8,21,22 o Brachytherapy may be delivered as either LDR or high dose rate (HDR). 8,21,22 o Short term (neoadjuvant + concurrent, 4-6 months total) ADT may be considered for select patients undergoing brachytherapy. 18,19  Active surveillance may be considered for selected patients with low-tier intermediate risk prostate cancer.  Whole gland cryosurgery is an alternative therapeutic option for patients who may not be good candidates for surgery or radiation. There is less long-term data regarding efficacy and toxicity compared to the other treatment modalities. 23  Whole gland high intensity focused ultrasound (HIFU) is not a recommended treatment option for intermediate-risk disease. 11  Focal therapy may be considered for selected patients in the context of a clinical trial 9. Follow-up for Intermediate-Risk Disease:
- PSA every 6 to 12 months for the first 5 years, then yearly.  Evaluation of treatment morbidity and/or complications.

# Management of High-Risk Disease
All high-risk disease patients should be encouraged to discuss treatment options with both a Urologist and Radiation Oncologist before starting treatment.
- Treatment Options for High-Risk Disease: 12  EBRT + ADT.  o There is growing evidence for hypofractionation in this patient group. 28 o The CTV is defined as the prostate + seminal vesicles +/-regional lymph nodes. o EBRT with a brachytherapy boost (+/-ADT for 12 months) is an option for patients with high risk disease. 8,21,22 o ADT should be administered for an 18 -36 month duration and may be initiated prior to radiotherapy or concurrently with EBRT. 27 o An anti-androgen could be co-administered with a LHRH agonist and be continued for at least 7 days (for possible flare in testosterone with initial LHRH agonist alone). o Patients may be considered for the addition of abiraterone plus prednisolone to LHRH agonist o Refer to the clinical practice guideline on Bone Health for Prostate Cancer for recommendations regarding bone health for patients on ADT.  Radical Prostatectomy and Pelvic Lymphadenectomy should be considered only for patients with resectable disease where the intent is to achieve negative margins. Patients should be counselled that there is a significant likelihood of requiring multimodality therapy with post-operative radiotherapy and ADT.  Whole gland cryosurgery is an alternative therapeutic option for patients who may not be good candidates for surgery or radiation. There is less long-term data regarding efficacy and toxicity compared to the other treatment modalities. 23,29 11. Follow-up for High-Risk Disease  First post-operative PSA should be done 4-12 weeks after surgery.  Routine PSA should be done every 6 months, unless otherwise specified.
- Post-prostatectomy Treatment Options  Early salvage radiation therapy is the preferred strategy over adjuvant radiation therapy (i.e., positive margins, pT3), and should be considered at the time of biochemical failure (PSA 0.2 ng/mL on at least 2 readings). 30-33  ADT can be considered with post-operative radiation therapy in select high-risk patients; the optimal type and duration of ADT has not been established. 34,35  The CTV is the prostate bed; addition of pelvic lymph node regions may be considered in select high-risk patients.   The total dose to the prostate bed should be at least 66Gy in standard fractionation. 13. ADT alone is an alternative therapeutic option for patients who decline or are not eligible for curative local treatment. 24 Refer to the clinical practice guideline on Bone Health for Prostate Cancer for recommendations regarding bone health for patients on ADT.

# Biochemical Recurrence Following Local Radical Radiation Therapy
- The definition of a biochemical recurrence is PSA nadir +2 ng/mL after primary radiation therapy, or any rise in PSA after salvage RT.
- Investigations to rule out metastatic disease include a bone scan and a CT scan. For postradiotherapy patients, a repeat prostate biopsy is recommended to confirm local recurrence if local salvage therapy is being considered.
- Recommended options for salvage local therapy include salvage cryosurgery or salvage brachytherapy. If salvage local therapy is not offered, or if the patient fails salvage local therapy, initiation of ADT is indicated.  Intermittent therapy is not inferior to continuous therapy. 39  There is no absolute PSA threshold for initiating ADT, but a range of 5-10 is reasonable 40 ; and consideration should also be given to PSA doubling time.

# Development and Revision History
This guideline was developed by a multidisciplinary working group comprised of members from the Alberta Provincial GU Tumour Team, external participants identified by the Working Group Lead, and a methodologist from the Guideline Resource Unit. The draft guideline was externally reviewed and endorsed by members of the Alberta Provincial GU Tumour Team who were not involved in the guideline's development, including urologists, radiation oncologists, medical oncologists, nurses, pathologists, and pharmacists. A detailed description of the methodology followed during the guideline development process can be found in theGuideline Resource Unit Handbook.
This guideline was originally developed in January 2017, and was updated in January 2018, March 2020, November 2020, and December 2022.
A formal review of the guideline will be conducted in 2023. If critical new evidence is brought forward before that time, however, the guideline working group members will revise and update the document accordingly.
ADT, androgen deprivation therapy; CT, computed tomography scan; CTV, clinical target volume; DRE, digital rectal exam; EBRT, eternal beam radiotherapy; HDR, high dose rate; HIFU, high intensity focused ultrasound; ICRU, international commission on radiation units; IMRT, intensity modulated radiotherapy; LDR, low dose rate; LHRH, luteinizing hormonereleasing hormone; MRI, magnetic resonance imaging; PSA, prostate specific antigen; TURP, transurethral resection