Prostate adenocarcinoma definitive EBRT conventional low-risk

• Intact prostate.

• Low-risk prostate adenocarcinoma. See prostate adenocarcinoma risk category features table.

• ECOG 0-2.

• Life expectancy >10 years.

Cautions

• Previous high dose radiation to the pelvis.

• Poor urinary and bowel function.

• Radiosensitising medications (e.g. methotrexate).

• Inflammatory bowel disease and/or history of adhesions/bowel obstruction.

• Bilateral hip replacement.

• Non-rheumatoid collagen vascular disorders.

• Cardiac implantable electronic devices (CIEDs).

Indications notes

• Active surveillance should be offered in all men in the low-risk prostate cancer group.

• Hypofractionated radiation therapy should be offered to patients with low-risk prostate cancer. See ID 3370 - Prostate adenocarcinoma definitive EBRT hypofractionation.

• If the patient has recently undergone a transurethral resection of the prostate (TURP) wait 8-12 weeks until urinary function has stabilised, before commencing radiation therapy.

• If inserting fiducial markers, ensure insertion is more than 5 days prior to planning CT.

• Optional use of hydrogel spacer.^r

Androgen deprivation therapy (ADT)

• The use of androgen deprivation therapy (ADT) is not recommended for patients in the low-risk group.

Prescription notes

• Hypofractionated radiation therapy should be offered to low, intermediate, and select high-risk patients. See ID 3370 - Prostate adenocarcinoma definitive EBRT hypofractionation.

• If delivering doses less than 73.8 Gy EQD2, neoadjuvant or adjuvant hormone therapy is recommended to compensate for the lower radiation dose.

Margin ranges have been agreed by the Radiation Oncology reference committee and reflect safe clinical practice.

Target volume guides

• FROGG consensus guidelines for definitive EBRT in prostate adenocarcinoma.^r

• Radiographic and anatomic basis for prostate contouring errors and methods to improve prostate contouring accuracy.^r

• ESTRO ACROP consensus guidelines of localised prostate cancer.^r

Target verification recommendations reflect the minimum imaging required for the safe delivery of this protocol.

Efficacy

There are no randomised controlled trials to demonstrate a superiority of one treatment modality over the other in low-risk prostate cancer.

The key evidence supporting this protocol comes from: a meta-­analysis by Viani et al. of 7 randomised controlled trials, including 2812 patients investigating dose escalation (greater than 70 Gy); the MRC­RT01 and MD Anderson RCTs; and the RTOG 94.06 Michalski study.^rrrrrr

Dose escalation

Dose escalation (greater than 74 Gy) for patients with low-risk prostate cancer has previously shown limited benefit in this setting.

Viani et al. found a significant reduction in the incidence of biochemical failure in patients with low, intermediate and high-risk localised prostate cancer; 24.8% with high dose radiation therapy versus 34.6% with conventional dose radiation therapy (p <0.0001).^r On subgroup analysis, all subgroups showed a linear correlation between total dose of radiation therapy and biochemical failure. The subgroup analyses of 4 RCTs and 602 low-risk patients, showed high dose radiation therapy reduces the relative risk of biochemical failure by approximately 50%, however, no difference in mortality rate and prostate cancer-specific mortality rates between high dose and conventional dose radiation therapy was demonstrated.^r

Figure 2. Meta-analysis regarding biochemical failure for all subgroups

© Int J Radiat Oncol Biol Phys 2009^r

The MDACC phase III RCT compared 70 Gy to 78 Gy EBRT. At 8 years post-radiation, patients with low­-risk disease in the 78 Gy group had a freedom from failure (clinical and/or biochemical) of 88% compared to the 70 Gy group who had a freedom from failure rate of 63% (p = 0.042). No dose related effect on freedom from failure was found for favourable patients with a pre-treatment PSA <10 ng/ml.^r

© Int J Radiat Oncol Biol Phys 2008^r

To date, no randomised trial has documented a survival benefit attributable to higher radiation doses. The RTOG 94.06 phase II trial (1084 patients randomised across 5 dose levels) also confirmed dose escalation yields favourable outcomes for localised prostate cancer.^r

© Int J Radiat Oncol Biol Phys 2012^r

Hypofractionation

Hypofractionation is recommended for prostate only radiation therapy. Long-term outcomes and toxicity are comparable to conventional fractionation.^rr Evidence supporting moderate hypofractionation for low-risk prostate cancer is not discussed within this protocol, but can be found in the evidence and efficacy sections of ID 3370 Prostate adenocarcinoma definitive EBRT hypofractionation.

Toxicity

A summary of the most clinically significant toxicities associated with this protocol are included in the table below: