What are the recommended radiotherapy guidelines for localized prostate cancer?

Radiotherapy Guidelines for Localized Prostate Cancer

Fractionation Approach by Risk Category

Moderate hypofractionation (240-340 cGy per fraction) should be offered to all patients with localized prostate cancer across all risk categories, as it provides equivalent cancer control and toxicity compared to conventional fractionation with significant advantages in treatment duration and convenience. 1, 2

Low-Risk Disease

• Moderate hypofractionation (e.g., 60 Gy in 20 fractions over 4 weeks) is strongly recommended based on high-quality randomized trial evidence demonstrating non-inferiority to conventional fractionation (74 Gy in 37 fractions) with 5-year biochemical-clinical failure-free survival of 90.6% 3, 1
• Ultrahypofractionation (≥500 cGy per fraction) may be conditionally offered as an alternative for patients who decline active surveillance, though enrollment in clinical trials or registries is encouraged 1, 2
• No androgen deprivation therapy (ADT) should be added for low-risk patients receiving radiation 2, 4
• Pelvic lymph node irradiation should not be performed in low-risk patients, as prospective trials showed no benefit (adjusted HR 0.96,95% CI 0.64-1.43) 1

Intermediate-Risk Disease

Favorable Intermediate-Risk

• Moderate hypofractionation alone (without ADT) is appropriate, using doses of 60 Gy in 20 fractions or equivalent 1, 2
• Pelvic lymph node irradiation should not be performed, as RTOG 9413 demonstrated no significant difference in biochemical failure rates 1

Unfavorable Intermediate-Risk

• Moderate hypofractionation with 4-6 months of ADT is strongly recommended, as multiple randomized trials demonstrated consistent oncologic benefit with the addition of ADT (HR 0.83 for metastasis-free survival, 95% CI 0.77-0.89, p<0.0001) 1
• The Panel acknowledges that 4-month ADT courses are commonly used to mitigate deleterious ADT effects while maintaining cancer control benefits, though 6-month courses have more robust evidence 1
• Pelvic lymph node irradiation should not be routinely performed 1

High-Risk Disease

High-risk patients should receive external beam radiation therapy (EBRT) using intensity-modulated radiation therapy (IMRT) techniques with doses of 78-80+ Gy combined with long-term ADT (24-36 months). 4, 1

• Moderate hypofractionation may be offered for high-risk disease, though the evidence quality is lower (Grade C) compared to other risk categories 1, 2
• Ultrahypofractionation should not be offered outside of clinical trials or multi-institutional registries due to insufficient comparative evidence 1, 2
• Long-term ADT (24-36 months) is mandatory, as the EORTC trial demonstrated improved 5-year overall survival with 36 months versus 6 months (84.8% vs 81.0%, HR 1.42; 95% CI 1.09-1.85) 4, 1
• Pelvic lymph node irradiation should be considered for high-risk patients 4, 1
• Combination EBRT plus brachytherapy (trimodality with ADT) should be considered, as analysis of 12,745 high-risk patients showed reduced disease-specific mortality compared to EBRT alone (HR 0.77; 95% CI 0.66-0.90) 4

Dose Specifications

Moderate Hypofractionation Regimens

• 60 Gy in 20 fractions over 4 weeks is the most validated regimen, demonstrating non-inferiority with HR 0.84 (90% CI 0.68-1.03) and 5-year biochemical-clinical failure-free survival of 90.6% 3, 1
• 57 Gy in 19 fractions did not meet non-inferiority criteria (HR 1.20,90% CI 0.99-1.46) and should not be used 3
• Alternative validated regimens include doses delivering 240-340 cGy per fraction 1, 2

Conventional Fractionation (When Moderate Hypofractionation Unavailable)

• Minimum 74 Gy for definitive treatment, with dose escalation to 78-80+ Gy improving biochemical control and delaying salvage hormonal therapy 1, 4

Salvage Radiotherapy Post-Prostatectomy

• Minimum 66 Gy to the prostatic fossa is recommended, with higher doses (>66.6 Gy) showing improved biochemical control in multivariate analysis (HR 0.60 for low-dose vs high-dose) 1

Mandatory Technical Requirements

Image-guided radiation therapy (IGRT) and intensity-modulated radiation therapy (IMRT) or more advanced techniques are absolutely required for safe delivery of any hypofractionated regimen. 1, 2, 4

Image Guidance

• Daily prostate localization must be performed using CT, ultrasound, implanted fiducials, electromagnetic targeting/tracking, or endorectal balloon 2, 4
• IGRT is particularly critical when doses ≥78 Gy are used to improve oncologic cure rates and reduce side effects 4

Treatment Planning

• Non-modulated 3-dimensional conformal techniques must be avoided due to increased toxicity risk 1, 2
• At least 2 dose-volume constraint points for rectum and bladder must be used (one at high-dose end, one in mid-dose range) 2
• Deviating from published reference study constraints is strongly discouraged due to risk of increased acute and late toxicity 2

Toxicity Profile

The 5-year cumulative incidence of RTOG Grade 2 or worse toxicity with moderate hypofractionation (60 Gy/20 fractions) versus conventional fractionation (74 Gy/37 fractions) shows no significant differences: 3

• Bowel toxicity: 11.9% vs 13.7%
• Bladder toxicity: 11.7% vs 9.1%
• No treatment-related deaths were reported in major trials 3

Critical Pitfalls to Avoid

• Never use single-fraction HDR monotherapy, as the Phase II trial demonstrated significantly worse outcomes (5-year biochemical disease-free survival 73.5%) and higher Grade 3 genitourinary toxicity compared to 2-fraction approaches (95% biochemical disease-free survival) 1
• Never omit ADT for high-risk disease, as the combination of EBRT plus 24-36 months ADT has Grade A evidence demonstrating improved overall survival, while radiation alone does not 4, 1
• Never use inadequate image guidance or non-IMRT techniques, as these significantly increase toxicity risk 1, 2
• Never exceed validated dose constraints from reference studies, as this increases acute and late toxicity 2
• Never treat high-risk patients with ultrahypofractionation outside clinical trials due to insufficient evidence 1, 2