Impact of image-guided radiation therapy with intraprostatic seeds on long-term toxicity in prostate cancer patients undergoing risk-adapted intensification therapy.

OBJECTIVES

To evaluate how the implementation of intensity-modulated/image-guided RT (IMRT/IGRT) with intraprostatic seeds can impact the risk of late gastrointestinal (LGI) and genitourinary (LGU) toxicity in prostate cancer (PCa) patients treated with dose-escalation RT.

MATERIALS /

METHODS

Retrospective analysis of a prospective cohort of 1,010 men treated within a risk-adapted, intensification program with a minimum follow-up (FU) of 5 years. The median radiation dose to prostate was 79.5 Gy (IQR: 75.0, 80.3). Short-term ADT (STADT, n = 165) and long-term ADT (LTADT, n = 385) were administered to intermediate- and high-risk patients, respectively. Late toxicities were assessed using the EORTC/RTOG criteria. Kaplan-Meier analysis: to calculate the cumulative incidence of late toxicities; Cox proportional regression model: to estimate hazard ratios (HRs).

RESULTS

Median FU was 116 months (IQR: 88-133). The median RT dose for IMRT/IGRT was 80.0 Gy (IQR 79.1, 81.2) and 78.0 Gy (IQR 73.1, 79.6), (p = 0.001) for those treated with 3DCRT. The 10-year Kaplan-Meier grade ≥ 2 LGI and LGU toxicities were 10% (95% confidence interval [CI] 8-12) and 16% (95% CI 14-18), respectively. The multivariate analysis (MVA) showed that the use of IMRT/IGRT with intraprostatic seeds was a significant protective factor for grade ≥ 2 LGI toxicity (HR: 0.66, 95%CI: 0.46-0.95, p = 0.021), despite the higher radiation dose in the IMRT/IGRT group. However, its impact on decreasing grade ≥ 2 LGU toxicity did not achieve statistically significance (13% vs 18%; p = 0.053, HR 0.88). A prior transurethral resection of the prostate (TURP) (HR 1.98, 95% CI: 1.30-2.59, p = 0.002) and the presence of acute grade ≥ 2 GU complications (HR:1.76, 95% CI: 1.20-2.9, p = 0.003) were associated with a higher incidence of grade ≥ 2 LGU toxicity, while LTADT was significantly associated with a lower risk of GU complications (HR:0.66, 95% CI: 0.46-0.95, p = 0.021).

CONCLUSION

The study confirms that IMRT/IGRT with intraprostatic fiducial markers significantly reduces grade ≥ 2 late GI toxicity, and appears to prevent an increase in GU toxicity rates despite dose escalation.