Long-Term Risk of Hip Complications After Radiation Therapy for Prostate Cancer: A Dose-Response Study

Abstract

Purpose: The aim of the present study was to analyze the long-term incidence of hip complications after external beam radiation therapy compared with age-matched controls from the general population. We also investigated whether there were any dose-response associations.

Methods and materials: A total of 349 patients with prostate cancer treated to curative dose with external beam radiation therapy between 1997 and 2002 were included in the study. Physical and fractionation-corrected dose-volume descriptors were derived for the femoral heads, pubic bone, and sacrum. Information on skeletal events was collected for the patients and 1661 matched controls through the Prostate Cancer database Sweden. Uni- and multivariable Cox proportional hazard regressions were used to analyze the time to event.

Results: Data from 346 patients were available for analysis. The median mean physical dose and corresponding equivalent 2-Gy/fraction dose (EQD2) to the femoral heads were 35.5 Gy and 28.7 Gy, respectively. The median follow-up time was 16.0 years. During the follow up, 12 hip fractures occurred. Hip osteoarthritis was diagnosed in 36 cases, with 29 cases leading to replacement surgery. No increased risk of hip fractures was found. Hip osteoarthritis was the only event for which a statistically significant difference was found between the irradiated cohort and the controls (cause-specific hazard ratio: 1.56; 95% confidence interval, 1.07-2.26; P = .02). The cumulative incidence of osteoarthritis at 10 years was 8.1% and 4.9% in the irradiated cohort and the controls, respectively. A significant relationship between osteoarthritis and the volume of the femoral head receiving ≥40 Gy (ie, EQD2) was found.

Conclusions: In this study of 346 patients treated with conventional radiation therapy, we found no increased risk of hip fracture but an increased risk of clinically relevant osteoarthritis at long-term follow up. Our results indicate a dose-response relationship between osteoarthritis and the volume of the femoral head receiving an EQD2 dose of ≥40 Gy.

Figure 1

Example of shrinking 4-field box treatment planning technique + 2 lateral beams for delivery of a total prescribed dose of 78 Gy to the prostate. Structures shown are CTV_prostate (dark blue), CTV_{seminal vesicles} (pink), PTV_{70 Gy} (green), PTV_{66 Gy} (red), PTV_{50 Gy} (light blue), rectum (green), femoral heads (black), pubic bone (black), and sacrum (black). Treatment plans (prescribed doses): Phase 1 (50 Gy; solid white field borders), phase 2 (16 Gy; dashed), phase 3 (4 Gy; dotted), and phase 4 (lateral beams only; 8 Gy; dashed-dotted). Field borders are drawn without divergence for clarity. Abbreviations: CTV = clinical target volume; PTV = planning target volume. (A color version of this figure is available at https://doi.org/10.1016/j.adro.2020.09.011.)

Figure 2

Cumulative incidence of osteoarthritis in the irradiated cohort versus the controls with bone metastases and death as competing events