No Apparent Increased Risk of Myelodysplastic Syndrome With Definitive Radiotherapy in Prostate Cancer


Key Points

  • Patients receiving radiation therapy did not appear to be at greater risk of myelodysplastic syndrome compared with surgery patients, although a borderline increased risk was observed among brachytherapy patients.
  • Age was an independent predictor of myelodysplastic syndrome risk.

Exposure to ionizing radiation has been associated with increased risk of myelodysplastic syndrome, and it remains unclear whether radiation doses used in prostate cancer treatment result in increased risk. In a retrospective cohort study reported in the Journal of the National Cancer Institute, Mukherjee et al found no significantly increased risk of myelodysplastic syndrome over relatively short-term follow-up.

Study Details

The study involved analysis of prostate cancer patients diagnosed between 1986 and 2011 at Cleveland Clinic. Myelodysplastic syndrome frequency was compared among patients undergoing radical prostatectomy, those receiving radiotherapy with either external-beam radiotherapy or prostate interstitial brachytherapy, and in the general population using national and state population-based registries. Competing risk regression analyses were used to determine the cumulative risk of developing myelodysplastic syndrome.

Of 10,924 patients included in the analysis, 5,119 (47%) received radiation, including 2,183 (43%) in the external-beam radiotherapy group and 2,936 (57%) in the interstitial brachytherapy group, and 5,805 (53%) were treated with radical prostatectomy. Patients receiving radiation were older (median age, 69 years for those receiving external-beam radiotherapy and 67 years for those receiving brachytherapy vs 60 years in those receiving prostatectomy; P < .001 for trend), and the external-beam radiotherapy group had the greatest proportions of patients with clinical stage T2b/2c or T3 disease, Gleason score > 8, and receiving androgen-deprivation therapy, and had the highest median prostate-specific antigen levels at baseline.

Risk for Radiation vs Surgery

Median follow-up for all patients was 3.0 years, including 6.8 years in the external-beam radiotherapy group, 2.5 years in the brachytherapy group, and 1.9 years in the surgery group (P < .001 for trend). Overall, 31 cases of myelodysplastic syndrome were observed. Cumulative risk for developing myelodysplastic syndrome increased with duration of follow-up. Median time to development of myelodysplastic syndrome was 8.9 years in the external-beam radiotherapy group, 8.2 years in the brachytherapy group, and 13.0 years in the surgery group (P = .05 for trend).

On univariate analysis, greater age (hazard ratio [HR] = 1.14, P < .001) and radiotherapy exposure (HR = 3.44, P = .007) were significantly associated with development of myelodysplastic syndrome. In the multivariate risk regression model, whereas greater age (HR = 1.13, P < .001) remained an independent factor associated with myelodysplastic syndrome, radiation therapy overall did not (HR = 1.63, P = .35). The hazard ratio for external-beam radiotherapy vs surgery was not significant (1.34, P = .59), whereas that for brachytherapy vs surgery was of borderline significance (HR = 2.76, P = .08).

Risk vs General Population

The age-adjusted incidence rate for myelodysplastic syndrome was lower in the Cleveland Clinic patients than in the general population in the Surveillance, Epidemiology, and End Results (SEER) 17 program for all patients combined and according to external-beam radiotherapy, brachytherapy, or surgery treatment except for external-beam radiotherapy patients in the 70- to 79-year-old age group (57 vs 30/100,000 population).

Compared with the Ohio Cancer Incidence Surveillance System registry, age-adjusted incidence rates in the prostate cancer cohort were higher among brachytherapy patients in the 60- to 69-year-old group (6.5 vs 3.2/100,000), for all patients and all radiation patients (26 and 34 vs 10.3/100,000), as well as for all individual treatment groups, in the 70- to 79-year-old group, and for all patients and all radiation patients (38 and 39 vs 10.2/100,000), as well as for all individual treatment groups, in the ≥ 80-year-old group.

The investigators concluded, “With relatively short follow-up, prostate cancer patients definitively treated with radiation did not appear to have a statistically increased risk of subsequent [myelodysplastic syndrome].”

Mikkael A. Sekeres, MD, MS, of the Cleveland Clinic Taussig Cancer Institute, is the corresponding author for the Journal of the National Cancer Institute article.

Ohio cancer incidence data used in these analyses were obtained from the Ohio Cancer Incidence Surveillance System, a cancer registry partially supported by the National Program of Cancer Registries at the Centers for Disease Control and Prevention.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.