Our study cohort consists of 86,038 patients, 60,134 who were radiated and 25,904 who underwent observation. The median follow up time was 94 months. The characteristics of the cohort are described in Table 2 (web only). The observation (compared to radiated) patients were older, more likely to reside in a low income area, and had more well differentiated cancers with lower T stage. Of the patients who were radiated, 9% had a prior procedure for obstruction/stricture; of the observation patients, 28% had a similar procedure. Of the 60,134 radiated patients, 39,690 patients were treated with EBRT, 12,738 with brachytherapy, and 7,706 with EBRT + brachytherapy.
Of the various grade 2–4 GU toxicities among all patients, the most common events were obstruction/stricture (36/1000 person-years) and cystitis (1.6/1000 person-years). The rates of GU fistula (0.1/1000 person-years) and incontinence (0.7/1000 person-years) were very low.
Regarding the time course of GU toxicities, the elevated risk persisted beyond 10 years (). shows that the adjusted elevated risk of GU toxicity for radiation versus observation increases with time. The adjusted risk ratio is 2.49 (95% CI 2.00–3.11) for 10 years and beyond, indicating that GU toxicity after radiation is a long- term problem.
Figure 1A: Event Rate of Genitourinary Toxicity After Radiation by Treatment Group for all Patients
Adjusted Risk Ratio for GU Toxicity, Radiation versus Surveillance by Time Interval
demonstrates that having had procedures for obstruction/stricture prior to radiation increases the risk of GU toxicity afterwards. 10 years after radiation, the cumulative 10-year risk of GU toxicity for patients who had procedures for obstruction/stricture prior to radiation was 38.7%, and for those with no such history, 20.1%.
Effect of Procedures for Obstruction/Stricture Prior to Radiation on Incidence of GU Toxicity Following Radiation
The brachytherapy modalities are associated with a higher risk of GU toxicity, as summarized in . Brachytherapy + EBRT (60 events/1000 person-years) had a higher rate of GU toxicity than brachytherapy (43/1000 person-years) or EBRT (35/1000 person-years). Among the external beam modalities, the rates of GU toxicity were relatively similar: 3DCRT (37/1000 person-years), IMRT (32/1000 person-years), protons (34/1000 person-years). For observation, the rate was 32/1000 person-years. The 5- and 10- year cumulative incidences for any first GU toxicity were: for all radiated patients (14.4% and 21.7%), brachytherapy + EBRT (19.4% and 27.8%), brachytherapy (17.6% and 23.5%), 3DCRT (12.7% and 20.1%), IMRT (12.8% and no 10- year data), protons (12.6% and no 10- year data), and observation (14.3% and 19.9%).
Event Rate of Genitourinary Toxicity by Radiation Therapy Modalities and Prior GU Procedures
Variables associated with worse GU toxicity were: radiation (at all year intervals after radiation), earlier year of cancer diagnosis, worse comorbidity score, older age, state buy- in (a measure of poverty), poor tumor differentiation, prior procedure for obstruction/stricture (the single strongest predisposing factor). Southern region was associated with less GU toxicity. Higher T stage and marital status were not significant factors (Table 3).
In pairwise comparisons, all the radiation modalities resulted in more toxicity than observation. Brachytherapy + EBRT had more toxicity than brachytherapy (risk ratio: 1.23; 95% CI, 1.11–1.37). Brachytherapy, whether alone or combined with EBRT, had significantly more GU toxicity than the EBRT modalities. Among the EBRT modalities, 3DCRT had more toxicity than IMRT (risk ratio:1.25; 95% CI,1.08–1.44). Protons were not significantly different from either IMRT or 3DCRT. These relationships are illustrated graphically in .