Patients with prostate cancer who are undergoing treatment may develop urethral complications over time regardless of treatment modality, according to a study.
“Combined modalities pose a heightened risk of developing urethral complications, while observation and radical prostatectomy have the lowest risk, with complications from surgery appearing earlier and stabilizing over time,” the researchers said.
A total of 47,387 men (median age 66 years) diagnosed with prostate cancer from 2002 to 2021 in the Alberta Cancer Registry were assessed for complications using the Discharge Abstract Database and the National Ambulatory Care Reporting System. Urethral complications referred to the development of stenosis, fistula, or a urethral procedure >30 days after treatment.
The research team allocated participants into the following treatment groups: radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT), cryotherapy (Cryo), RP plus EBRT, EBRT plus BT, Cryo plus EBRT, or medical treatment/observation (MT/O). They also compared urethral complications between groups using Cox regression.
A total of 3,140 patients developed urethral complications over a median follow-up of 79 months. Age (p<0.001), stage (p=0.001), and treatment modality (p<0.001) independently predicted such complications on multivariable Cox regression. Most treatment modalities also correlated with the development of complications when compared with MT/O. [J Urol 2026;216:654-662]
At 15 years, the highest incidence of urethral complications was observed for combined modalities. Specifically, EBRT plus Cryo (42 percent) showed the highest risk, followed by EBRT plus BT (26 percent), and RP plus EBRT (22 percent). The lowest risk was observed for MT/O (8 percent) and RP (9 percent).
Complications after RP plateaued at 10 years, but other modalities continued to amass complications in the long term.
“Urethral complications should be discussed explicitly during shared decision-making and incorporated into survivorship planning,” the researchers said.
Stage and age
Apart from treatment modality, patient age at the time of diagnosis and tumour stage also correlated independently with the development of urethral complications.
Compared with stage I, all the other stages displayed at least a 25-percent increased risk of developing complications. This association could have been partially driven by the need for more aggressive treatment (ie, broader radiation templates, BT boosts, wider surgical margins, etc) in more locally advanced or aggressive tumours, especially in patients undergoing combined treatment.
Furthermore, a study by Elliott and colleagues reported age and obesity to be predictive of urethral strictures after prostate cancer treatment. [J Urol 2007;178:529-534]
“For radiated patients, this would support the contentious belief that age is associated with increased radiosensitivity,” the researchers said. [BMC Geriatr 2018;18:105; Clin Interv Aging 2023;18:689-711]
“Our study suggests that age may play a role contributing to an increased risk of urethral complications independent of treatment modality and may warrant inclusion into pretreatment counselling,” they added.
Limitations
The current study was limited by the use of administrative data, which cannot establish a causal relationship between treatment and each urethral event, distinguish adjuvant from salvage therapy, or measure the full burden of repeat procedures, according to the researchers.
Additionally, estimates could have been influenced by care received elsewhere and differences in treatment era, selection, and follow-up, while Kaplan-Meier methods could have overestimated the absolute risk with competing mortality.