Long term genitourinary toxicity following curative intent intensity-modulated radiotherapy for prostate cancer: a systematic review and meta-analysis

Abstract

Background: Recent studies have shown that radiation-induced pelvic toxicity often requires urological consultation. However, the 10-year incidence of genitourinary toxicity following intensity-modulated radiotherapy (IMRT) amongst patients with localised prostate cancer remains unclear. Hence, we conducted a systematic review and meta-analysis to determine the incidence of late genitourinary toxicity relying on Radiation Therapy Oncology Group (RTOG) and Common Terminology Criteria for Adverse Events (CTCAE) grade as well as the incidence of specific genitourinary toxicity. Secondary objectives involved quantifing the number of studies reporting 120-month follow-up endpoints, time to event analysis, predictive factors or economic evaluation.

Methods: Articles published from January 2008 to December 2021 describing prospective studies were systematically searched in MEDLINE, EMBASE and Cochrane (PROSPERO protocol CRD42019133320). Quality assessment was performed by use of the Cochrane Risk of Bias 2 Tool for RCTs and the Newcastle Ottowa Scale for non-RCTs. Meta-analysis was performed on the 60-month incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity, haematuria, urinary retention and urinary incontinence.

Results: We screened 4721 studies and six studies met our inclusion criteria. All included studies involved normofractionation, three included a hypofractionation comparator arm and none involved nodal irradiation. The pooled 60-month cumulative incidence of RTOG and CTCAE Grade ≥2 genitourinary toxicity were 17% (95% CI: 5-20%, n = 678) and 33% (95% CI: 27-38%, n = 153), respectively. The pooled 60-month cumulative incidence of Haematuria was 5% (95% CI: -4-14%, n = 48), Urinary incontinence 12% (95% CI: 6-18%, n = 194), Urinary retention 24% (95% CI: 9-40%, n = 10). One study reported time to event analyses, one reported predictive factors, no studies reported economic analysis or 120-month toxicity. There was considerable heterogeneity amongst the studies.

Conclusion: There are few high-quality studies reporting 60-month toxicity rates after IMRT. Conservative estimates of 60-month toxicity rates are high and there is need for longer follow-up and consistent toxicity reporting standards.

Fig. 1

Flow diagram of evidence acquisition in a systematic review of late genitourinary toxicity in prostate cancer patients treated with IMRT.

Fig. 2

Forrest plots of studies included in the meta-analysis demonstrating the 60-month incidence of RTOG and CTCAE ≥ 2 toxicity, haematuria, urinary incontinence and retention.

Fig. 3

Forrest plots of studies included in the meta-analysis comparing the 60-month incidence of RTOG amongst patients treated with hypofractionation and normofractionation intensity-modulated radiotherapy.

Fig. 4

Weighted summary bar plot and traffic light plot for included RCTs and non-RCT based on the Cochrane Risk of Bias 2 Tool and Newcastle Ottowa Score, respectively.

Fig. 5

Funnel plots of heterogeneity for studies included for meta-analysis of late RTOG and CTCAE genitourinary toxicity rates.