Clinical Characteristics and Management of Late Urinary Symptom Flare Following Stereotactic Body Radiation Therapy for Prostate Cancer

Abstract

Purpose: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. While acute post-SBRT urinary symptoms are well recognized, the late genitourinary toxicity of SBRT has not been fully described. Here, we characterize the clinical features of late urinary symptom flare and recommend conservative symptom management approaches that may alleviate the associated bother.Methods: Between February 2008 and August 2011, 216 men with clinically localized prostate cancer were treated definitively with SBRT at Georgetown University Hospital. Treatment was delivered using the CyberKnife with doses of 35–36.25 Gy in five fractions. The prevalence of each of five Common Terminology Criteria for Adverse Events (CTCAE) graded urinary toxicities was assessed at each follow-up visit. Medication usage was documented at each visit. Patient-reported urinary symptoms were assessed using the American Urological Association (AUA) symptom score and the Expanded Prostate Cancer Index Composite (EPIC)-26 at 1, 3, 6, 9, 12, 18, and 24 months. Late urinary symptom flare was defined as an increase in the AUA symptom score of ≥5 points above baseline with a degree of severity in the moderate to severe range (AUA symptom score ≥15). The relationship between the occurrence of flare and pre-treatment characteristics were examined.Results: For all patients, the AUA symptom score spiked transiently at 1 month post-SBRT. Of the 216 patients, 29 (13.4%) experienced a second transient increase in the AUA symptom score that met the criteria for late urinary symptom flare. Among flare patients, the median age was 66 years compared to 70 for those without flare (p = 0.007). In patients who experienced flare, CTCAE urinary toxicities including dysuria, frequency/urgency, and retention peaked at 9–18 months, and alpha-antagonist utilization increased at 1 month post-treatment, rose sharply at 12 months post-treatment, and peaked at 18 months (85%) before decreasing at 24 months. The EPIC urinary summary score of flare patients declined transiently at 1 month and experienced a second, more protracted decline between 6 and 18 months before returning to near baseline at 2-year post-SBRT. Statistically and clinically significant increases in patient-reported frequency, weak stream, and dysuria were seen at 12 months post-SBRT. Among flare patients, 42.9% felt that urination was a moderate to big problem at 12 months following SBRT.Conclusion: In this study, we characterize late urinary symptom flare following SBRT. Late urinary symptom flare is a constellation of symptoms including urinary frequency/urgency, weak stream, and dysuria that transiently occurs 6–18 months post-SBRT. Provision of appropriate anticipatory counseling and the maintenance of prophylactic alpha-antagonists may limit the bother associated with this syndrome.

Late urinary toxicity modeling after stereotactic body radiotherapy (SBRT) in the definitive treatment of localized prostate cancer

“…Recently, Woo et al reported a transient late urinary flare in 13.4% of patients who received ultra-hypofractionated SBRT for localized prostate cancer [11]. This was clinically similar to that described in patients treated with low dose rate (LDR) interstitial brachytherapy [12–15] and consisted of an abrupt increase in urinary symptoms following a post treatment nadir, which subsequently returned to previous nadir with conservative management.…”

“…However, a recent Surveillance, Epidemiology, and End Results Program (SEER) based analysis has called into question the safety of these treatments in terms of long term urinary toxicity as compared to conventionally fractionated IMRT [22]. Recently, we reported QOL outcomes for patients treated according to our institutional protocol and noted a small subset of patients who developed a late increase in urinary symptoms following a post treatment nadir that subsequently returned to previous nadir, termed late urinary flare [11]. These patients experienced higher rates of CTCAE-graded dysuria, urinary frequency, urgency, and retention in the first 2 years of follow up after prostate SBRT, and demonstrated significant declines in QOL in the EPIC urinary domain.…”

Comparison of Late Urinary Symptoms Following SBRT and SBRT with IMRT Supplementation for Prostate Cancer

“…Previous work demonstrated an association of delayed radiation-induced cystourethritis and the development of urinary symptoms 1 year after hypofractionated radiotherapy [30], which is consistent with our current finding that hypofractionated radiotherapy results in more severe urinary toxicity compared to conventionally fractionated radiotherapy. The role of inflammation in the pathogenic process of late urinary toxicities is further supported by the observation that these symptoms respond well to oral corticosteroids (dexamethasone 4 mg/day for 1 week followed by 2 mg for 1 week) [16]. Future studies should explore the correlation between target volume dose distribution and late urinary symptoms [31].…”

“…This phenomenon is classically described as late urinary flare (LUF), which is defined as a moderate (Grade ≥ 2) late genitourinary toxicity [13,14]. While much of the literature discusses flares in relation to intensity-modulated radiation therapy (IMRT) and brachytherapy treatment modalities [15], LUF has been recently associated with stereotactic body radiation therapy (SBRT) treatment, which manifests as a symptom cluster of dysuria, urinary frequency, urinary urgency, and weak stream occurring anywhere from 6 to18 months after treatment completion [16]. …”

Stereotactic radiotherapy for prostate cancer: A review and future directions

“…The majority of studies evaluated here reported at least one instance of late grade 3 or higher urinary toxicity, often requiring instrumentation or transurethral resection of the prostate (TURP). This flare phenomenon has been found to peak between 12 and 18 mo post-treatment, though symptoms resolve by 24 mo in a majority of cases[31]. However, this trend remains a concern and should be further elucidated prior to large-scale adoption of SBRT for low- and intermediate-risk prostate cancer.…”