A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

Ahmed, Awad A.; Egleston, Brian L.; Alçântara, P.; Li, Linna; Pollack, Alan; Horwitz, Eric M.; Buyyounouski, Mark K.

doi:10.1016/j.ijrobp.2013.03.020

Cited by 25 publications

(22 citation statements)

References 20 publications

(22 reference statements)

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“…These results suggest that the dose to the entire bladder is a surrogate for the importance of the dose to the bladder wall. From a pathophysiological point of view, it seems evident that dose hotspots to the bladder wall are more indicative of side effects [ 22 – 23 ]. Anticoagulants use was significantly related to hematuria in the univariable analysis, which is in accordance with a study by Palorini [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients

et al. 2018

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Background and purposeIncontinence, hematuria, voiding frequency and pain during voiding are possible side effects of radiotherapy among patients treated for prostate cancer. The objective of this study was to develop multivariable NTCP models for these side effects.Material and methodsThis prospective cohort study was composed of 243 patients with localized or locally advanced prostate cancer (stage T1-3). Genito-urinary (GU) toxicity was assessed using a standardized follow-up program. The GU toxicity endpoints were scored using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) scoring system. The full bladder and different anatomical subregions within the bladder were delineated. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyze dose volume effects on the four individual endpoints.ResultsIn the univariable analysis, urinary incontinence was significantly associated with dose distributions in the trigone (V55-V75, mean). Hematuria was significantly associated with the bladder wall dose (V40-V75, mean), bladder dose (V70-V75), cardiovascular disease and anticoagulants use. Pain during urinating was associated with the dose to the trigone (V50-V75, mean) and with trans transurethral resection of the prostate (TURP). In the final multivariable model urinary incontinence was associated with the mean dose of the trigone. Hematuria was associated with bladder wall dose (V75) and cardiovascular disease, while pain during urinating was associated with trigone dose (V75) and TURP. No significant associations were found for increase in voiding frequency.ConclusionsRadiation-induced urinary side effects are associated with dose distributions to different organs as risk. Given the dose effect relationships found, decreasing the dose to the trigone and bladder wall may reduce the incidence of incontinence, pain during voiding and hematuria, respectively.

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Section: Discussionmentioning

confidence: 99%

Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients

et al. 2018

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“…Ahmed et al. reported that age >68 years was associated with late grade 2 GU toxicity and advocated risk‐adapted dose constraints based on patient age .…”

Section: Discussionmentioning

confidence: 99%

Long‐term outcomes in patients treated with proton therapy for localized prostate cancer

et al. 2017

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The aim of this retrospective study was to report long‐term clinical outcomes in patients treated with proton therapy (PT) for localized prostate cancer. Between 2001 and 2014, 1375 consecutive patients were treated with PT. Patients were classified into prognostic risk groups based on the National Comprehensive Cancer Network criteria. Freedom from biochemical relapse (FFBR), cancer‐specific survival (CSS) and incidence of late gastrointestinal (GI)/genitourinary (GU) toxicities were calculated. Multivariate analysis was performed to identify clinical prognostic factors for FFBR and late toxicities. The median follow‐up period was 70 months (range, 4–145 months). In total, 99% of patients received 74 Gy (relative biologic effectiveness [RBE]); 56% of patients received neoadjuvant androgen deprivation therapy. For the low‐, intermediate‐, high‐, and very high‐risk groups, 5‐year FFBR was 99% (95% confidence intervals [CI], 96–100%), 91% (95% CI, 88–93%), 86% (95% CI, 82–89%), and 66% (95% CI, 53–76%), respectively, and 5‐year CSS was 100% (95% CI, 100–100%), 100% (95% CI, 100–100%) , 99% (95% CI, 97–100%), and 95% (95% CI, 94–98%), respectively. Patient age, T classification, Gleason score, prostate‐specific antigen, and percentage of positive cores were significant prognostic factors for FFBR. Grade 2 or higher GI and GU toxicities were 3.9% and 2.0%. Patient age was a prognostic factor for both late GI and GU toxicities. This study represents the largest cohort of patients treated with PT for localized prostate cancer, with the longest follow‐up to date. Our results demonstrate that the biochemical control of PT is favorable particularly for high‐ and very high‐risk patients with lower late genitourinary toxicity and indicates the necessity of considering patient age in the treatment protocols.

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“…After external beam radiation therapy, incidence of late GU toxicity (≥grade 2) ranges from 10 to 30% ( 3 – 5 ). Previous studies have recognized older age ( 6 ), higher radiation dose ( 5 ), and prior transurethral resection of the prostate (TURP) ( 7 ) as risk factors for late GU toxicity following external beam radiotherapy. GU toxicities are rarely an isolated finding, occurring more commonly as a complex of lower urinary tract symptoms (LUTS) ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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A Novel Method for Predicting Late Genitourinary Toxicity After Prostate Radiation Therapy and the Need for Age-Based Risk-Adapted Dose Constraints

Cited by 25 publications

References 20 publications

Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients

Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients

Long‐term outcomes in patients treated with proton therapy for localized prostate cancer

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

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