Patient-reported Urinary Symptoms Research Articles

Long-Term Urinary Toxicity Follow-Up of Combined External Beam Radiation and Cs-131 LDR Brachytherapy Boost for Prostate Cancer

To evaluate and update our institutional data on chronic patient-reported urinary symptoms in patients with prostate cancer treated with combined external beam radiation therapy (EBRT) and Cesium-131 (Cs-131) LDR brachytherapy boost. Patients treated from September 2006-July 2022 and with at least 6 months of follow-up were analyzed. Patients filled out the Expanded Prostate Cancer Index Composite (EPIC) questionnaire pre-treatment and at each scheduled follow-up. Mean EPIC urinary scores were calculated for urinary summary, urinary function, urinary bother, urinary incontinence, and urinary irritative/obstructive domains. Changes of 7-points or more in mean domain scores were deemed clinically significant. The prevalence of urinary bleeding was calculated and bleeding occurring more than "about once a week" ("more than once a week", "about once a day", and "more than once a day") was deemed clinically significant. Outcomes were analyzed at each follow-up timepoint using paired t-test. A total of 341 patients with prostate cancer were included in the analysis of which 183 were intermediate-risk and 158 high-risk. 174 patients were treated with tri-modality therapy, and SpaceOAR was used in 108 patients. Long-term statistically significant decreases in mean EPIC QOL scores were seen in urinary summary, urinary function, urinary bother, urinary incontinence, and urinary irritative/obstructive domains at 6 months, with clinically and statistically significant decreases in urinary function and urinary incontinence at 6 months (86±17.4, 83.4±22.2 respectively) and up to 18 months post-treatment (84.8±17.4, 83.6±20.7 respectively) compared with pre-treatment scores (93.1±10.7, 90.8±14.8 respectively), with both domains returning to clinical baseline at 24 months. Urinary irritative/obstructive mean scores clinically and significantly decreased at 9 months (77±17.4) compared to pre-treatment (84.7±13.5), returning to clinical baseline at 12 months. The prevalence of clinically significant urinary bleeding at 6, 12, 24, 36, 48, and 60 months was 1.3%, 2.6%, 3.7%, 0.7%, 0.9%, and 2.3% respectively. At the median follow-up of 42 months (IQR 54, 18-72), mean EPIC scores were clinically improved (≥7-point increase) from pre-treatment baseline in 15-30% of patients across the analyzed urinary domains. Long-term patient-reported clinically significant decreases in urinary function and urinary incontinence mean EPIC scores occurred up to 18 months following combined external beam radiation and Cs-131 prostate brachytherapy and returned to baseline at 24 months, while clinically significant decrease in urinary irritability/obstructive mean scores occurred at 9 months and returned to baseline at 12 months. At 42 months follow-up, mean urinary domain scores improved from pre-treatment baseline in 15-30% of patients.

Comparing Patient-Reported Urinary Symptoms after Prostate Radiation Therapy across Different Radiation Modalities

<h3>Purpose/Objective(s)</h3> Comparative quality of life outcomes of different types of radiation therapy for prostate cancer have not been well studied. Herein we provide results comparing patient-reported urinary symptoms across four commonly used modalities: external beam radiotherapy (EBRT) using a moderately or conventionally fractionated course, brachytherapy, EBRT with a brachytherapy boost, and stereotactic body radiotherapy (SBRT). <h3>Materials/Methods</h3> As part of routine care at our institution, urinary and gastrointestinal symptoms are prospectively collected from patients receiving radiotherapy for prostate cancer using the validated Prostate Cancer Symptom Indices at each visit starting at consultation and continuing into follow-up. Patient-reported urinary symptoms including frequency, incontinence, dysuria, urgency, and nocturia were collected between 2006-2019. This included data from initial consult (baseline) and multiple follow-up time points. Data collected between 2-3 months after finishing radiotherapy was used for the 3-month time point. Similarly, data collected between 4-6, 10-12, and 19-24 months were used for the 6 month, 1 year, and 2 year time points. As validated in prior studies, a score of 3 or higher indicated clinically meaningful symptoms. <h3>Results</h3> 1059 patients reported urinary symptoms and were used for this analysis. 587 (55%) received EBRT alone, 144 (14%) received brachytherapy alone, 151 (14%) received EBRT with brachytherapy boost, and 177 (17%) were treated with SBRT. The percentage of patients reporting clinically meaningful symptoms was highest at baseline (59-89%) and lowest at 2 years (13-38%). For patients receiving EBRT alone and brachytherapy alone, most symptoms were found to peak 3-6 months after radiotherapy, with a slow decline thereafter. At two years for these modalities, symptoms were near or below baseline. These rates were generally higher for brachytherapy across all types of urinary symptoms. For patients treated with EBRT plus brachytherapy boost incontinence remained at or near baseline, frequency peaked at 3 months, and nocturia, urgency, and dysuria peaked at 1 year. For patients treated with SBRT all urinary symptoms saw a gradual increase from baseline after radiotherapy throughout the entire two-year study period. <h3>Conclusion</h3> From these data, we see that urinary symptom trajectory is distinct among radiation therapy modalities. These results support careful consideration of baseline urinary symptoms when discussing treatment recommendations.

Minimal Patient-Reported Side Effects for a Chemoablative Gel (UGN-102) Used as Frontline Treatment in Adults with Nonmuscle-Invasive Bladder Cancer

Optima II ("OPTimized Instillation of Mitomycin for Bladder Cancer Treatment," clinicaltrials.gov: NCT03558503) was a phase 2b trial evaluating a nonsurgical alternative as a primary treatment for nonmuscle-invasive bladder cancer (NMIBC). Patients received 6 weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. This is the first study to report on patient-reported side effects of UGN-102. Sixty-three patients enrolled in Optima II from 20 sites. Of these 63 patients, 44 were in the cohort completing a quarterly patient-reported outcome measure assessing side effects. Changes in side effects were evaluated using the Wilcoxon signed-rank test. Associations of 3-month outcomes with demographic and clinical characteristics were examined with regression, controlling for baseline values. Ten of 44 patients (23%) were interviewed after the trial to understand tolerability for future patients making treatment decisions. Transcripts were double-coded using standard methods. In the patient-reported outcome measure cohort (44), 61% were men, 57% aged 65+ years and 89% were non-Hispanic White. UGN-102 did not cause decrements in patient-reported urinary symptoms, bloating/flatulence or malaise at the primary endpoint of 3 months. Sexual function mildly worsened. Future health worries improved. Demographics were not correlated with changes. Clinically, sexual function was correlated with new NMIBC and bloating/flatulence was associated with transurethral resection of bladder tumor within 12 months. In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients and would choose the gel over surgery. A nonsurgical, chemoablative gel (UGN-102) used as a primary treatment for NMIBC offers a more patient-centered therapeutic approach than standard treatments.

MP54-06 LONGITUDINAL HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN ADULTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER RECEIVING A CHEMOABLATIVE GEL AS A PRIMARY TREATMENT (OPTIMA II: PHASE 2B, SINGLE ARM, OPEN-LABEL TRIAL)

You have accessJournal of UrologyCME1 May 2022MP54-06 LONGITUDINAL HEALTH-RELATED QUALITY OF LIFE OUTCOMES IN ADULTS WITH NON-MUSCLE-INVASIVE BLADDER CANCER RECEIVING A CHEMOABLATIVE GEL AS A PRIMARY TREATMENT (OPTIMA II: PHASE 2B, SINGLE ARM, OPEN-LABEL TRIAL) Angela Smith, Ramsankar Basak, Dana Mueller, Robert Lipman, Randall Teal, Alison Hilton, Kara Giannone, Myra Waheed, and Angela Stover Angela SmithAngela Smith More articles by this author , Ramsankar BasakRamsankar Basak More articles by this author , Dana MuellerDana Mueller More articles by this author , Robert LipmanRobert Lipman More articles by this author , Randall TealRandall Teal More articles by this author , Alison HiltonAlison Hilton More articles by this author , Kara GiannoneKara Giannone More articles by this author , Myra WaheedMyra Waheed More articles by this author , and Angela StoverAngela Stover More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002633.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Low-grade non-muscle-invasive bladder cancer (LG NMIBC) is treated with transurethral resection of the bladder tumor (TURBT), which can worsen health-related quality of life (HRQOL). The trial “OPTimized Instillation of Mitomycin for Bladder Cancer Treatment” (Optima II, clinicaltrials.gov: NCT03558503) is a Phase 2b, open label, multicenter trial evaluating a nonsurgical alternative as a primary treatment. Patients receive six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel. We report on HRQOL changes at the primary endpoint of 3 months. METHODS: Of 63 patients enrolled in the Optima II trial, 44 were in the HRQOL cohort and completed quarterly questionnaires (61% men, 57% age 65+, and 89% non-Hispanic White). Longitudinal changes were evaluated using the Sign test and correlations with demographic and clinical characteristics with regression. Ten patients (23%) were interviewed and transcripts were double-coded using standard methods. RESULTS: The chemoablative reverse thermal gel did not cause decrements in patient-reported urinary symptoms, bloating/flatulence, or malaise (Figure). Sexual function mildly worsened. Demographic and clinical characteristics were not correlated with HRQOL changes. By 3 months, 31/44 (70%) LG NMIBC patients achieved a complete response (negative endoscopic examination, cytology, and for-cause biopsy). In interviews, patients appreciated a nonsurgical alternative, would recommend the gel to other patients, and would choose the gel over TURBT. CONCLUSIONS: Adults with LG NMIBC receiving a nonsurgical, chemoablative gel as a primary treatment maintained their HRQOL through 3 months, and interviewed patients would recommend the gel to other patients. A Phase 3 trial is warranted. Source of Funding: Bladder Cancer Advocacy Network Patient Survey Network Award, supported by Urogen Pharma © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e928 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Angela Smith More articles by this author Ramsankar Basak More articles by this author Dana Mueller More articles by this author Robert Lipman More articles by this author Randall Teal More articles by this author Alison Hilton More articles by this author Kara Giannone More articles by this author Myra Waheed More articles by this author Angela Stover More articles by this author Expand All Advertisement PDF DownloadLoading ...

Health-related quality of life outcomes in adults with nonmuscle-invasive bladder cancer receiving a mitomycin-containing reverse thermal gel as a primary treatment (Optima II: Phase 2b, single-arm, open-label trial).

270 Background: The standard of care for low-grade non‐muscle‐invasive bladder cancer (LG NMIBC) is transurethral resection of the bladder tumor, which can worsen health‐related quality of life (HRQOL). The “OPTimized Instillation of Mitomycin for Bladder Cancer Treatment” (Optima II, clinicaltrials.gov: NCT03558503) is a Phase 2b, open label, single arm, multicenter trial evaluating a nonsurgical alternative as a primary treatment. Patients receive six weekly instillations of UGN-102, a mitomycin-containing reverse thermal gel with a sustained release time of up to 8 hours. We report on HRQOL changes between baseline and the primary endpoint of 3 months. Methods: A total of 63 patients enrolled in the Optima II trial at 20 sites in the U.S. and 2 sites in Israel between October 2018 and October 2020. Of the 63 patients enrolled, 44 were in the HRQOL cohort and completed a quarterly questionnaire. The QLQ-NMIBC24 has six subscales (urinary symptoms, malaise, future health worries, bloating and flatulence, sexual functioning, and male sexual problems) and five single items (intravesical treatment issues, sexual intimacy, worry about contaminating partner, sexual enjoyment, and female sexual problems) assessed with 24 items. Items were rescaled to 0-100 and reverse-coded so that higher scores indicate worse symptom burden. Longitudinal score changes were evaluated using the Sign test. We examined demographic and clinical characteristics associated with HRQOL change scores with regression modeling. A p-value of ≤0.01 was used. Results: The HRQOL cohort was 61% men, 57% age 65+, and 89% non-Hispanic White. Clinically, most LG NMIBC patients had multiple tumors (88%) with prior NMIBC episodes (77%), and two or more prior transurethral resection of bladder procedures (TURBT) (85%). Approximately half (55%) had their most recent TURBT surgery within 12 months of trial enrollment. No patients had missing HRQOL data at baseline or the primary end point of 3 months. The chemoablative reverse thermal gel used as a primary treatment did not cause decrements in patient-reported urinary symptoms, bloating/ flatulence, malaise, fever, general health, or future health worries. Sexual function mildly worsened between baseline and 3 months, and abated by 6 months. Demographic and clinical characteristics were not correlated with HRQOL change scores. By 3 months, 31/44 (70%) LG NMIBC patients achieved a complete response (negative endoscopic examination, cytology, and for-cause biopsy) and 0 experienced a recurrence. By 12 months, 8/44 (18%) patients had a recurrence. Conclusions: Adults with LG NMIBC in a Phase 2b trial who received a mitomycin-containing reverse thermal gel with sustained release maintained their HRQOL through 3 months. A Phase 3 trial is warranted. Clinical trial information: NCT03558503.

Dosimetric correlations with urinary quality of life in patients receiving post-prostatectomy radiation therapy

Acute urinary toxicity is well-documented in individuals receiving post-prostatectomy radiation. However, dosimetric correlations between bladder dose and acute urinary symptoms in the post-prostatectomy setting have not been well-studied. We examined the relationship between bladder dosimetry and acute changes in individual urinary symptoms among men receiving post-prostatectomy radiation therapy. Patient-reported urinary symptoms were prospectively collected for 90 consecutive prostate cancer patients receiving post-prostatectomy radiation using the validated quality of life instrument Prostate Cancer Symptom Indices. Data were collected prior to treatment and weekly during treatment. Individual symptom scores were examined and a change in severity of an individual symptom (from baseline) of ≥ 2 points was considered clinically significant. DVHs were generated for all the patients. Receiver operating characteristic curves were generated to evaluate the ability of different dose-volume metrics to identify patients who developed individual urinary symptoms during radiation treatment from those who did not. Logistic regression was used to examine the relationship between dose-volume parameters and worsening of individual urinary symptoms. Worsening of individual urinary symptoms during radiation treatment was reported by 7% (urinary flow) to 29% (urgency) of patients. The relative bladder volume receiving moderate doses of radiation was associated with urgency (AUC 0.67 for V30 Gy). Dose-volume parameters were not significantly associated with flow, frequency, nocturia, or dysuria. There is an acute worsening of urinary symptoms among men receiving modern post-prostatectomy radiation. Worsening of urgency is associated with bladder dosimetry while flow, frequency, nocturia, and dysuria are not. This data can be used during treatment planning to reduce acute urinary toxicity during post-prostatectomy radiation.

Fitting NTCP models to bladder doses and acute urinary symptoms during post-prostatectomy radiotherapy

BackgroundTo estimate the radiobiological parameters of three popular normal tissue complication probability (NTCP) models, which describe the dose-response relations of bladder regarding different acute urinary symptoms during post-prostatectomy radiotherapy (RT). To evaluate the goodness-of-fit and the correlation of those models with those symptoms.MethodsNinety-three consecutive patients treated from 2010 to 2015 with post-prostatectomy image-guided intensity modulated radiotherapy (IMRT) were included in this study. Patient-reported urinary symptoms were collected pre-RT and weekly during treatment using the validated Prostate Cancer Symptom Indices (PCSI). The assessed symptoms were flow, dysuria, urgency, incontinence, frequency and nocturia using a Likert scale of 1 to 4 or 5. For this analysis, an increase by ≥2 levels in a symptom at any time during treatment compared to baseline was considered clinically significant. The dose volume histograms of the bladder were calculated. The Lyman-Kutcher-Burman (LKB), Relative Seriality (RS) and Logit NTCP models were used to fit the clinical data. The fitting of the different models was assessed through the area under the receiver operating characteristic curve (AUC), Akaike information criterion (AIC) and Odds Ratio methods.ResultsFor the symptoms of urinary urgency, leakage, frequency and nocturia, the derived LKB model parameters were: 1) D50 = 64.2Gy, m = 0.50, n = 1.0; 2) D50 = 95.0Gy, m = 0.45, n = 0.50; 3) D50 = 83.1Gy, m = 0.56, n = 1.00; and 4) D50 = 85.4Gy, m = 0.60, n = 1.00, respectively. The AUC values for those symptoms were 0.66, 0.58, 0.64 and 0.64, respectively. The differences in AIC between the different models were less than 2 and ranged within 0.1 and 1.3.ConclusionsDifferent dose metrics were correlated with the symptoms of urgency, incontinence, frequency and nocturia. The symptoms of urinary flow and dysuria were poorly associated with dose. The values of the parameters of three NTCP models were determined for bladder regarding four acute urinary symptoms. All the models could fit the clinical data equally well. The NTCP predictions of urgency showed the best correlation with the patient reported outcomes.

Correlation Between Bladder Dosimetry and Patient-Reported Acute Urinary Quality of Life During Modern Post-prostatectomy Image-Guided IMRT

Radical prostatectomy causes urinary symptoms including frequency and urgency, and post-prostatectomy (adjuvant or salvage) RT can further add to these symptoms during the RT treatment course. However, dosimetric correlations between bladder dose and acute urinary symptoms in the post-prostatectomy setting are understudied. The correlation between patient-reported urinary symptoms during RT and bladder dosimetry are the focus of this analysis. 90 consecutive patients treated from 2010-2015 with post-prostatectomy image-guided IMRT at a single institution were included. Patient-reported urinary symptoms using the validated Prostate Cancer Symptom Indices (PCSI) were collected pre-RT and weekly during treatment. PCSI assessed urinary frequency, urgency, flow, dysuria, incontinence, and nocturia graded on a Likert scale of 1 to 4 or 5. For this analysis, a ≥2 point increase in a symptom at any time during treatment compared to baseline was considered a clinically significant toxicity. Doses to the bladder and bladder wall were compared for patients who developed each urinary symptom vs those who did not. Receiver-operator curves were generated for each of those comparisons and the area under the curve (AUC) was used to assess the strength of the correlation. Patients were treated to a median dose of 66.6 Gy and 56% received concurrent ADT. Median time from surgery to RT was 1.6 years. Whole bladder doses (V10-V50) were correlated with worsening of urinary frequency, nocturia, incontinence, and urgency (Table) with AUC of 0.58-0.67. Higher bladder doses (≥V60) had a less strong association with AUC 0.55-0.67. There was no clear association between bladder dosimetry and urinary flow or dysuria. Results were similar with whole bladder and bladder wall dosimetry. In the setting of post-prostatectomy IMRT, low and medium doses to the bladder are correlated with acute worsening of urinary frequency, nocturia and urgency. These findings add to the understanding of bladder dose constraints and can help minimize acute urinary toxicity.Abstract 2619; TableWhole bladder dosimetry correlations with urinary symptomsSymptomVxAUCNo Toxicity (mean ± standard deviation)Toxicity (mean ± standard deviation)FrequencyV10 (cc)0.65106 ± 45144 ± 71V50 (cc)0.6266 ± 2677 ± 27NocturiaV10 (cc)0.64107 ± 50132 ± 56V50 (cc)0.6365 ± 2578 ± 32UrgencyV10 (%)0.6490 ± 1695 ± 13V50 (%)0.6556 ± 1968 ± 22IncontinenceV10 (%)0.5891 ± 1695 ± 9V50 (%)0.5959 ± 2165 ± 20 Open table in a new tab

Clinical and urodynamic assessment in patients with pelvic organ prolapse before and after laparoscopic sacrocolpopexy.

We hypothesized that patient-reported urinary symptoms and urodynamic evaluation improve after laparoscopic sacrocolpopexy (LSC) despite deeper vesicovaginal space dissection. This was a retrospective study of women with pelvic organ prolapse who underwent LSC from January 2013 to January 2016 in a tertiary center. Urinary function was clinically evaluated using the International Consultation on Incontinence Questionnaire - Short Form (ICIQ-SF), the Overactive Bladder Symptom Score (OABSS) and the Pelvic Floor Distress Inventory Questionnaire- - Short Form 20 (PFDI-20). Urodynamic assessment was performed before and 6months after surgery. The Wilcoxon signed-ranks test and the McNemar test were applied with p < 0.05 considered significant. A total of 155 patients were included in the study. Of these, 46 had urodynamic assessment before and after LSC. There were significant improvements after LSC in urodynamic storage phase parameters (higher volume at first desire, higher volume at strong desire, and larger bladder capacity) and voiding phase parameters (higher Q max, higher Q ave, lower P det Q max, increased voided volume and reduced postvoid residual urine volume). Clinically, there was a significant increase after LSC in stress urinary incontinence and a significant reduction in urgency urinary incontinence, overactive bladder and voiding dysfunction. Apart from increased stress urinary incontinence, there was an improvement in overall urinary function in terms of patient-reported symptoms and urodynamics, despite deep vesicovaginal space dissection. Hence, LSC is a viable surgical option for pelvic organ prolapse, restoring both level 1 and level 2 support without detrimental effects on urinary function.

OC-0535: How patient-reported urinary symptoms predict impairment of urinary QoL from RT for prostate cancer

OC-0535: How patient-reported urinary symptoms predict impairment of urinary QoL from RT for prostate cancer

Improved irritative voiding symptoms 3 years after stereotactic body radiation therapy for prostate cancer.

Background: Irritative voiding symptoms are common in elderly men and following prostate radiotherapy. There is limited clinical data on the impact of hypofractionated treatment on irritative voiding symptoms. This study sought to evaluate urgency, frequency, and nocturia following stereotactic body radiation therapy (SBRT) for prostate cancer.Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital were included in this study. Treatment was delivered using the CyberKnife® with doses of 35–36.25 Gy in five fractions. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at 1, 3, 6, 9, and 12 months post-treatment and every 6 months thereafter.Results: Two hundred four patients at a median age of 69 years received SBRT with a median follow-up of 4.8 years. Prior to treatment, 50.0% of patients reported moderate to severe lower urinary tract symptoms (LUTS) and 17.7% felt that urinary frequency was a moderate to big problem. The mean prostate volume was 39 cc and 8% had prior procedures for benign prostatic hyperplasia. A mean baseline IPSS-irritative (IPSS-I) score of 4.8 significantly increased to 6.5 at 1 month (p < 0.0001), however returned to baseline at 3 months (p = 0.73). The IPSS-I score returned to baseline in 91% of patients by 6 months and 96% of patients by 2 years. Transient increases in irritative voiding symptoms were common at 1 year. The mean baseline IPSS-I score decreased to 4.4 at 24 months (p = 0.03) and 3.7 at 36 months (p < 0.0001). In men with moderate to severe LUTS (IPSS ≥ 8) at baseline, the mean IPSS-I decreased from a baseline score of 6.8–4.9 at 3 years post-SBRT. This decrease was both statistically (p < 0.0001) and clinically significant (minimally important difference = 1.45). Only 14.6% of patients felt that urinary frequency was a moderate to big problem at 3 years post-SBRT (p = 0.23).Conclusion: Treatment of prostate cancer with SBRT resulted in an acute increase in irritative urinary symptoms that peaked within the first month post-treatment. Irritative voiding symptoms returned to baseline in the majority of patients by 3 months post-SBRT and were actually improved from baseline at 3 years post-SBRT.

Comparing Patient-Reported Outcomes in Patients With and Without Late Urinary Flare Following Stereotactic Body Radiation Therapy (SBRT) for Localized Prostate Cancer

Stereotactic body radiation therapy (SBRT) is a newer treatment option for clinically localized prostate cancer. Late urinary symptom flare occurs transiently in a minority of patients 6 to 18 months following completion of treatment. Here, we compare patient-reported outcomes among patients with and without late urinary symptom flare following SBRT. At an academic medical center, 216 patients were treated for localized prostate cancer using the SBRT monotherapy protocol from June 2008-May 2010. Treatment was delivered using robotic SBRT at doses of 35-36.25 Gy in 5 fractions. Late urinary symptom flare was defined as an American Urological Association (AUA) symptom score ≥ 15 with an increase of ≥ 5 points above baseline six months after the completion of SBRT. Patient-reported outcomes and alpha-antagonist usage were assessed pretreatment at each follow-up visit. Patient-reported urinary symptoms were measured using the Expanded Prostate Cancer Index Composite (EPIC) short form. Of the 216 patients treated, 29 met criteria for late urinary symptom flare. Among patients with flare, the median age was 66 years (range 48-77) compared to 70 (range 49-90) for those without flare (p = 0.007). Use of alpha-antagonists was more common in patients without flare during the first 6 months following treatment, but was more common in patients with flare at and beyond 9 months. Among all patients, AUA symptom scores spiked transiently at 1 month post-treatment; a second transient increase was observed only among flare patients at 12 months. The EPIC urinary incontinence, irritative/obstructive, and bother domain scores declined at 1 month for all patients. Among flare patients only, a second transient nadir in these domains was observed at 12 months before returning to baseline at 24 months. Differences in patient-reported quality-of-life outcomes are observed between patients with and without late urinary symptom flare following SBRT. Specifically, declines in quality of life domains appear to parallel increases in urinary symptom scores among patients with flare. Notably, early toxicity does not appear to predict late toxicity in our cohort. Younger age appears to be a predictive factor associated with flare. Further studies are needed to determine which treatment variables confer greater risk of late urinary symptom flare.

Clinical characteristics and management of late urinary symptom flare following stereotactic body radiation therapy for prostate cancer.

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.

Urinary obstruction following stereotactic body radiation therapy (SBRT) for clinically localized prostate cancer.

196 Background: Obstructive urinary symptoms are common following prostate cancer treatment with radiation therapy. Given the higher dose of radiation per fraction using stereotactic body radiation therapy (SBRT) there is concern that post-SBRT obstructive urinary symptoms would be more severe. This study sought to evaluate obstructive urinary symptoms and urinary retention requiring catheterization following SBRT for prostate cancer. Methods: Patients treated with SBRT monotherapy for localized prostate cancer from August 2007 to July 2011 at Georgetown University Hospital with a minimum of two years of follow-up were included in this study. Treatment was delivered using the CyberKnife with doses of 35 Gy to 36.25 Gy in five fractions. Urinary retention was recorded and scored using the CTCAE v.4. Patient-reported urinary symptoms were assessed using the International Prostate Symptom Score (IPSS) before treatment and at months 1, 3, 6, 9, and 12 and every six months thereafter. Results: Two hundred sixty nine patients at a median age of 69 received SBRT with a median follow-up of three years. Prior to treatment, 32.1% of patients utilized alpha-antagonists and 17.8% were dissatisfied with their urinary function. The two-year actuarial incidence rates of acute and late urinary retention greater than or equal to grade 2 were 39.5% and 41.4%. Alpha-antagonist utilization rose at one month (57.9%) and 18 months (48.0%) post-treatment. However, grade 3 urinary retention was low with four men (1.5%) requiring catheterization and/or transurethral resection of the prostate. A mean baseline IPSS obstructive symptom score of 3.6 significantly increased to 5.0 at one month (p &lt; 0.0001), however returned to baseline at three months (p = 0.74). Late IPSS increases were common, but transient. The IPSS obstructive symptom score returned to baseline in 79.6% of patients by six months and 92.6% by two years. Dissatisfaction with urinary function declined to 14% by two years post treatment (p &lt; 0.05). Conclusions: Treatment of prostate cancer with SBRT resulted in an acute increase in obstructive urinary symptoms, which peaked at one month post-treatment. However, the risk of acute urinary retention requiring catheterization was low. Obstructive urinary symptoms returned to baseline in the majority of patients by six months and in more than 90% by two years.

Clinical characteristics and management of late symptom flare following stereotactic body radiation therapy for clinically localized prostate cancer.

194 Background: Stereotactic body radiation therapy (SBRT) is increasingly utilized as primary treatment for clinically localized prostate cancer. While acute urinary symptoms are well recognized, late toxicities of SBRT have not been fully described. Here, we characterize the clinical features of late symptom flare and describe symptom management approaches. Methods: Two hudred sixteen patients with clinically localized prostate cancer were treated with SBRT between February 2008 and January 2011 at Georgetown University Hospital. Twenty-nine patients who experienced late-symptom flare were included in this retrospective analysis. Treatment was delivered using the CyberKnife (35 Gy to 36.25 Gy in five fractions). Prevalence of urinary toxicities was determined using CTCAE v.4. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA) and the Expanded Prostate Cancer Index Composite (EPIC) short form. Results: Median age was 66 with 55% being of African descent. Late grade 2 frequency/urgency peaked at 12 months (17.2%), then returned to baseline at 18 months. Late grade 2 retention peaked at 18 months (65.5%), then returned to baseline at 24 months. Late grade greater than or equal to 1 dysuria peaked at nine months (25.0%), then returned to baseline at 24 months. Alpha-antagonist usage peaked at 18 months (85%) then decreased at 24 months. At 12 months, 21% required anti-inflammatories and/or urethral analgesics. Median AUA score rose from a baseline of 6 to 15 at 12 months, then returned to baseline by 24 months. EPIC urinary function and bother scores dropped to a nadir at 9 to 12 months post-treatment, then returned to baseline at 24 months. Conclusions: Symptom flare is a late syndrome consisting of various degrees of urinary frequency/urgency, retention and dysuria. It occurs approximately one year following SBRT, resolves spontaneously, and urinary function returns to baseline by two years. Early identification and initiation of conservative symptomatic management may decrease the need for invasive interventions. Anticipatory counseling prior to treatment may limit bother due to these transient urinary symptoms.

Patient-reported genitourinary toxicity for long-term prostate cancer survivors treated with radiation therapy

Background:The objective of this study is to provide comprehensive overviews of patient-reported urinary symptoms for long-term prostate cancer survivors treated with radiation therapy and for untreated, healthy men.Methods:We performed a population-based cross-sectional study using a study-specific postal questionnaire assessing symptoms among 1007 men consecutively treated at the Sahlgrenska University Hospital, Göteborg, Sweden from 1993–2006 (primary or salvage external beam radiation therapy (EBRT) or EBRT and high-dose rate brachytherapy). We also randomly recruited 350 non-pelvic-irradiated matched control men from the Swedish Total Population Register. Symptom prevalence and prevalence ratios were computed.Results:Survey participation rate was 89% (874/985) for eligible survivors and 73% (243/332) for eligible controls. Median time from treatment to follow-up was 5 years (range, 1–14 years). Among the 21 investigated symptoms reflecting obstruction, frequency, urgency, pain and incontinence, we found significantly higher prevalence compared with controls for 9 symptoms in the EBRT group, 10 in the EBRT+brachytherapy group and 5 in the salvage EBRT group. The prevalence for a majority of the symptoms was stable over time.Conclusion:The presented toxicity profiles provide a thorough understanding of patient-reported urinary symptoms that can assist in developing personalised therapy for prostate cancer.

Stereotactic body radiation therapy (SBRT) following procedures for benign prostatic hyperplasia (BPH): A report on early toxicity.

165 Background: When treating patients with prostate cancer, hypofractionation with SBRT takes advantage of radiobiologically favorable factors as compared to conventional fractionation. However, this may increase the risk of urinary toxicity, especially in patients with prior procedures for BPH. Herein, we report early urinary toxicity following SBRT in patients with a history of procedures for BPH. Methods: Thirty three patients treated with SBRT for localized prostate cancer from February 2009 to October 2011 at Georgetown University Hospital with history of a prior procedure for BPH were included in this retrospective analysis. Treatment was delivered using the CyberKnife with doses of 35 Gy-36.25 Gy in 5 fractions. Toxicities were scored using the CTCAE v.3. Cystoscopy findings were retrospectively reviewed. Patient-reported urinary symptoms were assessed using the American Urological Association Symptom Score (AUA). Results: The median age was 70 years (range, 64 - 84). The median follow-up time was 18.7 months (range 9.2 – 38.9). Grade 2 or 3 urinary toxicity occurred in 9 patients and there were no grade 4 or 5 toxicities. Hematuria occurred in 12 patients. The median time to onset of hematuria from SBRT was 6 months (range 1 – 30). Grade 1 hematuria occurred in 7 patients, grade 2 in 4 patients and 1 patient experienced grade 3. Cystoscopy was performed in 9 of these patients at a median time of 9 months (range 3-27). Eight had hyperemia or evidence of bleeding from the prostatic urethra and 5 of these patients also had evidence of bleeding from the bladder neck/wall. All patients except one, who died from other causes, are still being followed and hematuria has resolved in 9 of the 12 patients. The median baseline AUA symptom score of 7 increased to 11 at 1 month, however decreased to a median score of 6 at 3 months. The median AUA symptom score increased to 9 at 1 year. Conclusions: A history of prior transurethral resection of prostate may predispose patients to increased urinary toxicity and hematuria following prostate SBRT. Stricter urethra/bladder neck dosimetric criteria or alternative fractionation regimens may be required to decrease urinary toxicity in these patients.

Improving initial management of lower urinary tract symptoms in primary care: Costs and patient outcomes

Guidelines for primary care management of lower urinary tract symptoms in older men recommend shared decision making regarding the choice of treatment. In this study we aimed to determine the costs and patient outcomes of an implementation strategy designed to enhance uptake of these guidelines. The intervention comprised a distance learning programme for general practitioners, comprising evidence-based information, assessment of learning needs, a knowledge test and patient education materials. The control group only received the written guidelines. A cluster randomized trial in 187 older male patients compared costs and outcomes in the two study groups. A healthcare perspective was taken in the economic evaluation, with a 3-month time horizon. The primary health outcome was patient-reported urinary symptoms at 3 months. Costs relating to the distance learning package and the healthcare provided were considered, using undiscounted standardized prices. Patient-reported urinary symptoms at 3 months did not differ between the study groups: 66% and 61% with moderate symptoms and 7% and 11% with severe symptoms in the intervention and control groups, respectively. The mean total costs per patient were euro28.15 lower in the intervention group (euro93.11) compared to the control group (euro121.26), mainly because of a lower number of referrals to the urologist. A bootstrap analysis showed an incremental cost-effectiveness ratio of euro111.98 (95% CI -euro423 to +euro329). The distance learning programme did not change health outcomes, but it reduced costs in the first 3 months after an initial consultation compared to written guidelines. Studies with a longer follow-up period are needed.