International Prostate Symptom Score Increase Research Articles

Dose-Volume Parameters to the Urinary Tract Sub-Volumes and Predictors of Genitourinary Acute Toxicity in a Phase 2 Clinical Trial Assessing MRI-Guided Prostate Boost for Localized Prostate Cancer - The Miami BlastM Trial.

The relationship between radiotherapy dose to the sub-volumes of the genitourinary (GU) tract and GU toxicity is poorly understood, particularly in prostate cancer patients treated with an intraprostatic dominant lesion (IDL) boost. While the use of IDL boost improves outcomes, it results in higher doses to GU structures and potentially increased toxicity. We investigated the association between dose-volume histogram (DVH) parameters for urinary tract sub-volumes and GU toxicity in the context of IDL boost in patients enrolled in the Miami BlastM Trial. DVH data were assessed for patients enrolled in the Miami BlastM, a randomized phase 2 trial (NCT20140627) evaluating upfront versus integrated IDL boost. IDL GTV boost consisted of either 12-14 Gy administered on day 1 or integrated boost of 2.4 Gy per fraction (91.2 Gy total, 98.5 Gy 2.0 Equiv), with the prostate receiving 76 Gy in 38 fractions. Bladder trigone (BTg) and urethra sub-volumes were contoured retrospectively on planning CT scans. GU toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE) version 4 and International Prostate Symptom Score (IPSS). DVHs of the bladder, BTg, bladder minus BTg, prostatic urethra, and bulbomembranous urethra were examined. The primary composite endpoint was CTCAE GU acute toxicity grade (G) ≥2 and/or IPSS increase of ≥10 from baseline. Secondary endpoints were GU acute toxicity G≥2, GU late toxicity G≥2, and IPSS increase of ≥10 from baseline. Univariable and multivariable logistic regression analyses were performed. A total of 129 patients treated between February 2015 and January 2022 were eligible for analysis. One hundred and one (78%) patients developed either GU acute toxicity G≥2 (68%) and/or an IPSS increase of ≥10 from baseline (30%). Less than 2% of patients developed GU toxicity G≥3. BTg V30 Gy was significantly associated with IPSS increase ≥10 (p = 0.046). The bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and GU late toxicity G≥2 (p <0.05 for both). Average maximum and mean urethral doses were 88.9 and 81.5 Gy, respectively. The BTg maximum dose, V20 Gy, V30 Gy, and V40 Gy were not significantly associated with the primary composite endpoint (p = 0.56, 0.75, 0.89, 0.82, respectively). On multivariable analysis, a higher bulbomembranous urethral maximum dose was significantly associated with GU acute toxicity G≥2 and/or IPSS increase of ≥10 from baseline (p = 0.019). Our data suggest a dose-effect relationship between maximum doses to the bulbomembranous urethra and GU toxicity. A better understanding of RT-related changes to specific sub-volumes of the urethra and strategies to mitigate urethral dose could enhance the therapeutic ratio in prostate cancer patients treated with MRI-guided IDL boost.

Smoking and lower urinary tract symptoms in Reduction by Dutasteride of Prostate Cancer EventsTrial.

Benign prostatic hyperplasia is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Smoking has many well-established adverse effects, but its effects on benign prostatic hypertrophy(BPH) and associated LUTS are unclear. We sought to determine if smoking is a risk factor for the incidence of LUTS in asymptomatic men and for the progression of LUTS in symptomatic men. We performed a post-hoc analysis of Reduction by Dutasteride of Prostate Cancer Events in 3060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) < 8 and in 2198 symptomatic men with baseline IPSS ≥ 8 not taking 5α-reductase inhibitors or α-blockers. We used multivariable Cox regression models to assess associations between smoking status at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical or surgical treatment for BPH, or sustained clinically significant LUTS (two reports of IPSS > 14). Among symptomatic men, LUTS progression was defined as IPSS increase of ≥4 points from baseline, surgical intervention for BPH, or starting a new BPH drug. Of 3060 asymptomatic men, 15% (n = 467) were current, 40% (n = 1231) former, and 45% (n = 1362) never-smokers. Of 2198 symptomatic men, 14% (n = 320) were current, 39% (n = 850) former, and 47% (n = 1028) never-smokers. In asymptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with LUTS incidence (adjusted hazard ratio [adj-HR] = 1.08; 95% confidence interval [95%CI]: 0.78-1.48 and adj-HR = 1.01; 95% CI: 0.80-1.30). In symptomatic men, compared with never-smokers, current and former smoking at baseline were not associated with the progression of LUTS (adj-HR = 1.11; 95% CI: 0.92-1.33 and adj-HR = 1.03; 95% CI: 0.90-1.18). In REDUCE, smoking status was not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men.

PD02-06 SERUM TESTOSTERONE AND DIHYDROTESTOSTERONE AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS IN REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS TRIAL

You have accessJournal of UrologyCME1 Apr 2023PD02-06 SERUM TESTOSTERONE AND DIHYDROTESTOSTERONE AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS IN REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS TRIAL James Daniels, James Mirocha, Daniel Moreira, Gerald Andriole, and Stephen Freedland James DanielsJames Daniels More articles by this author , James MirochaJames Mirocha More articles by this author , Daniel MoreiraDaniel Moreira More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , and Stephen FreedlandStephen Freedland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Though the pathogenesis of BPH is unclear, it was previously believed that increasing androgen levels had a role, though not all data support this idea. We tested if elevated serum testosterone and elevated serum DHT are risk factors for LUTS incidence in asymptomatic men and for LUTS progression in symptomatic men. METHODS: A post-hoc analysis of REDUCE was carried out in 3009 asymptomatic men with baseline International Prostate Symptom Score (IPSS) <8 and in 2145 symptomatic men with baseline IPSS≥8 not taking α-blockers or 5α-reductase inhibitor medications. The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial was a randomized trial of dutasteride for prostate cancer prevention in men with an elevated PSA and negative pre-study biopsy. IPSS was measured every 6 months over the 4-year study. We estimated multivariable adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) using Cox models to test the association between quintiles of serum testosterone and quintiles of serum dihydrotestosterone (DHT) at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical treatment, surgery or sustained clinically significant LUTS (i.e., 2 reports of IPSS>14). Among symptomatic men, LUTS progression was defined as an IPSS increase of ≥4 points from baseline, any surgical procedure for BPH, or the start of a new BPH medication. RESULTS: In asymptomatic men, relative to the lowest quantile, all quintiles of serum testosterone and all quintiles of DHT were unrelated to LUTS incidence (all p≥0.25). In symptomatic men, relative to the lowest quantile, all quintiles of serum testosterone and all quintiles of DHT were unrelated to LUTS progression (all p≥0.17). There was no significant interaction between treatment with dutasteride and serum testosterone or DHT when predicting LUTS; as such, data were not stratified by treatment assignment. CONCLUSIONS: In the REDUCE study, higher serum testosterone and higher serum DHT were not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men. These data do not support the hypothesis that serum androgen levels in middle-aged men are associated with LUTS. Source of Funding: Dr. Daniels is funded by the NIH grants TL1 DK132768 and U2C DK129496 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e71 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information James Daniels More articles by this author James Mirocha More articles by this author Daniel Moreira More articles by this author Gerald Andriole More articles by this author Stephen Freedland More articles by this author Expand All Advertisement PDF downloadLoading ...

Magnetic Resonance Imaging–Guided vs Computed Tomography–Guided Stereotactic Body Radiotherapy for Prostate Cancer

Magnetic resonance imaging (MRI) guidance offers multiple theoretical advantages in the context of stereotactic body radiotherapy (SBRT) for prostate cancer. However, to our knowledge, these advantages have yet to be demonstrated in a randomized clinical trial. To determine whether aggressive margin reduction with MRI guidance significantly reduces acute grade 2 or greater genitourinary (GU) toxic effects after prostate SBRT compared with computed tomography (CT) guidance. This phase 3 randomized clinical trial (MRI-Guided Stereotactic Body Radiotherapy for Prostate Cancer [MIRAGE]) enrolled men aged 18 years or older who were receiving SBRT for clinically localized prostate adenocarcinoma at a single center between May 5, 2020, and October 1, 2021. Data were analyzed from January 15, 2021, through May 15, 2022. All patients had 3 months or more of follow-up. Patients were randomized 1:1 to SBRT with CT guidance (control arm) or MRI guidance. Planning margins of 4 mm (CT arm) and 2 mm (MRI arm) were used to deliver 40 Gy in 5 fractions. The primary end point was the incidence of acute (≤90 days after SBRT) grade 2 or greater GU toxic effects (using Common Terminology Criteria for Adverse Events, version 4.03 [CTCAE v4.03]). Secondary outcomes included CTCAE v4.03-based gastrointestinal toxic effects and International Prostate Symptom Score (IPSS)-based and Expanded Prostate Cancer Index Composite-26 (EPIC-26)-based outcomes. Between May 2020 and October 2021, 156 patients were randomized: 77 to CT (median age, 71 years [IQR, 67-77 years]) and 79 to MRI (median age, 71 years [IQR, 68-75 years]). A prespecified interim futility analysis conducted after 100 patients reached 90 or more days after SBRT was performed October 1, 2021, with the sample size reestimated to 154 patients. Thus, the trial was closed to accrual early. The incidence of acute grade 2 or greater GU toxic effects was significantly lower with MRI vs CT guidance (24.4% [95% CI, 15.4%-35.4%] vs 43.4% [95% CI, 32.1%-55.3%]; P = .01), as was the incidence of acute grade 2 or greater gastrointestinal toxic effects (0.0% [95% CI, 0.0%-4.6%] vs 10.5% [95% CI, 4.7%-19.7%]; P = .003). Magnetic resonance imaging guidance was associated with a significantly smaller percentage of patients with a 15-point or greater increase in IPSS at 1 month (6.8% [5 of 72] vs 19.4% [14 of 74]; P = .01) and a significantly reduced percentage of patients with a clinically significant (≥12-point) decrease in EPIC-26 bowel scores (25.0% [17 of 68] vs 50.0% [34 of 68]; P = .001) at 1 month. In this randomized clinical trial, compared with CT-guidance, MRI-guided SBRT significantly reduced both moderate acute physician-scored toxic effects and decrements in patient-reported quality of life. Longer-term follow-up will confirm whether these notable benefits persist. ClinicalTrials.gov Identifier: NCT04384770.

Dose to the Bladder Trigone and Acute Urinary Toxicity after Prostate SBRT in a Randomized Phase 3 Trial

<h3>Purpose/Objective(s)</h3> The bladder trigone is physiologically the most densely innervated region of the bladder, owing to its prominent role in detrusor overactivity. Radiotherapy (RT) dose to the bladder trigone has been previously associated with increased genitourinary (GU) toxicity in prostate cancer patients treated with conventionally fractionated RT. However, there is little data exploring dosimetric parameters to the bladder trigone after prostate stereotactic body radiotherapy (SBRT). Herein, we assessed the potential association of bladder trigone dose-volume parameters and acute GU toxicity in prostate cancer patients treated with SBRT in a phase 3 clinical trial. <h3>Materials/Methods</h3> We included patients treated with prostate SBRT in an ongoing international, prospective randomized phase 3 trial (NCT01794403) between April 2013 and January 2022. Patients received 36.25 Gy to the prostate and proximal seminal vesicles, in 5 fractions, 3x week. The bladder trigone volumes were contoured retrospectively. GU toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE Version 4.0) and International Prostate Symptom Score (IPSS). Dose-volume histograms of the urethra, whole bladder, bladder trigone, and bladder minus trigone were examined. The primary endpoint was physician-reported CTCAE GU acute toxicity ≥2 and/or patient-reported IPSS increase of ≥10 from baseline within 3 months from treatment. Univariate and multivariate analyses were performed via logistic regression models. <h3>Results</h3> A total of 56 patients were eligible for analysis. Twenty-nine patients developed GU acute toxicity ≥2 and/or an IPSS increase of ≥10 within three months from starting treatment. The bladder trigone maximal dose, V20, V30, and V40 (p=0.475, 0.228, 0.155, 0.115, respectively) were not significantly associated with GU acute toxicity ≥2 and/or IPSS increase of ≥10 on univariate analysis. However, the maximal dose to the bladder trigone showed a trend towards a statistically significant association with an IPSS increase ≥10 (p=0.052). The urethra mean dose, V20, V25, and V30 (p=0.041, 0.020, 0.019, 0.021, respectively) were significantly associated with GU acute toxicity ≥2 and/or IPSS increase of ≥10 on univariate analysis. On multivariate analysis, the urethra V25 (p=0.024) was significantly associated with GU acute toxicity ≥2 and/or IPSS increase of ≥10. <h3>Conclusion</h3> In an ongoing phase 3 clinical trial assessing prostate SBRT, we confirm previously reported relationships of urethral dose and GU toxicity. There is also a trend in the association of maximal dose to the bladder trigone with patient-reported outcomes, suggesting that attention should be paid to this subvolume. Further investigation in larger studies on the dosimetric impact to urinary tract subvolumes in prostate SBRT is warranted.

De Novo or Increasing Lower Urinary Tract Symptoms during COVID-19 Infection: Long-term Results

Background: How COVID-19 affects lower urinary tract symptoms (LUTS) in men has not been demonstrated by published research. This study examined the de novo development of LUTS and the change in the severity of pre-existing LUTS in men hospitalized with COVID-19. A follow-up period of 12 months after COVID-19 infection provided data on the long-term effect of COVID-19 vs. LUTS. Methods: Data were collected from 70 male patients diagnosed with COVID-19 via nasopharyngeal swab RT-PCR technology between June 2020 and April 2021. The patient’s age, comorbidities, date of COVID-19 diagnosis, date of LUTS, International Prostate Symptom Score (IPSS), prostate-specific antigen (PSA), creatinine, and D-dimer levels, urinalysis, urine culture and duration of hospital stay were recorded. Statistical analyses were conducted to compare between pre-COVID and post-COVID IPSS and other data. Results: 42 patients were included in this study with a, mean age of patients were 54.76 ± 11.95 years. In 8 patients there was no change in IPSS pre- vs. post-COVID. In the remaining 34 patients (80.9%), the median IPSS increased from a pre-COVID value of 2 to 10 during COVID (p &lt; 0.001). In the subgroup analysis based on age &lt;50 years vs. ≥50 years, statistically significant increase in IPSS were found in both age groups pre- and post-COVID. Conclusions: In male patients of all ages, COVID-19 results in the de novo occurrence of LUTS and an increase in pre-existing LUTS in approximately 80% of patients. These symptoms were found to persist at a 12-months follow-up.

Long-term outcomes of Holmium laser enucleation of prostate and predictive model for symptom recurrence.

Holmium laser enucleation of prostate (HoLEP) represents one of the most studied surgical techniques for benign prostatic hyperplasia (BPH). Its efficacy in symptom relief has been widely depicted. However, few evidence is available regarding the possible predictors of symptom recurrence. We aimed to evaluate long-term outcomes, symptom recurrence rate, and predictors in patients that underwent HoLEP. We retrospectively analyzed data from patients that consecutively underwent HoLEP for BPH from 2012 to 2015 at two tertiary referral centers. Functional outcomes were evaluated by uroflowmetry parameters and International Prostate Symptom Score (IPSS) questionnaire administration at follow-up visits at 12, 24, and 60 months. The primary outcome was the symptomatic patients' rate presenting lower urinary tract symptoms (LUTS) after 60 months from surgery, defined as in case of one or more of the following: IPSS more than 7, post voidal residue (PVR) more than 20 ml, need for medical therapy for LUTS or redo surgery for bladder outlet obstruction. Multivariable logistic regression analyses evaluated predictors for being symptomatic at follow-up. Covariates consisted of: preoperative peak flow rate (PFR), PVR, and IPSS, prostate volume, age (all as continuous), and surgical technique. A total of 567 patients were available for our analyses. Median prostate volume was 80cc, with a median PFR of 8 ml/s and median PVR of 100cc. One hundred and twenty-five (22%) patients were found to be symptomatic at follow-up. Redo surgery was needed for 25 (4.4%) patients. After adjusting for possible confounders, an increase in preoperative PVR (odds ratio [OR] 1.005) and IPSS (OR 1.12) resulted as independent predictors for symptom recurrence (all p < 0.001). HoLEP can provide durable symptom relief regardless of the chosen technique. Patients with an important preoperative symptom burden or a high PVR should be carefully counseled on the risk of symptom recurrence.

Statin Use and Lower Urinary Tract Symptoms Incidence and Progression in Reduction by Dutasteride of Prostate Cancer Events (REDUCE) Trial.

Benign prostatic hyperplasia (BPH) is a common disease often manifested by lower urinary tract symptoms (LUTS). We previously found statins were associated with modest attenuations in prostate growth over time in REDUCE. We tested whether statins were associated with LUTS incidence in asymptomatic men and LUTS progression in symptomatic men. We performed a post-hoc analysis of REDUCE in 3,060 "asymptomatic" men with baseline International Prostate Symptom Score (IPSS) <8 and in 2,198 symptomatic men with baseline IPSS ≥8 not taking α-blockers or 5α-reductase inhibitors. We used multivariable Cox regression models to assess associations between statin use at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first reported medical or surgical treatment for BPH or sustained clinically significant LUTS (2 reports of IPSS >14). Among symptomatic men, LUTS progression was defined as IPSS increase ≥4 points from baseline, any surgical procedure for BPH, or initiation of a BPH drug. Among asymptomatic and symptomatic men, 550 (18%) and 392 (18%) used statins at baseline, respectively. On multivariable analysis, statin use was not associated with LUTS incidence (HR 1.05; 95% CI 0.78-1.41, p=0.74) in asymptomatic men, or with LUTS progression (HR 1.13; 95% CI 0.96-1.33, p=0.15) in symptomatic men. Similar results were seen in the dutasteride and placebo arms when stratified by treatment assignment. In REDUCE, statin use was not associated with either incident LUTS in asymptomatic men or LUTS progression in symptomatic men. These data do not support a role for statins in LUTS prevention or management.

MP28-08 SMOKING AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS (LUTS) IN THE REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS (REDUCE) TRIAL

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology & Evaluation (MP28)1 Sep 2021MP28-08 SMOKING AND INCIDENCE AND PROGRESSION OF LOWER URINARY TRACT SYMPTOMS (LUTS) IN THE REDUCTION BY DUTASTERIDE OF PROSTATE CANCER EVENTS (REDUCE) TRIAL Jordan J. Kramer, Illona Csizmadi, Lin Gu, Daniel Moreira, Gerald Andriole, and Stephen J. Freedland Jordan J. KramerJordan J. Kramer More articles by this author , Illona CsizmadiIllona Csizmadi More articles by this author , Lin GuLin Gu More articles by this author , Daniel MoreiraDaniel Moreira More articles by this author , Gerald AndrioleGerald Andriole More articles by this author , and Stephen J. FreedlandStephen J. Freedland More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002025.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign prostatic hyperplasia (BPH) is common in older men, with many developing lower urinary tract symptoms (LUTS) that impair quality of life. Smoking has many well-established adverse effects, but its effects on BPH and associated LUTS are unclear. We sought to determine if smoking is a risk factor for the incidence of LUTS in asymptomatic men and for the progression of LUTS in symptomatic men. METHODS: A post-hoc analysis of REDUCE was carried out in 3060 asymptomatic/minimally symptomatic (aka “asymptomatic”) men with baseline International Prostate Symptom Score (IPSS) <8 and in 2198 symptomatic men with baseline IPSS ≥8 not taking α-blockers or 5α-reductase inhibitor medications. We estimated multivariable adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) using Cox proportional hazard models to assess the association between smoking at baseline and LUTS incidence and progression. Among asymptomatic men, incident LUTS was defined as the first report of medical treatment, surgery or sustained clinically significant LUTS (i.e. 2 reports of IPSS>14). Among symptomatic men, LUTS progression was defined as an IPSS increase of ≥4 points from baseline, any surgical procedure for BPH, or the start of a new BPH drug. RESULTS: Of 3060 asymptomatic men, 15% (n=467) were current, 40% (n=1231) former and 45% (n=1362) never-smokers. Of 2198 symptomatic men, 14% (n=320) were current, 39% (n=850) former and 47% (n=1028) never-smokers. In asymptomatic men, compared with never-smokers, current and former smoking at baseline was not associated with LUTS incidence (adj-HR=1.08; 95% CI: 0.78-1.48 and adj-HR=1.01; 95% CI: 0.80-1.30, for current and former smoking status, respectively). In symptomatic men, compared with never-smokers, current and former smoking at baseline was not associated with the progression of LUTS (adj-HR=1.11; 95% CI: 0.92-1.33 and adj-HR=1.03; 95% CI: 0.90-1.18, for current and former smoking status, respectively). Similar results were seen in dutasteride and placebo arms in data stratified by treatment assignment. CONCLUSIONS: In the REDUCE study, smoking status was not associated with either incident LUTS in asymptomatic men or progression of LUTS in symptomatic men. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e483-e484 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jordan J. Kramer More articles by this author Illona Csizmadi More articles by this author Lin Gu More articles by this author Daniel Moreira More articles by this author Gerald Andriole More articles by this author Stephen J. Freedland More articles by this author Expand All Advertisement Loading ...

Study of heart rate variability in benign prostatic hyperplasia - A hospital-based study

Background: Benign prostatic hyperplasia (BPH) is a major disease affecting middle-aged and elderly male. BPH is the result of unregulated proliferation of connective tissue, smooth muscle, and glandular epithelium within the prostatic zone resulting in lower urinary tract symptoms. The exact etiopathogenesis of BPH remains ambiguous, but there is increasing evidence that sympathetic overactivity appears to have an important role in the pathogenesis of BPH. Undoubtedly, the constellations of cellular, pathologic processes that give rise to symptoms of BPH are far complex than we currently realize. Only by unraveling these complexities, we will be able to successfully design alternative strategies to treat and prevent the adverse impact of BPH. Aims and Objectives: This study aims to evaluate the role of autonomic nervous system in the pathogenesis of BPH. Materials and Methods: After taking clearance from the ethical committee, a total of 42 male patients who were diagnosed clinically and ultrasonologically as cases of BPH were included in the study after applying appropriate inclusion and exclusion criteria. Patients were scored for the International Prostate Symptom Score (IPSS). The basal recording of electrocardiogram in lead II was done for 5 min. The Polyrite D was used for heart rate variability by frequency domain method. Pearson’s correlation coefficient was calculated for low frequency (LF) versus IPSS and LF versus prostate size. Results: LF component was found significantly high in BPH patients. R value for LF versus IPSS was 0.9558 showing an increase in a sympathetic component with increase in IPSS which is statistically significant (P < 0.001). Patients with higher LF value had more lower urinary tract symptoms. R value for LF versus prostate size was 0.9421 which is also statistically significant (P < 0.001). This means if there is increase in the prostate size sympathetic activity also increased. Conclusion: This study was done with an aim to recommend methods of primordial prevention and our study shows greater sympathetic activity in BPH patients. Hence, we suggest yogic interventions such as meditation for primordial prevention.

Reductions in prostatic doses are associated with less acute morbidity in patients undergoing Pd-103 brachytherapy: Substantiation of the rationale for focal therapy

PurposeInterest in prostate dose reduction or focal treatment exists due to expected reductions in treatment morbidity. Prior analyses have not generally corroborated relationships between prostate or urethral dose and urinary toxicity after brachytherapy, but such analyses have been performed on cohorts all receiving the same prescribed dose. We analyzed patients treated to differing prescription doses to assess acute urinary morbidity with dose reduction. Methods and MaterialsPatients treated with Pd-103 to either 125 Gy or 90–100 Gy were compared using the International Prostate Symptom Score (IPSS) at 1-month postimplant. Patients in the 90–100 Gy cohort began external beam radiation therapy after their 1-month assessment; thus, toxicities were measured before contribution from external beam radiation therapy. Patient/treatment characteristics were compared to verify subgroup homogeneity. Dose and change in IPSS 1 month after treatment were assessed using a multivariate linear regression model. ResultsOne hundred ninety-one and 41 patients were treated with 125 Gy versus 90–100 Gy, respectively. Preimplant and postimplant prostate volumes and initial IPSS were similar between groups. Higher prescription dose and increased pretreatment IPSS were independent predictors of increased 1-month IPSS. In addition, every 10 percentage point additional prostate volume receiving a given dose was associated with increase in IPSS after treatment for the same level of pretreatment IPSS. ConclusionLower prescription dose and decreased volume of high-dose regions to the prostate correlated with reduced acute urinary morbidity after brachytherapy. Our findings suggest that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy.

Assessment of lower urinary symptom flare with overactive bladder symptom score and International Prostate Symptom Score in patients treated with iodine-125 implant brachytherapy: long-term follow-up experience at a single institute

BackgroundThe aim of this study was to evaluate the combined use of the overactive bladder symptom score (OABSS) and International Prostate Symptom Score (IPSS) as an assessment tool for urinary symptom flare after iodine-125 (125I) implant brachytherapy. The association between urinary symptom flare and prostate-specific antigen (PSA) bounce was investigated.MethodsChanges in the IPSS and OABSS were prospectively recorded in 355 patients who underwent seed implantation. The percentage distribution of patients according to the difference between the flare peak and post-implant nadir was plotted to define significant increases in the scores. The clinicopathologic characteristics, treatment parameters, and post-implant dosimetric parameters were compared between the non-flare and flare groups. PSA bounce was defined as an elevation of ≥0.1 ng/mL or ≥0.4 ng/mL compared to the previous lowest value, followed by a decrease to a level at or below the pre-bounce value.ResultsA clinically significant increase required an IPSS increase of at least 12 points and an OABSS increase of at least 6 points based on a time-course analysis of total scores and the QOL index. Assessment only by IPSS failed to detect 40 patients (11%) who had urinary symptom flare according to the OABSS. Univariate and multivariate analyses revealed that patients treated with higher biologically effective doses and those without diabetes mellitus had higher risks of urinary flare. There was no statistical correlation between the incidence and time of urinary symptom flare onset and that of a PSA bounce.ConclusionsTo our knowledge, this is the first report to prove the clinical potential of the OABSS as an assessment tool for urinary symptom flare after seed implantation. Our findings showed that persistent lower urinary tract symptoms after seed implantation were attributed to storage rather than to voiding issues. We believe that assessment with the OABSS combined with the IPSS would aid in decision-making in terms of timing, selection of a treatment intervention, and assessment of the outcome.

Long Term Patient Reported Urinary Function Following External Beam Radiotherapy for Prostate Cancer

IntroductionThis study reports long-term patient reported urinary function and urinary-related quality of life (uQoL) after external beam radiotherapy (EBRT) for localized prostate cancer. Methods574 men underwent definitive prostate EBRT to 70–78 Gy±androgen deprivation therapy between 2000 and 2009. The median follow-up from EBRT was 44 months. Patients were evaluated at baseline (pre-EBRT) and at intervals post-treatment using the International Prostate Symptom Score (IPSS) instrument. ResultsPatients with mild IPSS at baseline (total 0–7) reported median total scores of 3, 4 and 3 at baseline, 6 and 48 months respectively post-EBRT. For patients with moderate IPSS at baseline (total 8–19), median total IPSS was 12 at baseline and 9 at both 6 and 48 months. For the severe IPSS group at baseline (total 20–35), the median total IPSS was 24, 12 and 14 at baseline, 6 and 48 months post-EBRT. The cumulative risk of persistent IPSS increase (greater than 5 points above baseline) at 48 months was 16%, 10% and 6% for patients with mild, moderate and severe baseline IPSS respectively. 94%, 54% and 11% of patients with mild, moderate and severe baseline IPSS reported good uQoL at baseline respectively, with these proportions increasing to 95%, 83% and 69% at 48 months. ConclusionUrinary symptoms and uQoL as measured by the IPSS instrument remained stable or improved for the majority of men after definitive EBRT with or without ADT for prostate cancer. This was especially notable for the group of men with worse baseline symptoms or uQoL, with risk of persistent worsening of urinary symptoms decreasing with higher baseline IPSS category. Understanding the expected pattern of urinary symptoms and related uQoL in the months and years following EBRT taking into account baseline urinary function is highly valuable for counselling men as part of the therapeutic decision-making process.

Modeling Urinary Dysfunction After External Beam Radiation Therapy of the Prostate Using Bladder Dose-Surface Maps: Evidence of Spatially Variable Response of the Bladder Surface

We assessed the association of the spatial distribution of dose to the bladder surface, described using dose-surface maps, with the risk of urinary dysfunction. The bladder dose-surface maps of 754 participants from the TROG 03.04-RADAR trial were generated from the volumetric data by virtually cutting the bladder at the sagittal slice, intersecting the bladder center-of-mass through to the bladder posterior and projecting the dose information on a 2-dimensional plane. Pixelwise dose comparisons were performed between patients with and without symptoms (dysuria, hematuria, incontinence, and an International Prostate Symptom Score increase of ≥10 [ΔIPSS10]). The results with and without permutation-based multiple-comparison adjustments are reported. The pixelwise multivariate analysis findings (peak-event model for dysuria, hematuria, and ΔIPSS10; event-count model for incontinence), with adjustments for clinical factors, are also reported. The associations of the spatially specific dose measures to urinary dysfunction were dependent on the presence of specific symptoms. The doses received by the anteroinferior and, to lesser extent, posterosuperior surface of the bladder had the strongest relationship with the incidence of dysuria, hematuria, and ΔIPSS10, both with and without adjustment for clinical factors. For the doses to the posteroinferior region corresponding to the area of the trigone, the only symptom with significance was incontinence. A spatially variable response of the bladder surface to the dose was found for symptoms of urinary dysfunction. Limiting the dose extending anteriorly might help reduce the risk of urinary dysfunction.

Reductions in Prostatic and Urethral Doses Are Associated With Less Acute Morbidity in Patients Undergoing Pd-103 Brachytherapy: Substantiation of the Rationale for Focal Therapy

Interest in prostate brachytherapy dose reduction or focal treatment exists due to expected reductions in treatment morbidity, but analyses in the modern era have not generally corroborated relationships between prostate or urethral dose and urinary toxicity. However, such analyses have been performed on cohorts receiving uniform prescribed doses. We analyzed patients treated to differing prescription doses to assess for effects of dose reduction on acute urinary morbidity, and to estimate the magnitude of such effects. An IRB-approved database was utilized. Patients treated with Pd-103 to either 125Gy or 90-100Gy were assessed using patient-reported International Prostate Symptom Score (IPSS) at 1-month post-implant, based on published evidence showing urinary morbidity after Pd-103 peaks at 1-month. Patients in 90-100Gy cohort received supplemental EBRT 45Gy after their 1-month assessment, thus toxicities were measured prior to any contribution from EBRT. Baseline patient characteristics were compared to verify subgroup homogeneity. Univariate and multivariate stepwise logistic regression analyses were performed to determine predictors of developing >10 point increase from baseline IPSS at 1 month. Post-implant catheterization rates were compared between groups. One hundred ninety-one patients and forty patients were treated with 125Gy vs 90-100Gy Pd-103, respectively. Treatment groups were similar with respect to pre-and post-implant prostate volumes, number of seeds used, and initial IPSS. Prostate and urethra doses were uniformly higher for the 125Gy group compared to the 90-100Gy group. Prescription dose, Initial IPSS, Prostate V150, V175 and V200Gy (absolute doses), Urethral V100Gy, D5, D10, D20, D30, and D50 (absolute doses) were all significantly associated with or trended toward significance vs IPSS >10 from baseline. The multivariate model demonstrated that Prescription dose, Initial IPSS, Urethral D30, and Prostate V150, V175 and V200Gy were independent predictors of developing >10 point increase from baseline IPSS scores at 1-month follow up. Patients in the 90-100 Gy cohort had median IPSS increase from baseline of 9.7 and 60% freedom from 10-point IPSS increase at 1-month, compared to 14.1 and 29% in the 125Gy cohort (P = 0.004 and <0.001, respectively). Post-implant catheterization occurred in 7.3% of the patients treated to 125Gy versus 0% in the 90-100Gy cohort. Reduced prescription dose, urethral doses and volumes of high dose regions to the prostate correlated with reduced acute urinary morbidity after Pd-103 brachytherapy. This study suggests that focal treatment approaches with modest dose reductions to subregions of the prostate may reduce acute morbidity and potentially expand the number of patients eligible for brachytherapy. Further investigation is warranted to confirm these effects and the feasibility of focal approaches from a cancer control perspective.

Multi-variable models of large International Prostate Symptom Score worsening at the end of therapy in prostate cancer radiotherapy

Purpose/objectiveProspectively assessing clinical/dosimetry factors affecting the acute worsening of urinary functionality after radiotherapy for prostate cancer. Material/methodsDUE01 population was considered, including patients treated with conventional or moderate hypo-fractionation (2.2–2.7Gy/fr). Relevant clinical factors were collected, urinary symptoms were self-reported through the International Prostate Symptom Score (IPSS) before and at the end of radiotherapy; while absolute weekly dose–surface histograms (DSHw) were chosen as dosimetry descriptors.An IPSS increase of at least 10 and 15 points (ΔIPSS⩾10 and ΔIPSS⩾15) were chosen as endpoints. Patients with baseline IPSS>20 were excluded. Relevant factors were chosen through a bootstrap-based in silico methodology. ResultsComplete information was available for 380 patients: 77/380 (20%) and 28/380 (7%) with ΔIPSS⩾10 and ΔIPSS⩾15, respectively.Neoadjuvant hormone was protective (OR=0.49 and 0.69). DSHw at 8.5Gy/week and 12Gy/week were risk factors, with additional risk for patients who use cardiovascular drugs and anti-hypercholesterolemia drugs.In the hypo-fractionated subgroup (n=209) the role of cardiovascular drugs (OR=2.16) for ΔIPSS⩾10 and anti-hypercholesterolemia drugs (OR=2.80) for ΔIPSS⩾15, together with DSHw (10Gy/week and 12.5Gy/week, respectively), was confirmed. ConclusionCurrent study shows a dose–surface/volume effect for acute large worsening of urinary functionality; several clinical variables largely impact the risk and especially all the factors related with vascular diseases.

Predictors of Acute Urinary Flare Following Stereotactic Body Radiation Therapy (SBRT) in the Definitive Treatment of Localized Prostate Cancer

Clinical studies have demonstrated an association between genitourinary toxicity and dose to critical genitourinary structures in patients treated with brachytherapy and external beam radiation therapy (EBRT) for prostate cancer. The purpose of this study was to identify patient related and dosimetric predictors of acute urinary flare in a prospective cohort of patients undergoing stereotactic body radiation therapy (SBRT) for localized prostate cancer. One hundred three men were treated definitively for localized prostate cancer using robotic SBRT on a prospective institutional protocol. The planning target volume (PTV) consisted of the prostate and proximal seminal vesicles as defined on non-contrast CT and fused T2 MRI with a 3 mm margin at the prostate-bladder interface. Inverse plans were generated with a prescription dose (PD) of 35 to 36.25 Gy in 5 fractions to the PTV using 6 MV photons. Patients who were not already using alpha-receptor antagonists were prophylactically treated with tamsulosin. Patient surveys including the International Prostate Symptom Score (IPSS) were conducted before and one week following the completion of SBRT. Cumulative and differential dose-volume histograms (DVHs) were created for the bladder, bladder wall, bladder neck, and prostatic urethra. Acute urinary flare was defined as an increase in IPSS of 5 points or more with an absolute score of at least 15 points. Twenty-one point four percent of patients experienced acute urinary flare one week following completion of prostate SBRT. Dose-volume cut-off analysis was performed in order to identify statistically significant predictors of acute urinary flare. Univariate regression analysis of patient-related and dosimetric parameters demonstrated that prostatic volume and bladder wall D15.5% were significant predictors of acute urinary flare. Multivariate regression analysis confirmed both prostatic volume and bladder wall D15.5% as significant independent predictors of urinary flare, with a median split prostate volume of 36 cm3 resulting in an 11.8% versus 37.2% incidence of acute flare and a median split dose to the hottest 15.5% of bladder wall of 32.6 Gy resulting in a 9.8% versus 34.6% incidence of acute flare. No dosimetric parameters of the bladder, bladder neck, or prostatic urethra were significantly associated with increased toxicity. Dose-volume histogram analysis of acute urinary toxicity identified that the bladder wall D15.5%, in addition to prostate volume, is a significant predictor of acute urinary flare in patients treated with SBRT for prostate cancer. The consequential effects of acute urinary flare in this prospective cohort of patients treated with prostate SBRT in terms of late urinary toxicity warrants further investigation.

Effect of obesity on International Prostate Symptom Score and prostate volume.

Aim:The aim of this study was to investigate the relationship between obesity and lower urinary tract symptoms and prostate volume in patients who underwent prostate biopsies.Materials and Methods:Between December 2008 and November 2009, transrectal ultrasound-guided prostate biopsy was performed on patients who had elevated prostate-specific antigen levels or abnormal digital rectal examination findings. A total of 211 patients were included in this study. Prostate volumes, International Prostate Symptom Score (IPSS) values, and the patient's height and weight were all recorded during the biopsy. Body mass index (BMI) <18.5 was determined as underweight, 18.5–23.0 normal, 23.0–27.5 overweight, and >27.5 obese.Results:The mean age of the patients was 68.0 ± 6.3 years, and the mean BMI was 28.0 ± 4.9 kg/m2. The mean prostate volume of the normal, overweight, and obese groups was 30, 50, and 70 ml, respectively. The positive and statistically significant correlation between BMI and prostate volume was determined (P < 0.001). According to BMI, the mean IPSS was 8.0, 16.5, and 20.0 in the groups, respectively. Similarly, a statistically positive correlation between BMI and IPSS was demonstrated (P < 0.001).Conclusions:As the result of a rise in BMI, prostate volumes and IPSS increase in patients. Prostate volume and IPSS decrease due to weight loss, and hence that fewer urinary symptoms occur, and the quality-of-life of patients may increase.

Serial Prostate Biopsy and Risk of Lower Urinary Tract Symptoms: Results From a Large, Single-institution Active Surveillance Cohort

To describe the effect of serial prostate biopsy on lower urinary tract symptoms (LUTS) in men who undergo active surveillance (AS) at a large academic institution. This is a retrospective study of men enrolled in AS for≥6 months who underwent≥1 biopsy and completed≥1 International Prostate Symptom Score (IPSS) questionnaire. In additional to total IPSS, we report the mean difference between the first and last questionnaires for patients who completed≥2 questionnaires. Multivariate models, adjusting for disease features, age, race, prostate volume and baseline, or incident benign prostatic hypertrophy (BPH), were used to assess relationships between IPSS and total biopsy exposure. Four hundred eighty-two men were eligible, and 291 completed≥2 IPSS questionnaires. Overall, mean (standard deviation) age was 61.7 (7.8) years, and median prostate volume (interquartile range) was 42 (34-61) mL. At baseline, 11% provided history of BPH. Among men who completed multiple questionnaires, 25% experienced clinically significant worsening (IPSS increase≥4 points). In regression model, total IPSS was not significantly associated with greater biopsy exposure (P= .25). IPSS change from initial and the latest questionnaire was not significantly associated with initial or interval biopsy exposure in an adjusted longitudinal model (P= .64 and .50, respectively), but a trend was observed with greater age decade (+4.07 points, 95% CI-0.30 to 8.4; P= .07). Repeated prostate biopsy does not appear to independently pose additional risk of LUTS in an AS population. In unadjusted analyses, greater biopsy exposure is a surrogate for increasing follow-up time, age, and BPH risk, and thus, risk of LUTS onset and progression.

Long-term follow-up of International Prostate Symptom Score (IPSS) in men following prostate brachytherapy

To investigate variation in the International Prostate Symptom Score (IPSS) in men following prostate brachytherapy. From January 2004 to November 2009, 524 consecutive patients underwent prostate brachytherapy either alone or in combination with external beam radiation therapy for T1c-T3b prostate cancer. The IPSS was assessed preimplant and at 1, 6, 12, 24, 36, and 48 months after treatment. Clinical and treatment-related factors were assessed for correlations with the IPSS increase. The mean preimplant IPSS was 7.4, with the greatest mean score of 16.0 at 1 month. At 6 months, the mean total IPSS had decreased to 11.5, but it was still statistically significantly greater than that at baseline (<0.001). At 12 months, the IPSS was decreased to 8.6, slightly greater than baseline (p = 0.001). The IPSS of 45.4 % (69/152) patients gradually returned to preimplant levels and that of 71.1 % (108/152) patients returned to within 3 points of the baseline at 24 months. At 24, 36, and 48 months after seed implantation, the IPSS was 8.6, 7.7, and 8.2, respectively, and none of these values differed statistically significantly from baseline (p > 0.05). Sixteen patients (3.1 %) showed AUR, and 11 patients required catheterization. On univariate and multivariate analyses, the IPSS increase was best predicted by lower preimplant IPSS. In our series, IPSS after prostate brachytherapy peaked at 1 month and gradually returned to approximately baseline at 24 months. The IPSS increase was best predicted by lower preimplant IPSS.