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Therapeutic efficacy of cisplatin-based treatment of late stage urothelial carcinoma (UC) is limited by chemoresistance. To elucidate underlying mechanisms and to develop new approaches for overcoming resistance, we generated long-term cisplatin treated (LTT) UC cell lines, characterised their cisplatin response, and determined the expression of molecules involved in cisplatin transport and detoxification, DNA repair, and apoptosis. Inhibitors of metallothioneins and Survivin were applied to investigate their ability to sensitise towards cisplatin. Cell growth, proliferation, and clonogenicity were examined after cisplatin treatment by MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, EdU (5-ethynyl-2’-deoxyuridine) incorporation assay, and Giemsa staining, respectively. Cell cycle distribution and apoptosis were quantified by flow cytometry. mRNA and protein expressions were measured by real-time quantitative (qRT)-PCR, western blot, or immunofluorescence staining. LTTs recovered rapidly from cisplatin stress compared to parental cells. In LTTs, to various extents, cisplatin exporters and metallothioneins were induced, cisplatin adduct levels and DNA damage were decreased, whereas expression of DNA repair factors and specific anti-apoptotic factors was elevated. Pharmacological inhibition of Survivin, but not of metallothioneins, sensitised LTTs to cisplatin, in an additive manner. LTTs minimise cisplatin-induced DNA damage and evade apoptosis by increased expression of anti-apoptotic factors. The observed diversity among the four LTTs highlights the complexity of cisplatin resistance mechanisms even within one tumour entity, explaining heterogeneity in patient responses to chemotherapy. [ABSTRACT FROM AUTHOR]

Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To examine the relationship between body mass index (BMI) and biochemical recurrence (BCR), cancer-specific (CSS) and overall survival (OS) in men treated with permanent prostate brachytherapy (PPB), as there is limited information on the affect of obesity on treatment outcomes for prostate cancer. PATIENTS AND METHODS In all, 1530 patients with clinically localized prostate cancer who underwent PPB were studied. Clinical and pathological data were retrospectively obtained from medical records. The BMI was classified as normal (<25 kg/m2), overweight (25–30 kg/m2) and obese (≥30 kg/m2). BCR was defined as a rise in PSA levels of ≥2 ng/mL after the nadir had been reached. The cause of death was determined for each deceased patient. Patients with metastatic prostate cancer who died of any cause were classified as prostate cancer deaths. RESULTS In all, 617 (40%) patients were classified as having a normal weight, 754 (49%) overweight and 159 (10%) were obese. The Kaplan–Meier 8-year risk of BCR (95% confidence interval) was 33.3% (27.2–39.4), 29.2% (23.5–34.9) and 29.3% (12.4–46.2) for patients with a BMI of <25 kg/m2, 25–30 kg/m2 and ≥30 kg/m2, respectively. The 8-year CSS was 88.2% (83.1–93.3), 88.6% (83.7–93.5) and 90.6% (79.9–101.4) and the 8-year OS was 70.1% (63.6–76.6), 72.9% (66.6–79.2) and 81.8% (69.3–94.3) for these three groups, respectively. Multivariate proportional hazard regression analyses of BMI and established prognostic factors for BCR confirmed the absence of any prognostic value of BMI on BCR, CSS and OS. CONCLUSIONS BMI did not appear to have any prognostic value for BCR, CCS or OS in patients with clinically localized prostate cancer treated with PPB. [ABSTRACT FROM AUTHOR]

Objective: The increasing incidence of both obesity and prostate cancer (PCa) detection will confront the urologist more often with obese men having PCa. It is unknown whether obesity affects the surgical and oncological outcomes following open radical retropubic prostatectomy (RRP). Knowledge concerning this issue is relevant when counselling obese patients with PCa for RRP. Patients and Methods: A single institution cohort study was performed including 252 men who underwent a RRP between 1992 and 2003. The surgical complications (perioperative complications, post-RRP urinary incontinence, urethral strictures) were compared between obese (BMI >30) and nonobese (BMI ≤30) men. Results: Compared to nonobese (n = 221), obese men (n = 31) developed more frequently wound infections (16.1 vs. 4.5%; p < 0.05), urinary incontinence (25.8 vs. 8.7%; p < 0.05) as well as vesico-urethral strictures (46.2 vs. 12.3%; p < 0.05). The pathology results and the 5-year cumulative risk of PSA recurrence were comparable among both groups. Conclusions: Compared to nonobese, obese men suffer more frequently from post-RRP urinary incontinence and vesicourethral strictures following open RRP. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The author comments on a study on the outcome of treating prostate cancer in obese patients through radical prostatectomy, published within this issue. The author mentions that, obese patients treated with radical prostatectomy has increased risks of biochemical recurrence and obesity makes many urological procedures more challenging and complex. The author further mentions that, advanced prostate cancer is more strongly related to abdominal adiposity than with the body mass index.

Objective: The purpose of this review was to summarize the current literature on the assessment and treatment of radiation urethritis and cystitis (RUC) for the development of an evidenced-based management algorithm., Material and Methods: The PubMed/MEDLINE database was searched by a multidisciplinary group of experts in January 2021., Results: In total, 48 publications were identified. Three different types of RUC can be observed in clinical practice: inflammation-predominant, bleeding-predominant, and the combination of inflammation- and bleeding-RUC. There is no consensus on the optimal treatment of RUC. Inflammation-predominant RUC should be treated symptomatically based on the existence of bothersome storage or voiding lower urinary tract symptom as well as on pain. When bleeding-predominant RUC has occurred, hydration and hyperbaric oxygen therapy (HOT) should be used first and, if HOT is not available, oral drugs instead (sodium pentosane polysulfate, aminocaproic acid, immunokine WF 10, conjugated estrogene, or pentoxifylline + vitamin E). If local bleeding persists, focal therapy of bleeding vessels with a laser or electrocoagulation is indicated. In case of generalized bleeding, intravesical installation should be initiated (formalin, aluminium salts, and hyaluronic acid/chondroitin). Vessel embolization is a less invasive treatment with potentially less complications and good clinical outcomes. Open- or robot-assisted surgery is indicated in patients with permanent, life-threatening bleeding, or fistulae., Conclusions: Treatment of RUC, if not self-limiting, should be done according to the type of RUC and in a stepwise approach. Conservative/medical treatment (oral and topic agents) should primarily be used before invasive (transurethral) treatments., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Purpose of Review: After radical cystectomy (RC) patients are at risk for both benign and malignant problems regarding the upper urinary tract (UUT). This review summarizes the recent literature and provides tips on how to manage problems of the UUT after RC., Recent Findings: Disease recurrence, kidney stones and ureteroenteric strictures (UES) are common after RC. Endourological techniques can be used to treat low-grade disease recurrence, either with a retrograde or antegrade approach. Treatment success depends on getting access to the UUT and on tumor characteristics; selecting the right approach is key. Kidney stones can be treated endourologically with good results. With use of minimal invasive techniques such as robot cystectomy, a higher incidence of UES is observed. The use of indocyanine green could help to prevent this complication. In case of a stricture, primary reconstruction should be the treatment strategy of choice., Summary: After RC, recurrence of the UUT remains a complicated problem. Choice of treatment method should be tailored to the patient and tumor characteristics. Kidney stones after cystectomy can be successfully managed endourological. Robot assisted RC introduced a higher rate of UES, which should be managed by primary revision., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Prostate cancer radiotherapy (RT) in patients with (active) inflammatory bowel disease (IBD) remains controversial. We hypothesized that RT in combination with a biodegradable prostate-rectum spacer balloon implantation, might be a safe treatment approach with acceptable toxicities for these high risk for rectal toxicity patients., Materials and Methods: We report on a small prospective mono-centric series of 8 patients with all-risk prostate cancer with the comorbidity of an IBD. Four patients had Crohn's disease and 4 patients had ulcerative colitis. One out of four had an active status of IBD. All patients were intended to be treated with curative high-dose RT: 5 patients were treated with external beam RT (70 Gray (Gy) in 28 fractions), and 3 patients were treated with 125 I-implant (145 Gy). Toxicities were scored according to the CTCAE v4.03: acute side effects occur up to 3 months after RT, and late side effects start after 3 months., Results: Median follow-up was 13 months (range: 3-42 months). Only one acute grade 2 gastro-intestinal (GI) toxicity was observed: an increased diarrhea (4-6 above baseline) during RT, which resolved completely 6 weeks after treatment. No late grade 3 or more GI toxicity was reported, and no acute and late grade ≥2 genitourinary toxicity events were observed., Conclusion: Prostate cancer patients with IBD are a challenge to treat with RT. Our results suggest that RT in combination with a balloon implant in selective patients with (active) IBD may be promising, however additional validation is needed., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Author(s).)

Background: Prostate biopsy, an invasive examination, is the gold standard for diagnosing prostate cancer (PCa). There is a need for a novel noninvasive diagnostic tool that achieves a significantly high pretest probability for PCa, reducing unnecessary biopsy numbers. Recent studies have shown that volatile organic compounds (VOCs) in exhaled breath can be used to detect different types of cancers via training of an artificial neural network (ANN)., Objective: To determine whether exhaled-breath analysis using a handheld electronic nose device can be used to discriminate between VOC patterns between PCa patients and healthy individuals., Design, Setting, and Participants: This prospective pilot study was conducted in the outpatient urology clinic of the Maastricht University Medical Center, the Netherlands. Patients with histologically proven PCa were already included before initial biopsy or during follow-up, with no prior treatment for their PCa. Urological patients with negative biopsies in the past year or patients with prostate enlargement (PE) with low or stable serum prostate-specific antigen were used as controls. Exhaled breath was probed from 85 patients: 32 with PCa and 53 controls (30 having negative biopsies and 23 PE)., Outcome Measurements and Statistical Analysis: Patient characteristics were statistically analyzed using independent sample t test and Pearson's chi-square test. Data analysis was performed by Aethena software after data compression using the TUCKER3 algorithm. ANN models were trained and evaluated using the leave-10%-out cross-validation method., Results and Limitations: Our trained ANN showed an accuracy of 0.75, with an area under the curve of 0.79 with sensitivity and specificity of 0.84 (95% confidence interval [CI] 0.66-0.94) and 0.70 (95% CI 0.55-0.81) respectively, comparing PCa with control individuals. The negative predictive value was found to be 0.88. The main limitation is the relatively small sample size., Conclusions: Our findings imply that the Aeonose allows us to discriminate between patients with untreated, histologically proven primary PCa and control patients based on exhaled-breath analysis., Patient Summary: We explored the possibility of exhaled-breath analysis using an electronic nose, to be used as a noninvasive tool in clinical practice, as a pretest for diagnosing prostate cancer. We found that the electronic nose was able to discriminate between prostate cancer patients and control individuals., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

This clinical lesson, based on two case histories, illustrates a complication seen after manipulation of the rectal wall in patients who have undergone radiotherapy for localised prostate cancer. Rectal bleeding, which is feared by patients, can be the first sign of radiation proctitis. Manipulation of the rectal wall, for example by taking biopsies or Argon plasma coagulation, should be done with caution and only if absolutely necessary, because it can lead to fistula formation.

Purpose: To investigate the association between prostate specific antigen (PSA) bounce and disease outcome after prostate brachytherapy., Methods and Materials: We analyzed 975 patients treated with (125)I implantation monotherapy between 1992 and 2006. All patients had tumor Stage ≤ 2c, Gleason score ≤ 7 prostate cancer, a minimum follow-up of 2 years with at least four PSA measurements, and no biochemical failure in the first 2 years. Median follow-up was 6 years. Bounce was defined as a PSA elevation of +0.2 ng/mL with subsequent decrease to previous nadir. We used the Phoenix +2 ng/mL definition for biochemical failure. Additional endpoints were disease-specific and overall survival. Multivariate Cox regression analysis was performed to adjust for potential confounding factors., Results: Bounce occurred in 32% of patients, with a median time to bounce of 1.6 years. More than 90% of bounces took place in the first 3 years after treatment and had disappeared within 2 years of onset. Ten-year freedom from biochemical failure, disease-specific survival, and overall survival rates were, respectively, 90%, 99%, and 88% for the bounce group and 70%, 93%, and 82% for the no-bounce group. Only 1 patient (0.3%) died of prostate cancer in the bounce group, compared with 40 patients (6.1%) in the no-bounce group. Adjusted for confounding, a 70% biochemical failure risk reduction was observed for patients experiencing a bounce (hazard ratio 0.31; 95% confidence interval 0.20-0.48)., Conclusions: A PSA bounce after prostate brachytherapy is strongly related to better outcome in terms of biochemical failure, disease-specific survival, and overall survival., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Study Type: Prognostic (case series)., Level of Evidence: 4. What's known on the subject? and What does the study add? Nowadays more and more publications have been published about the topic prostate cancer aggressiveness and obesity with mixed results. However, most of the publications used the BMI as a marker for obesity, while the most metabolic active fat is the visceral fat. To learn more about these relations we measured and used the visceral fat in our paper., Objective: To examine if the periprostatic fat measured on computed tomography (CT) correlates with advanced disease we examined patients who received radiotherapy for localized prostate cancer. Several USA reports found a positive association between obesity and prostate cancer aggressiveness. However, in recent European studies these conclusions were not confirmed. Studies concerning this issue have basically relied on body mass index (BMI), as a marker of general obesity. Visceral fat, however, is the most metabolically active and best measured on CT., Patients and Methods: In 932 patients, who were treated with external radiotherapy (N=311) or brachytherapy (N=621) for their T1-3N0M0 prostate cancer, different fat measurements (periprostatic fat, subcutaneous fat thickness) were performed on a CT. Associations between the different fat measurements and risk of having high-risk (according to Ash et al., PSA>20 or Gleason score≥8 or T3) disease was measured., Results: The median age (IQR) was 67.0 years (62.0-71.0) and median BMI (IQR) was 25.8 (24.2-28.3). Logistic regression analyses, adjusted for age, revealed a significant association between periprostatic fat density (PFD) and risk of having a high risk disease. (Odds ratio [95% CI] 1.06 [1.04-1.08], P<0.001), Conclusion: Patients with a higher PFD had more often aggressive prostate cancer., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Objective: • To compare survival after prostate brachytherapy in patients aged ≤60 years with patients aged >60 years., Patients and Methods: • We analysed 419 locally confined prostate cancer patients, treated between 1989 and 2001 with I-125 implantation monotherapy. • Endpoints were biochemical failure (BF) according to the +2 ng/mL definition, disease-specific and overall survival. • Patients were subdivided into age ≤60 years and age >60 years. • Cox proportional-hazards regression analyses were performed to study the independent effect of age on BF and disease-specific survival., Results: • The younger cohort consisted of 87 patients (21%), with smaller prostate volumes and a lower average prostate cancer risk class than the older cohort, consisting of 332 patients (79%). Mean follow-up was 9.1 years (±sd 2.8) for the younger cohort and 8.3 years (±sd 2.9) for the older cohort. • The 10-year (95% CI) freedom from BF, disease-specific survival and overall survival rates were 63% (51-75), 87% (78-96) and 81% (69-89), respectively, for the younger cohort and 46% (39-54), 83% (78-89) and 60% (54-66), respectively, for the older patient cohort. • Although a trend for better freedom from BF and disease-specific survival was observed in younger patients, the difference proved not clinically significant., Conclusion: • Prostate cancer risk group and the year of treatment relate to outcome, but not age. With respect to prostate cancer curability, there seems no objection to offer brachytherapy to patients aged 60 years and younger., (© 2010 THE AUTHORS. BJU INTERNATIONAL © 2010 BJU INTERNATIONAL.)

Purpose: To assess the influence of dose in different prostate regions, and the influence of anatomic variation on the risk of acute urinary retention (AUR) after I-125 prostate brachytherapy., Methods and Materials: In this case-control study, dosimetry and anatomy were compared between 50 patients with AUR (cases) and 50 patients without AUR (controls). Cases and controls were randomly selected from our database. The following structures were delineated on magnetic resonance imaging: prostate, urethra, peripheral zone, transitional zone, apex, base, midprostate, lower sphincter, and bladder neck. The dosimetric parameters analyzed were D(10), D(50), D(90), V(100), V(150), and V(200). The anatomic parameters analyzed were prostate protrusion into the bladder, bladder overlap, urethra angle, and urethra-bladder angle. The delineator was blinded to the patient's AUR status. Logistic regression analysis was used to investigate the association of these factors with AUR., Results: The dose delivered to different regions of the prostate was not significantly associated with the risk of AUR. Only dose to the bladder neck was significantly associated with AUR (odds ratio 1.13 per 10 Gy; 95% CI 1.02;1.26; p = 0.023). Mean bladder neck D(90) was 65 Gy in AUR cases vs. 56 Gy in controls (p = 0.016), and mean bladder neck D(10) was 128 Gy vs. 107 Gy, respectively (p = 0.018). Furthermore, on univariate analysis, a larger extent of both bladder overlap and of prostate protrusion were associated with a higher risk of AUR (odds ratio 1.16; 95% CI 1.04-1.28; p = 0.005, and odds ratio 1.83; 95% CI 1.37-2.45; p < 0.001, respectively). The mean extent of prostate protrusion was 3.5 mm in AUR cases vs. 1.0 mm in controls (p < 0.001). Odds ratios did not change substantially after adjustment for potential confounders. On multivariate analysis, the extent of prostate protrusion seemed to be a stronger risk factor for AUR than bladder overlap., Conclusion: The risk of AUR is not associated with dose delivered to different regions of the prostate. However, a higher dose to the bladder neck and a larger extent of prostate protrusion into the bladder are risk factors for the development of AUR after I-125 prostate brachytherapy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: To evaluate the impact of acute urinary retention (AUR) in patients treated with (125)I prostate brachytherapy on short- and long-term health-related quality of life (HRQOL); and to assess whether pretreatment HRQOL has additional value in the prediction of AUR., Methods and Materials: For 127 patients treated with (125)I brachytherapy for localized prostate cancer between December 2000 and June 2003, toxicity and HRQOL data were prospectively collected. Patients received a HRQOL questionnaire at five time points: before and 1 month, 6 months, 1 year, and 6 years after treatment. The questionnaire included the RAND-36 generic health survey, the cancer-specific European Organization for Research and Treatment of Cancer core questionnaire (EORTC QLQ-C30), the tumor-specific EORTC prostate cancer module (EORTC QLQ-PR25), and the American Urological Association (AUA) symptom index., Results: Of 127 patients, 13 (10.2%) developed AUR. Patients with AUR had a significantly worse urinary QOL at all time points compared with patients without AUR. The mean difference over time (6 years) between both groups for the EORTC QLQ-PR25 urinary symptom score was 13.0 points (p < 0.001) and for the AUA urinary symptom score was 15.7 points (p = 0.001). Global QOL scores (EORTC QLQ-C30) over time for patients who developed AUR were significantly worse compared with patients without AUR (mean difference 6.7 points; p = 0.043). In multivariate logistic regression analysis, pretreatment International Prostate Symptom Score (p = 0.004) and neoadjuvant hormonal treatment (p = 0.034) were predictors of AUR. Quality of life did not have added predictive value., Conclusion: Acute urinary retention after prostate brachytherapy has a significant negative impact on patient's HRQOL up to 6 years after treatment, in terms of both global QOL measures and urinary symptom scores. Furthermore, our results suggest limited value of pretreatment HRQOL measures for the prediction of AUR., (Copyright 2010 Elsevier Inc. All rights reserved.)

Purpose: To assess clinical outcome in terms of biochemical No evidence of disease (bNED) for patients with stranded seed implants versus loose seed implants in prostate brachytherapy., Methods: From December 2000 until October 2006, we treated 896 T< or =2C Nx/0 Mx/0, prostate cancer patients with either stranded seed (n=538) or loose seed (n=358) I-125 implants. A total of 211 patients received a 6 months course of anti-androgen therapy, before treatment, for prostate volume reduction to <50 cc. Patients with very small and large gland volumes or a history of transurethral prostate resection, were preferably treated with stranded seeds, otherwise selection was arbitrary., Results: The 5-year bNED rates (95% Confidence Interval) for stranded seed patients and loose seed patients were respectively 86% (82-90) and 90% (85-95), the total 5-year bNED rate was 87% (85-90). When adjusted for possible confounding factors in a Cox-regression analysis, type of seed was significantly associated with biochemical failure with a 43% risk reduction (hazard ratio: 0.57; 95% CI: 0.34-0.97) for loose seeds versus stranded seeds., Conclusions: These results suggest that seed-type affects clinical outcome in prostate brachytherapy, with better bNED for patients with loose seed implants., (Copyright 2010. Published by Elsevier Ireland Ltd.)

Purpose: To assess long-term biochemical and survival outcome after permanent prostate brachytherapy (BT)., Methods and Materials: Data on 921 patients, treated with permanent interstitial BT monotherapy between 1989 and 2004 for or=50cc received 6 months of antiandrogen therapy before treatment. Patients were classified into risk groups with 232 defined as low-, 369 intermediate-, and 320 high-risk disease. The median follow-up was 69 months (range, 4-186 months); mean age was 67 years., Results: Average 5- and 10-year biochemical no evidence of disease (bNED) rates were 79% and 57%. Average 10-year bNED rates by risk group were 88% for low-risk, 61% for intermediate-risk, and 30% for high-risk disease. The average 10-year overall and disease-specific survival rates were 59% and 82%. Ten-year overall and disease-specific survival rates by risk group were, respectively, 68% and 96% for low-risk, and 64% 87% for intermediate-risk, and 49% and 69% for high-risk disease. In multivariate Cox regression analysis, both risk group and treatment era were independent predictors of bNED and survival., Conclusions: These data on long-term survival continue to support the use of I-125 monotherapy for prostate cancer in low-risk patients and, in particular, demonstrate its efficacy in intermediate-risk patients.

Objective: To investigate whether body mass index (BMI) is a prognostic factor for biochemical recurrence (BCR) in Dutch men after radical prostatectomy (RP), as although epidemiological studies of obesity in relation to prostate cancer have provided conflicting results, recent studies from the USA suggest that a higher BMI is a risk factor for progression of prostate cancer., Patients and Methods: Of the 1417 patients with prostate cancer who had RP at two University hospitals, 1302 were included in the present study. BMI (kg/m(2)) classes were defined as normal (<25), overweight (25-30) and obese (> or =30). The median follow-up was 59 months and clinical data were obtained retrospectively from charts. BCR was defined as two consecutive prostate-specific antigen (PSA) levels of >0.1 ng/mL., Results: In all, 600 patients were classified as having normal weight (43.9%), 665 as overweight (48.6%) and 103 as obese (7.5%). Overall, 297 patients developed BCR after RP; the 10-year risk (95% confidence interval) of BCR was 31.9 (26.6-37.2)%, 30.5 (25.8-35.2)% and 23.9 (14.9-32.9)% for patients in the three categories, respectively (P = 0.836). Multivariable proportional hazard regression analyses of BMI and established prognostic factors for BCR did not change these results., Conclusion: BMI appeared to have no prognostic value for BCR in Dutch patients with clinically localized prostate cancer and treated with RP.