Contemporary validation of cT1a vs. cT1b substaging of incidental prostate cancer.

OBJECTIVE: The cT1a vs. cT1b substratification was introduced in 1992 but never formally tested since. We tested the discriminative ability of cT1a vs. cT1b substaging on cancer-specific survival (CSS) in contemporary incidental prostate cancer (PCa) patients. DESIGN, SETTING AND PARTICIPANTS: Incidental (cT1a/cT1b) PCa patients were identified within the Surveillance, Epidemiology, and End Results (SEER) database (2004-2015). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier estimates, as well as uni- and multivariable Cox regression models predicted CSS at five years. Subgroup analyses addressed CSS at five years according to active vs. no local treatment (NLT) as well as Gleason score sum (GS; 6 vs. 7 vs. ≥ 8). RESULTS AND LIMITATION: We identified a total of 5,155 incidental prostate cancer patients of which 3,035 (59%) were stage cT1a vs. 2,120 (41%) were stage cT1b. In all incidental PCa patients, CSS at five years was 95% (95% CI 0.94-0.96). In cT1a patients, CSS at five years was 98 vs. 90% in cT1b patients (p < 0.001). In multivariable Cox regression analyses, cT1b independently predicted 2.8-fold higher CSM than cT1a (HR 2.5, 95% CI 1.8-3.6, p < 0.001) for incidental PCa patients who underwent NLT. In subgroup analyses, cT1b represented an independent predictor of higher CSM in GS ≥ 8 (HR 3.0, 95% CI 1.4-6.2, p = 0.003), and GS 7 (HR 3.9, 95% CI 1.6-9.7 p = 0.002) patients who underwent NLT. For actively treated patients, cT1b was not independently associated with worse CSM. CONCLUSION: The historical subclassification of cT1a vs. cT1b in incidental PCa patients displayed a strong ability to discriminate CSS in contemporary GS 7 and GS ≥ 8 patients who underwent NLT. However, no statistically significant difference was recorded in actively treated patients. In consequence, the importance of the current substage stratification predominantly applies to GS ≥ 8 patients who undergo a non-active treatment approach.

Charlson-Deyo Comorbidity Index as a Novel Predictor for Recurrence in Non-Muscle-Invasive Bladder Cancer.

PURPOSE: To test the association between the Charlson-Deyo Comorbidity Index (CCI) and the recurrence of non-muscle-invasive bladder cancer (NMIBC). METHODS: NMIBC (Ta, T1, TIS) patients who underwent transurethral resection of bladder tumor (TURB) between 2010 and 2018 were identified within a retrospective data repository of a large university hospital. Kaplan-Meier estimates and uni- and multivariable Cox regression models tested for differences in risk of recurrence according to low vs. high comorbidity burden (CCI ≤ 4 vs. >4) and continuously coded CCI. RESULTS: A total of 1072 NMIBC patients were identified. The median follow-up time of the study population was 55 months (IQR 29.6-79.0). Of all 1072 NMIBC patients, 423 (39%) harbored a low comorbidity burden vs. 649 (61%) with a high comorbidity burden. Overall, the rate of recurrence was 10% at the 12-month follow-up vs. 22% at the 72-month follow-up. In low vs. high comorbidity burden groups, rates of recurrence were 6 vs. 12% at 12 months and 18 vs. 25% at 72 months of follow-up (p = 0.02). After multivariable adjustment, a high comorbidity burden (CCI > 4) independently predicted a higher risk of recurrence (HR 1.42, 95% confidence interval (CI) 1.06-1.92, p = 0.018). After multivariable adjustment, the hazard of recurrence increased by 5% per each one-unit increase on the CCI scale (HR 1.05, 95% CI 1.00-1.10, p = 0.04). CONCLUSIONS: Comorbidities in NMIBC patients are common. Our data suggest that patients with higher CCI have an increased risk of BC recurrence. As a consequence, patients with a high comorbidity burden should be particularly encouraged to adhere to NMIBC guidelines and conform to follow-up protocols.

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery.

PURPOSE: Upper tract urothelial carcinoma (UTUC) represents an often aggressive malignancy associated with poor prognosis. Therefore, finding reliable prognostic biomarkers in patients undergoing curative surgery for improved risk stratification is crucial. We evaluated the prognostic value of the Fibrinogen/C-reactive protein (FC)-score in a cohort of surgically treated UTUC patients. METHODS: 170 patients with radiologically and histologically verified UTUC who underwent radical curative surgery between 1990 and 2020, were included. The FC-score was calculated for each patient, with patients receiving 1 point each if Fibrinogen and/or CRP levels were elevated above the 25th or 75th percentile, respectively. Patients were divided into three subgroups according to their FC-score of 0, 1 or 2 point(s). Kaplan-Meier analysis, uni- and multivariable Cox proportional hazard models were implemented. We determined cancer-specific survival (CSS) as primary endpoint, whereas overall survival (OS) and recurrence-free survival (RFS) were considered secondary endpoints. RESULTS: High FC-score (2 points) was significantly associated with adverse histological features such as vascular invasion (OR = 4.08, 95%CI 1.18-14.15, p = .0027) and tumour necrosis (OR = 6.67, 95%CI 1.35-32.96, p = 0.020). Both, uni- and multivariable Cox proportional hazard models showed the FC-score as a significant predictor for CSS (univariable analysis: FC-score = 1: HR = 1.90, 95%CI 0.92-3.93, p = 0.085 | FC-score = 2: HR = 2.86, 95%CI 1.22-6.72, p = 0.016). Furthermore, in univariable analysis, patients with higher FC-score had significantly shorter OS (FC-score = 1: HR = 1.32, 95%CI 0.70-2.49, p = 0.387 | FC-score = 2: HR = 2.19, 95%CI 1.02-4.67, p = 0.043). However, this did not prevail in multivariable analysis. CONCLUSION: The FC-score represents a novel potential biomarker in patients with UTUC undergoing radical curative surgery.

Improved overall survival of metastatic renal cell carcinoma patients in the era of modern tyrosine kinase inhibitors and immune checkpoint inhibitors: results from a real-life, population-based Austrian study comprising three decades of follow-up.

Background: The treatment landscape of metastatic renal cell carcinoma (mRCC) has substantially advanced over the last three decades, whereby data from controlled clinical trials indicate significant improvements regarding patients' overall survival (OS) in highly selected patient cohorts. The aim of this study is to evaluate the impact of potentially game changing drugs on patients' outcomes by comparing three different historical mRCC treatment eras. Methods: In all, 914 mRCC patients who were diagnosed between July 1985 and September 2020 were included into this observational study and assigned to three different treatment eras ['cytokine', 'first-generation tyrosine kinase inhibitors (TKIs)', and 'modern TKIs/immunotherapy'] based on the EMA approval dates of sunitinib (July 2006) and nivolumab (June 2015) in mRCC treatment. OS was considered the primary study endpoint. Kaplan-Meier analyses, log-rank tests, and uni- and multivariable Cox regression models were performed. Results: OS was significantly longer in patients of the modern TKIs/immunotherapy era (median OS not reached) as compared to the cytokine (2.4 years) and first-generation TKIs era (1.7 years, all p < 0.001). Moreover, patients of the modern TKIs/immunotherapy era demonstrated a significantly better prognosis [hazard ratio (HR): 0.41, 95% confidence interval (CI): 0.32-0.55, p < 0.001] compared to those of the cytokine era, while no statistically significant difference was observed between the cytokine and the first-generation TKIs era cohort (HR: 1.12, 95% CI: 0.89-1.41, p = 0.341). Subgroup analyses stratified by the International Metastatic RCC Database Consortium (IMDC) risk groups showed a significantly longer OS in the modern TKIs/immunotherapy era as compared to first-generation TKIs and cytokines across all IMDC risk groups. Conclusion: Significant advances in the systemic medical treatment of mRCC during the recent decade and the introduction of immunotherapy exerted a major impact on patient outcomes in terms of OS in a real-life population.

Combining targeted and systematic prostate biopsy improves prostate cancer detection and correlation with the whole mount histopathology in biopsy naïve and previous negative biopsy patients.

Objective: Guidelines for previous negative biopsy (PNB) cohorts with a suspicion of prostate cancer (PCa) after positive multiparametric (mp) magnetic-resonance-imaging (MRI) often favour the fusion-guided targeted prostate-biopsy (TB) only approach for Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesions. However, recommendations lack direct biopsy performance comparison within biopsy naïve (BN) vs. PNB patients and its prognostication of the whole mount pathology report (WMPR), respectively. We suppose, that the combination of TB and concomitant TRUS-systematic biopsy (SB) improves the PCa detection rate of PI-RADS 2, 3, 4 or 5 lesions and the International Society of Urological Pathology (ISUP)-grade predictability of the WMPR in BN- and PNB patients. Methods: Patients with suspicious mpMRI, elevated prostate-specific-antigen and/or abnormal digital rectal examination were included. All PI-RADS reports were intramurally reviewed for biopsy planning. We compared the PI-RADS score substratified TB, SB or combined approach (TB/SB) associated BN- and PNB-PCa detection rate. Furthermore, we assessed the ISUP-grade variability between biopsy cores and the WMPR. Results: According to BN (n = 499) vs. PNB (n = 314) patients, clinically significant (cs) PCa was detected more frequently by the TB/SB approach (62 vs. 43%) than with the TB (54 vs. 34%) or SB (57 vs. 34%) (all p < 0.0001) alone. Furthermore, we observed that the TB/SB strategy detects a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports, both in BN and PNB men. In contrast, applied biopsy techniques were equally effective to detect csPCa within PI-RADS 2 lesions. In case of csPCa diagnosis the TB approach was more often false-negative in PNB patients (BN 11% vs. PNB 19%; p = 0.02). The TB/SB technique showed in general significantly less upgrading, whereas a higher agreement was only observed for the total and BN patient cohort. Conclusion: Despite csPCa is more frequently found in BN patients, the TB/SB method always detected a significantly higher number of csPCa within PI-RADS 3, 4 or 5 reports of our BN and PNB group. The TB/SB strategy predicts the ISUP-grade best in the total and BN cohort and in general shows the lowest upgrading rates, emphasizing its value not only in BN but also PNB patients.

Prognostic relevance of ABO blood group system in non-metastatic renal cell carcinoma: An analysis of two independent European cohorts with long-term follow-up.

BACKGROUND: The ABO blood group system has been previously discussed as a risk factor to develop, as well as a prognostic factor in non-metastatic renal cell carcinoma (RCC). Controversial findings have been reported in different populations of RCC patients with rather short follow-up periods. In this study, we aimed to clarify the distribution and prognostic role of ABO blood groups upon 15 years of median follow-up in non-metastatic RCC patients. MATERIALS AND METHODS: We evaluated the distribution and prognostic significance of ABO blood group system in two independent cohorts (n = 405 and n = 1473) of non-metastatic RCC patients, who underwent curative (partial or total) nephrectomy between 1998 and 2012 at two tertiary academic centers. Cancer-specific survival, metastasis-free survival, as well as overall survival (OS) were assessed using the Kaplan-Meier method, univariable- and multivariable Cox regression models were applied, respectively. RESULTS: In the two cohorts, blood groups were not associated with any clinical endpoints (for cohort 2: Cancer-specific survival (HR = 1.233; 95%CI 0.998-1.523, P = 0.052), metastasis-free survival (HR = 1.161; 95%CI 0.952-1.416, P = 0.142) and OS (HR = 1.037; 95%CI 0.890-1.208, P = 0.641), respectively). Compared to 250.298 healthy blood-donors of the Styrian state, the distribution of blood groups was (624 (42.4%) versus 106.861 (42.7%) in group A, 191 (13%) vs. 34.164 (13.7%) in group B, 575 (39%) versus 93.579 (37.4%) in group O and 83 (5.6%) vs. 15.694 (6.3%), P = 0.467). CONCLUSION: In this large study with the longest period of follow-up reported to date, the ABO blood group system could not be validated as a prognostic factor in predicting important clinical endpoints in non-metastatic RCC patients.

Utility of pT3 substaging in lymph node-negative urothelial carcinoma of the bladder: do pathologic parameters add to prognostic sub-stratification?

PURPOSE: The value of bladder cancer (BC) substaging into macroscopic (pT3b) and microscopic (pT3a) perivesical fat extension in lymph node (Ln)-negative patients is controversially discussed and limited evidence for prognostic relevance of additional histopathological factors in pT3 BC exists. We evaluated the prognostic value of pT3 substaging and established pathological and clinical parameters with focus on tumor invasive front (TIF) and tumor size. METHODS: Specimens of 52 patients treated with radical cystectomy (RC) for pT3 a/b muscle-invasive BC were reviewed and re-evaluated by a pathologist specialized in uropathology. Clinical variables and standard histopathologic characteristics were assessed including TIF and tumor size. Their value as prognosticators for overall survival (OS) and recurrence-free survival (RFS) was evaluated. RESULTS: Mean age of patients was 67.55 years. Tumors were staged pT3a in 28 patients (53.8%) and pT3b in 24 (46.8%). Median OS was 34.51 months. Median tumor size was 3.2 cm, median TIF was 11.0 mm. Differences in OS between pT3a and pT3b were not significant (p = 0.45). Carcinoma in situ (CIS) and lymphovascular invasion (LVI) were significantly associated with pT3b tumors. Univariate analysis could not identify pathological prognosticators like TIF or tumor size for OS and RFS (p for all > 0.05). CONCLUSION: No significant differences in OS or RFS were observed comparing Ln-negative pT3 BC following radical cystectomy. Additional pathologic variables like TIF could not be identified as prognosticator. Relevance of pT3 BC substaging needs reevaluation in larger prospective cohorts.

A Modified Neobladder Technique: The "I-Pouch" - Illustration of Surgical Approach and Tricks.

OBJECTIVE: Various techniques for orthotopic neobladder (ONB) are currently used and have shown satisfactory oncological and functional outcomes.3 Among the relevant oncological and functional aspects for long-term follow up is the easy accessibility of the upper urinary tract in urinary diversion for endoscopic monitoring. In addition, variety exists in the amount of ileum needed to create a urinary reservoir. Depending on the ONB technique, up to 60 cm of ileum are required, and bowel dysfunction may be a consequence especially when the ileocecal valve is used for the urinary diversion. We previously reported the technique, functional and oncologic results of the I-pouch, a modified ONB made of 40 cm of ileum, combining an antirefluxive ureter implantation technique with easy access to the uretero-intestinal anastomosis.1,2 The present video is intended to illustrate key surgical steps and pitfalls during the procedure. METHODS: The technique, surgical tips, and functional results in a as compared to a institutional control group receiving conventional Studer -Pouch-procedure are outlined. RESULTS: In a follow up series of 33 I-pouch and 23 S-pouch patients, there were no differences according to ONB type for 30-day major- (P = .33) and minor (P = 0.96) complication rates although 90-day major (P = 0.08) and minor (P = 0.08) complication rates tended to be associated with less complications in I-pouch patients. CONCLUSION: The I-pouch can be used for neobladder substitution providing easy access to the upper urinary tract, reduced demand of ileum length along with a complication profile not distinct from Studer neobladder formation.

Prognostic value of B7-H1, B7-H3 and the stage, size, grade and necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma.

INTRODUCTION: We compared the potential prognostic impact of B7-H1 and B7-H3 glycoprotein expressions with the Mayo Clinic Stage, Size, Grade, and Necrosis (SSIGN) score in metastatic clear cell renal cell carcinoma (mccRCC) during a long term follow-up. MATERIAL AND METHODS: We investigated 44 mccRCC patients, who underwent radical nephrectomy between 1995 and 2006 at a single tertiary academic center and received interferon therapy (IFNT) for at least three months. The SSIGN score was applied as a validated prediction outcome model. Representative tumor sections were immunostained with anti-B7-H3 and anti-B7-H1 antibodies. Hereafter, positive antigen-antibody reactions were measured using the Positive-Pixel-Count Algorithm of the Aperio-Technology Image Scope software. RESULTS: In total, 48% of patients were treated with cytoreductive nephrectomy and postoperative IFNT due to synchronous mccRCC, whereas 52% received IFNT after developing metachronous mccRCC. The SSIGN score was independently associated with a higher mortality risk. Patients with a SSIGN score ≤9 showed an extended 'nephrectomy to start of INFT'-interval (p = 0.02), less synchronous clinical metastases (p = 0.0002), as well as an increased median overall - (OS) or cancer-specific survival (CSS) (p = 0.01), respectively. Furthermore, B7-H3 expression levels of ≤16% were associated with an improved OS or CSS and correlated with a more frequent pathologic grade 1-2, as well as a longer 'nephrectomy to start of IFNT'-interval, respectively. B7-H1 expression patterns did not correlate with survival. CONCLUSIONS: The SSIGN score demonstrated the best prognostic performance. In contrast, B7-H3 expression patterns showed a low association with histopathological parameters, but predicted the cut-off-dependent impaired survival and in the future may define a cut-off to indicate checkpoint-inhibitor treatment.

Perioperative morbidity, bowel function and oncologic outcome after radical cystectomy and ileal orthotopic neobladder reconstruction: Studer-pouch versus I-pouch.

OBJECTIVE: To investigate whether the length of ileum used for ileal orthotopic neobladder (ONB) reconstruction (60 cm vs. 40 cm) after radical cystectomy (RC) for bladder cancer (BC) impacts on bowel function, postoperative complications or survival outcome. MATERIAL AND METHODS: In this retrospective study, we included 56 patients who received an ONB (Studer (S)-Pouch: 23 patients; I-Pouch: 33 patients) after RC for BC between 2003 and 2011. Preoperative comorbidities were assessed by the Charlson Comorbidity Index (CCI) and surgical complications as graded by the Clavien-Dindo classification. Changes of perioperative bowel habits were retrospectively evaluated by the validated Gastrointestinal Quality of Life Index (GIQLI). Kaplan-Meier analyses calculated survival outcomes between both ONB types. RESULTS: Preoperative CCI was comparable between S- and I-pouch patients. No significant differences were observed for 30-day major- (p = 0.33) and minor (p = 0.96) complication rates between both neobladder types. S-Pouch patients reported higher preoperative stool frequencies (S-pouch: mean 2.7; I-pouch: mean 3.4; p = 0.049) and tended to suffer from urgency (S: mean 2.9; I: mean 3.4; p = 0.059). No significant differences in postoperative bowel disorders were found between both neobladder types (S-Pouch: 15.9, IQR; I-Pouch: 16.6 IQR; p = 0.84). Furthermore, we observed no overall-, cancer specific- or recurrence free survival advantage for either of both ONB variants (p = 0.81; 0.65 and 0.78), respectively. CONCLUSION: Comorbidities, perioperative complication rates and bowel habits were similar between both ONB substitutes and did not influence survival outcomes. These stratified data suggest that the length of ileum used for ONB reconstruction (60- vs. 40 cm) does not impact per se on postoperative bowel function.

Targeted vs systematic robot-assisted transperineal magnetic resonance imaging-transrectal ultrasonography fusion prostate biopsy.

OBJECTIVE: To evaluate the performance of transperineal robot-assisted (RA) targeted (TB) and systematic (SB) prostate biopsy in primary and repeat biopsy settings. PATIENTS AND METHODS: Patients underwent RA biopsy between 2014 and 2016. Before RA-TB, multiparametric magnetic resonance imaging (mpMRI) was performed. Prostate lesions were scored (Prostate Imaging, Reporting and Data System, version 2) and used for RA-TB planning. In addition, RA-SB was performed. Available, whole-gland pathology was analysed. RESULTS: In all, 130 patients were biopsy naive and 72 had had a previous negative transrectal ultrasonography-guided biopsy. In total, 202 patients had suspicious mpMRI lesions. Clinically significant prostate cancer was found in 85% of all prostate cancer cases (n = 123). Total and clinically significant prostate cancer detection rates for RA-TB vs RA-SB were not significantly different at 77% vs 84% and 80% vs 82%, respectively. RA-TB demonstrated a better sampling performance compared to RA-SB (26.4% vs 13.9%; P < 0.001). CONCLUSION: Transperineal RA-TB and -SB showed similar clinically significant prostate cancer detection rates in primary and repeat biopsy settings. However, RA-TB offered a 50% reduction in biopsy cores. Omitting RA-SB is associated with a significant risk of missing clinically significant prostate cancer.

The prognostic effect of salvage surgery and radiotherapy in patients with recurrent primary urethral carcinoma.

BACKGROUND: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC). PATIENTS: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48). RESULTS: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST). CONCLUSIONS: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment.

The thermoexpandable nitinol stent: a long-term alternative in patients without nephropathy or malignancy.

OBJECTIVE: The aim of this study was to investigate the long-term outcome of a thermoexpandable nickel-titanium nitinol ureteral stent (Memokath 051™) and to identify individual risk factors for failure. MATERIALS AND METHODS: This retrospective single-centre study included 125 patients who underwent implantation of the self-expandable Memokath 051 stent. Complications, indwelling time and reason for explantation were recorded. Analyses were stratified by gender, age, body mass index, American Society of Anesthesiologists score, estimated glomerular filtration rate (eGFR), side, localization and cause of the stricture. RESULTS: In total, 91 out of 125 patients (73%) were available for analysis. Median indwelling time was 355 days (range 7-2125 days). Most stents were removed because of dislocation (42%) or occlusion (40%). Stent removal was rarely performed because of infection (3%). Patients with sufficient renal function (eGFR ≥60 ml/min/1.73 m²) showed increased indwelling times compared with those with nephropathy (386 vs 317 days; p < 0.01). Patients with active malignant disease showed reduced patency time compared with strictures of benign origin (455 vs 190 days; p < 0.01). CONCLUSIONS: This thermoexpandable nitinol stent offers safe mid-term treatment of ureteric strictures, especially in patients without active malignancy and with good renal function.

Erratum: Large-field-of-view optical elastography using digital image correlation for biological soft tissue investigation (erratum).

[This corrects the article DOI: 10.1117/1.JMI.4.1.014505.].

Large-field-of-view optical elastography using digital image correlation for biological soft tissue investigation.

In minimally invasive surgery the haptic feedback, which represents an important tool for the localization of abnormalities, is no longer available. Elastography is an imaging technique that results in quantitative elastic parameters. It can hence be used to replace the lost sense of touch, as to enable tissue localization and discrimination. Digital image correlation is the chosen elastographic imaging technique. The implementation discussed here is clinically sound, based on a spectrally engineered illumination source that enables imaging of biological surface markers (blood vessels) with high contrast. Mechanical loading and deformation of the sample is performed using a rolling indenter, which enables the investigation of large organs (size of kidney) with reduced measurement time compared to a scanning approach. Furthermore, the rolling indentation results in strain contrast improvement and an increase in detection accuracy. The successful application of digital image correlation is first demonstrated on a silicone phantom and later on biological samples. Elasticity parameters and their corresponding four-dimensional distribution are generated via solving the inverse problem (only two-dimensional displacement field and strain map experimentally available) using a well-matched hyperelastic finite element model.

Comparison of different concepts for interpretation of chromosomal aberrations in urothelial cells detected by fluorescence in situ hybridization.

PURPOSE: Urine fluorescence in situ hybridization (FISH) has become a broadly used marker for noninvasive detection of bladder cancer (BC). However, it has been discussed whether the interpretation algorithm proposed by the manufacturer could be improved. Aim of the present study was to compare alternative evaluation strategies of FISH for detection of BC. METHODS: We included 1048 patients suspicious for BC, who underwent urine FISH examination before cystoscopy (diagnostic cohort). Herefrom, we selected 122 patients (prognostic cohort) with a history of non-muscle-invasive BC who were cystoscopically tumor free and received FISH analysis ahead of a follow-up period of 24 months. FISH results were interpreted by the algorithms of UroVysion™, Bubendorf et al. and Zellweger et al. RESULTS: In the diagnostic cohort, 228 patients (21.8%) had BC at time of evaluation; in the prognostic cohort 39 patients (32.0%) experienced tumor recurrence. Alterations in chromosome 3, 7 and 17 correlated with the presence of BC. Relative loss of 9p21 was associated with BC and higher risk for progression. The evaluation strategy proposed by Zellweger et al. showed highest accuracy of all FISH assessments. Performance of evaluation strategies differed in voided urine samples and samples obtained after mechanical manipulation. CONCLUSIONS: The performance of FISH in BC diagnosis strongly depends on the interpretation criteria. Alternative evaluation methods partly show superior diagnostic performance compared to the manufacturer's algorithm. The introduction of specific cutoffs for tetraploid cells improves specificity. Further modifications of the interpretation algorithm of the Urovysion® FISH assay have the potential to positively affect the value of this test in diagnosis and surveillance of BC.

Interdisciplinary consensus statement on indication and application of a hydrogel spacer for prostate radiotherapy based on experience in more than 250 patients.

BACKGROUND: The aim of the study was to reach a consensus on indication and application of a hydrogel spacer based on multicentre experience and give new users important information to shorten the learning curve for this innovative technique. METHODS: The interdisciplinary meeting was attended by radiation oncologists and urologists, each with experience of 23 - 138 hydrogel injections (SpaceOAR®) in prostate cancer patients before dose-escalated radiotherapy. User experience was discussed and questions were defined to comprise practical information relevant for successful hydrogel injection and treatment. Answers to the defined key questions were generated. Hydrogel-associated side effects were collected to estimate the percentage, treatment and prognosis of potential risks. RESULTS: The main indication for hydrogel application was dose-escalated radiotherapy for histologically confirmed low or intermediate risk prostate cancer. It was not recommended in locally advanced prostate cancer. The injection or implantation was performed under transrectal ultrasound guidance via the transperineal approach after prior hydrodissection. The rate of injection-related G2-toxicity was 2% (n = 5) in a total of 258 hydrogel applications. The most frequent complication (n = 4) was rectal wall penetration, diagnosed at different intervals after hydrogel injection and treated conservatively. CONCLUSIONS: A consensus was reached on the application of a hydrogel spacer. Current experience demonstrated feasibility, which could promote initiation of this method in more centres to reduce radiation-related gastrointestinal toxicity of dose-escalated IGRT. However, a very low rate of a potential serious adverse event could not be excluded. Therefore, the application should carefully be discussed with the patient and be balanced against potential benefits.

Oncological Outcomes of Patients with Concomitant Bladder and Urethral Carcinoma.

INTRODUCTION: The study aimed to investigate oncological outcomes of patients with concomitant bladder cancer (BC) and urethral carcinoma. METHODS: This is a multicenter series of 110 patients (74 men, 36 women) diagnosed with urethral carcinoma at 10 referral centers between 1993 and 2012. Kaplan-Meier analysis was used to investigate the impact of BC on survival, and Cox regression multivariable analysis was performed to identify predictors of recurrence. RESULTS: Synchronous BC was diagnosed in 13 (12%) patients, and the median follow-up was 21 months (interquartile range 4-48). Urethral cancers were of higher grade in patients with synchronous BC compared to patients with non-synchronous BC (p = 0.020). Patients with synchronous BC exhibited significantly inferior 3-year recurrence-free survival (RFS) compared to patients with non-synchronous BC (63.2 vs. 34.4%; p = 0.026). In multivariable analysis, inferior RFS was associated with clinically advanced nodal stage (p < 0.001), proximal tumor location (p < 0.001) and synchronous BC (p = 0.020). CONCLUSION: The synchronous presence of BC in patients diagnosed with urethral carcinoma has a significant adverse impact on RFS and should be an impetus for a multimodal approach.

Oncologic Impact of Renal Tissue Adjacent to Renal Cell Carcinoma.

AIM: The aim of the study was to investigate the clinical impact of the surgical margin width after nephron-sparing surgery (NSS) on the oncological course of renal cell carcinoma (RCC). PATIENTS AND METHODS: The study comprised of 126 RCC patients with NSS between 2002 and 2009. Inclusion criteria were negative resection margins and a tumor diameter of ≤100 mm with the possibility of a complete circumferential histopathological reevaluation. The minimal benign margin width was correlated to the patients' clinical course. RESULTS: Median safety margin width was revealed to be 1 mm. Nine of 126 patients (7.1%) developed recurrent disease (five local, four distant). All patients with local recurrence had safety margins ≤1 mm, whereas out of 49 patients with a margin >1 mm no one developed local recurrence (p=0.0245). Safety margin ≤1 mm showed associations with increased risk for overall recurrence in univariate and multivariate analysis (p=0.0531 and 0.0539, respectively). CONCLUSION: Tumor adjacent renal parenchyma may have oncological relevance, corroborating the need for further molecular investigation of tumor-adjacent tissue in RCC.