[68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

Impact of Preoperative LUTS on Health-related Quality of Life Following Radical Prostatectomy: A Propensity Score Matched Longitudinal Study.

OBJECTIVE: To assess the impact of preoperative lower urinary tract symptoms (LUTS) on long-term health-related quality of life (HRQOL) up to 10 years after radical prostatectomy (RP) for prostate cancer (PC). METHODS: Within our prospective institutional database of 6487 patients treated with RP for PC (2008-2020), 2727 patients with preoperative LUTS (IPSS score of ≥8) were identified. A 1:1 propensity-score matched analysis of 3056 men (n = 1528 LUTS, n = 1528 no LUTS) was conducted. Primary endpoint was HRQOL (based on EORTC QLQ-C30 and PR25). Linear regression models tested the effect of preoperative LUTS on the net change in general HRQOL (P <.05). RESULTS: Median follow-up was 48 months. Preoperative mean global health status (GHS) score (67.4 vs 75.7) was significantly lower in the LUTS cohort (P <.001). Post-RP the difference in general HRQOL between the LUTS cohort and the no-LUTS cohort became smaller (65.7 vs 67.8), however, remaining statistically significant (P = .037). In long-term follow-up, general HRQOL was comparable between both subcohorts (P-range 0.716-0.876). Multivariable linear regression analysis revealed increased preoperative IPSS as an independent predictor for increased perioperative improvement of IPSS (P <.001) CONCLUSION: For patients undergoing RP, preoperative LUTS were associated with a postoperative improvement of HRQOL outcomes. In long-term follow-up, HRQOL was comparable to patients without preoperative LUTS. Hence, RP is an efficient option to treat PC as well as LUTS in those patients.

The impact of previous inguinal mesh hernioplasty on oncological and patient-reported outcomes following radical prostatectomy.

BACKGROUND: The impact of previous inguinal mesh hernioplasty (MH) with non-resorbable mesh prostheses on surgical performance of radical prostatectomy (RP) has been controversially discussed, with unknown impact of MH on oncologic outcomes and health-related quality of life (HRQOL) following RP. We therefore aimed to assess the influence of previous MH on metastasis-free survival (MFS), biochemical recurrence-free survival (BRFS), and HRQOL following RP. METHODS: We identified 344 patients with previous MH prior RP within our prospectively assessed institutional database of 6275 patients treated with RP for PC (2008-2019). A 1:3 propensity-score matched analysis of 1345 men (n = 319 previous MH, n = 1026 no previous MH) was conducted. Primary endpoint was MFS and secondary endpoints were BRFS and HRQOL (based on EORTC QLQ-C30). Binary logistic regression, Kaplan-Meier, and Cox regression models tested the effect of previous MH on MFS, BRFS, and HRQOL (p < 0.05). RESULTS: Median follow-up was 47 months. Patients with previous MH had significantly lower 5-year MFS (72% vs. 85%, p < 0.001) and 5-year BRFS estimates (43% vs. 57%, p < 0.001). In multivariate analysis, previous MH was confirmed as an independent predictor for impaired MFS (hazard ratio [HR]: 3.772, 95% CI 1.12-12.64, p = 0.031) and BRFS (HR: 1.862, 95% CI: 1.22-2.85, p = 0.004). These results held true if stratified for surgical approach or limited to patients with successful PLND. We found significantly shorter median time to continence recovery for patients without previous MH (p = 0.001) without significant differences in total continence recovery rates, erectile function recovery, and HRQOL. CONCLUSIONS: Our findings show an impaired oncologic outcome for patients with previous MH following RP with no significant differences regarding continence recovery, erectile function recovery, and general HRQOL.

Associations of flow disruptions with patient, staff, and process outcomes: a prospective observational study of robotic-assisted radical prostatectomies.

BACKGROUND: Technological advancements in the operating room (OR) have sparked new challenges for surgical workflow, OR professionals, and patient safety. Disruptive events are frequent across all surgical specialties, but little is known about their effects on patient outcomes and the influence of systemic factors. The aim was to explore the associations of intraoperative flow disruptions (FDs) with patient outcomes, staff workload, and surgery duration. METHODS: Prospective, single-center, and multi-source study comprising direct and standardized OR observations of urologic surgical procedures, clinical patient outcomes, and staff- and patient-reported outcome data (PROMs; 3-month follow-up). All data were recorded between 01/2020 and 10/2021. FDs were assessed using standardized procedure observations. Linear and logistic regression analyses including multiple system factors were used to explore the effects of FDs on surgical outcomes. RESULTS: 61 robotic-assisted radical prostatectomy procedures were captured (with 61 patients and 243 staff reports). High rates of FDs were observed; however, our analyses did not show significant relationships with patient complication rates. Equipment- and patient-related FDs were associated with increased staff workload. No association was found between higher rates of FDs and procedure duration. CONCLUSIONS: FDs were not related to inferior patient outcomes. Our findings may inform future OR investigations that scrutinize the complex interplay of human, team, process, and technological components that mitigate the effects of FDs during surgery.

Absence of detrusor muscle in TUR-BT specimen - can we predict who is at highest risk?

INTRODUCTION: As a high-quality TUR-BT is important to ensure adequate treatment for bladder cancer patients, the aim of the current study is to investigate the impact of patient-related, surgical and tumor-specific parameters on detrusor muscle (DM) absence (primary objective) and to assess the impact of DM on the prognosis after a TUR-BT (secondary objective). PATIENTS AND METHODS: Transurethral resection of bladder tumors (TUR-BTs) between 2009 and 2021 were retrospectively screened (n = 3237). We included 2058 cases (1472 patients) for the primary and 472 patients for secondary objective. Clinicopathological variables including tumor size, localization, multifocality, configuration, operation time and skill-level of the urologist were assessed. We analyzed predictors for missing DM and prognostic factors for recurrence-free survival (RFS) for the complete cohort and subgroups. RESULTS: DM was present in 67.6% (n = 1371/2058). Surgery duration (continuous, minutes) was an independent predictor for absence of DM in the complete cohort (OR:0.98, r:0.012, 95%CI:0.98-0.99, p = 0.001). Other significant risk factors for missing DM were papillary tumors (OR:1.99, r:0.251, 95%CI:1.22-3.27, p = 0.006) in the complete cohort and bladder-roof and posterior-bladder-wall localization for re-resections. Absence of DM in high-grade BC correlated with reduced RFS (HR:1.96, 95%CI:1.0-3.79, p = 0.045). CONCLUSION: Sufficient time for a TUR-BT is mandatory to assure DM in the TUR-BT specimen. Also, cases with more difficult locations of bladder tumors should be performed with utmost surgical diligence and endourological training should incorporate how to perform such operations. Of note, DM correlates with improved oncological prognosis in high-grade BC.

Methylation status of various gene loci in localized prostate cancer: Novel biomarkers for diagnostics and biochemical recurrence.

BACKGROUND: Oncologic outcomes for patients with localized prostate cancer (PCa) undergoing radical prostatectomy (RP) can vary widely. Hypermethylation of tumor-associated genes has potential as a novel diagnostic tool and predictive biomarker in PCa. We investigated the methylation status of tumor-associated genes in patients who underwent RP. METHODS: Patients who underwent RP during 2004 to 2008 were matched retrospectively based on post-operative D'Amico risk stratification. Quantitative pyrosequencing was used to analyze methylation status of 10 gene loci in cancerous and adjacent benign tissue from histological specimen. Follow-up was performed according to EAU guideline recommendations. Statistical analyses were performed to correlate methylation levels in cancerous and benign tissue with risk profiles and biochemical recurrence (BCR). RESULTS: The cohort included 71 patients: 22 low-risk, 22 intermediate-risk, and 27 high-risk. Mean follow-up time was 74 months. Methylation status differed significantly between cancerous and adjacent benign tissue for the 5 gene loci GSTP1, APC, RASSF1, TNFRFS10c, and RUNX3 (each P < 0.001). Also, the methylation level was significantly higher in high-risk than in low-risk patients for Endoglin2 and APC (P = 0.026; P = 0.032). Using ROC analysis, hypermethylation of APC in PCa tissue was associated with higher risk of BCR (P = 0.005). CONCLUSION: Methylation status of various gene loci holds diagnostic and predictive potential in PCa. Hypermethylation of APC, RASSF1, TNFRFS10c and RUNX3 were identified as novel PCa-specific biomarkers. Furthermore, increased methylation levels of APC and Endoglin2 were associated with high-risk PCa. Additionally, hypermethylation of APC was associated with increased risk of BCR after RP.

Age and ECOG Performance Status as Predictors of Survival of Patients with Upper Urinary Tract Urothelial Carcinoma Undergoing Radical Nephroureterectomy.

INTRODUCTION: This study aimed to evaluate the impact of chronological and biological age on perioperative complications and survival after radical nephroureterectomy (RNU). Elderly patients with upper-tract urothelial carcinoma might be overtreated by RNU. METHODS: We retrospectively analyzed patients undergoing RNU. To evaluate the perioperative risk, patients were divided into four groups (<75; 75-79; 80-84; ≥85 years). The endpoints are perioperative complications and survival (overall survival [OS]). We calculated a risk score including chronological and biological age (Eastern cooperative oncology group performance status). Statistical analysis was performed by Kruskal-Wallis, Mann-Whitney U, χ2, log-rank, and Breslow tests. RESULTS: 194 patients were included in the study. Median follow-up was 25.5 months. Elderly cohorts ≥2 presented a higher number of days in intensive care unit following RNU (p < 0.001). Complication rates increased from cohort 1-4 with rates of 48.8%; 55.2%; 92.0%; 85.7% (p < 0.001). Median survival was 115, 55, 28, and 20 months for cohorts 1, 2, 3, and 4, respectively. The combined risk score revealed a significant 5-year OS benefit for patients with score 0 (82.3%) compared to score 1 (46.0%) and score 2 (15.0%; p < 0.001). DISCUSSION/CONCLUSION: We evaluated the impact of chronological and biological age on perioperative complications and survival after RNU. A combined risk score of chronological and biological age correlates with survival after RNU.

Ultrasound­New Techniques Are Extending the Applications.

BACKGROUND: Sonography is often the first imaging procedure to be used in diagnostic investigation of the abdomen. The aim of this article is to provide a new interdisciplinary overview of recent groundbreaking advances in this modality. METHODS: A selective survey of the literature in PubMed was conducted. The literature search was carried out in 2021-2022 and included publications over the period 2004-2022. RESULTS: The novel sonographic software techniques can be divided into algorithms that deal with conventional B-scan optimization and new programs that extend the scope of sonographic examination. The latter include elastography, contrast-enhanced sonography, and image fusion in combination with other cross-sectional imaging modalities. Elastography can be used to assess the presence of steatosis, fibrosis, or cirrhosis in patients with liver disease. One study reported diagnostic accuracy of 84-87% for the diagnosis of significant fibrosis (F2), 89-91% for the diagnosis of severe fibrosis (F3), and 92-93% for the diagnosis of liver cirrhosis (F4). Contrast-enhanced sonography is used for evaluation of tumors and trauma. A prospective multicenter study found sensitivity of 95.8% for the characterization of malignant lesions and specificity of 83.1% for benign lesions. Image fusion has the potential to improve the diagnostic assessment of parenchymatous organs, vascular conditions, and the prostate. CONCLUSION: With continuous improvement of the B-scan and the development of high-frequency probes and novel investigation techniques, sonography has become established as an increasingly autonomous examination procedure.

Operating room team strategies to reduce flow disruptions in high-risk task episodes: resilience in robot-assisted surgery.

In healthcare work settings, flow disruptions (FDs) pose a potential threat to patient safety. Resilience research suggests that adaptive behavioural strategies contribute to preventing cognitive overload through FDs at crucial moments. We aimed to explore the nature and efficacy of operating room (OR) team strategies to prevent FDs in robot-assisted surgery. Within a mixed-methods design, we first asked surgical professionals, which strategies they apply, and secondly, identified behavioural strategies through direct observations. Findings were analysed using content analysis. Additionally, FDs were assessed through live observations in the OR. The sample included four interviewed experts and 15 observed surgical cases. Sixty originally received strategies were synthesised into 17 final OR team strategies. Overall, 658 FDs were observed with external FDs being the most frequent. During high-risk episodes, FDs were significantly reduced (p < 0.0001). The identified strategies reveal how OR teams deliberatively and dynamically manage and mitigate FDs during critical tasks. Our findings contribute to a nuanced understanding of adaptive strategies to safeguard performance in robot surgery services. Practitioner Summary: Flow disruptions (FDs) in surgical work may become a severe safety threat during high-risk situations. With interviews and observations, we explored team strategies applied to prevent FDs in critical moments. We obtained a comprehensive list of behavioural strategies and found that FDs were significantly reduced during a specific high-risk surgical task. Our findings emphasise the role of providers' and teams' adaptive capabilities to manage workflow in high-technology care environments.

Development and Implementation of an Advanced Program for Robotic Treatment of Prostate Cancer-Is Surgical Quality Transferable?

Introduction: Robot-assisted radical prostatectomy (RARP) is a surgical treatment option for prostate cancer (PC). Quality in RARP depends on the surgeon´s operative volume and expertise. When implementing RARP, it is standard practice to hire a pre-trained surgeon. The aim of our study was to investigate the transferability of quality in RARP. Patients and Methods: We analyzed two consecutive retrospective cohorts of 100 and 108 men, respectively, who underwent RARP at two different centers and on whom surgery was performed by the same surgeon. Results: There were more men with high-grade PC in Cohort 1: 25/100 (25.0%) vs. 9/108 (8.3%), p < 0.01, and infiltration of the seminal vesicles was more frequent (23/100 (23.0%) vs. 10/108 (9.2%), p < 0.01). In Cohort 2, the duration of surgery was shorter and blood loss was lower: 149 (134−174) vs. 172 min (150−196), p < 0.01 and 300 (200−400) vs. 131 (99−188) mL, p < 0.01. No difference was found in the proportion of positive surgical margins in the T2 cohort (8.8% vs. 8.2%, p = 1.00). Conclusion: The procedural and oncological outcome parameters of Cohort 2 do not appear to be inferior to the results obtained for the first cohort. The quality of RARP is transferable if a pre-trained surgeon is hired.

The Burden of Fear of Cancer Recurrence in Genitourinary Cancers: A Prospective Study (NCT04535921).

INTRODUCTION: Fear of cancer recurrence (FCR) is a challenging and often unaddressed concern, and predictive factors for high FCR remain unclear. Therefore, the aim of the current study was to assess predictive factors for high FCR in patients undergoing surgery for genitourinary cancer. MATERIALS AND METHODS: Overall, 525 patients were prospectively included. FCR was measured using the validated FCR7 questionnaire prior to surgery and after receipt of the histological result. Family support, religiousness, quality-of-life impairment due to FCR, and distress were determined. Patient and tumor-related factors were compared with FCR levels using Mann-Whitney U test or Wilcoxon test. Multivariate analysis was performed by linear/binary regression. RESULTS: FCR after receipt of the final histology was significantly lower (median 13, range 6-34) than before surgery (median 15, range 6-36, p < 0.001). In univariate analysis, significant impact on preoperative FCR was observed for gender (p = 0.017), age (p = 0.002), working status (p = 0.038), and education (p = 0.002). High impairment of QoL was associated with higher FCR levels (p < 0.001). Comparing tumor-related factors with FCR, we observed significantly higher FCR scores in patients with nonorgan-confined disease (p = 0.011). CONCLUSION: This study is the first to describe FCR in patients with genitourinary cancers. Surgical treatment improves FCR. Sociodemographic factors like age, female gender, employment, and education were observed to influence FCR levels. Strong correlations between FCR, QoL, and psychological distress indicate the importance of further clinical screening for FCR. Tumor-related factors however seem to play a less prominent role.

Expression of Nectin-4 in Variant Histologies of Bladder Cancer and Its Prognostic Value-Need for Biomarker Testing in High-Risk Patients?

Variant histologies of bladder cancer (BC) often present with advanced tumor stage and the status of perioperative therapy is unclear. Thereby, squamous cell carcinoma (SCC), adenocarcinoma (ADENO), and sarcomatoid urothelial carcinoma (SARCO) are the most frequent variants. Nectin-4 has emerged as a highly interesting target in BC and might guide therapeutic application of antibody−drug conjugates (ADC). We therefore aimed to investigate expression patterns and prognostic value of Nectin-4 in variant histologies of BC. A single-center retrospective analysis was conducted of patients who underwent radical cystectomy (RC) for BC and revealed variant histologies of BC in the final specimens. Immunohistochemical staining for Nectin-4 was performed on tissue microarrays with 59 SCC, 22 ADENO, and 24 SARCO, and Nectin-4 expression was scored using the histochemical scoring system (H-score). Overall survival (OS) and progression-free survival (PFS) was calculated by Kaplan−Meier method. Median expression of Nectin-4 was 150 (range 0−250) in SCC, 140.5 (range 30−275) in ADENO, and 10 (0−185) in SARCO, with significantly lower levels for SARCO compared to SCC or ADENO (p < 0.001). For SCC, ADENO or SARCO no differences regarding OS or PFS were observed based on Nectin-4 expression levels (p > 0.05). Multivariate analysis revealed nodal stage as an independent prognostic factor for OS and PFS and metastases for PFS but not Nectin-4 expression. In conclusion, Nectin-4 was not prognostic in histological subtypes of BC in our study cohort. However, the high expression of Nectin-4 in SCC and ADENO might guide future treatment with novel Nectin-4-directed ADCs and provide this high-risk patient collective with a new promising therapeutic option. Testing Nectin-4 expression as a biomarker should be considered in trials with SARCO, where low Nectin-4 expression has been observed.

Outcomes and Prognostic Factors of Patients with Urothelial Carcinoma Undergoing Radical Cystectomy and pT0 in the Final Histology Without Neoadjuvant Chemotherapy.

Purpose: Absence of tumor in the final histopathology after radical cystectomy (RC) is a rare but potentially favorable outcome. Therefore, we aimed to analyze outcomes and prognostic factors of patients with urothelial carcinoma (UC) undergoing RC and T0 in the final histology without neoadjuvant chemotherapy at a high-volume academic center. Patients and Methods: We retrospectively analyzed patients undergoing RC for pure UC between 2004 and 2020. Cancer-specific survival (CSS) and overall survival (OS) were calculated using Kaplan-Meier analysis and group comparison by Log rank test. Potential prognostic factors were analyzed using univariate Cox regression models. Results: A total of 1051 patients with UC underwent RC. 72 patients (6.7%) showed pT0 in the final histology. Across all T-stages, 5-year CSS was significantly different with 88% for pT0, 80% for pTa/pTis, 78% for pT1, 76% for pT2, 51% for pT3 and 27% for pT4 in our cohort (p=0.001). Neither instillation therapy (HR 0.31, 95% CI 0.07-1.43), number of TURB prior RC (HR 1.47, 95% CI 0.25-6.18), use of photodynamic diagnostics (PDD) (HR 0.64, 95% CI 0.14-3.02), performing a second resection (HR 0.87, 95% CI 0.27-2.86), muscle-invasive disease prior RC at any TURB (HR 0.7, 95% CI 0.2-2.39) or muscle-invasive disease in the TURB prior RC (HR 1.0, 0.31-3.29) were associated with CSS in univariate analysis. Conclusion: pT0 reveals a survival benefit in patients undergoing RC for UC and therefore presents a distinctive tumor entity. As clinical and cystoscopic characteristics do not improve patient stratification, further research is warranted to define risk groups in this specific tumor entity.

Identification of the Tumor Infiltrating Lymphocytes (TILs) Landscape in Pure Squamous Cell Carcinoma of the Bladder.

Background: Tumor infiltrating lymphocytes (TILs) are known as important prognostic biomarkers and build the fundament for immunotherapy. However, the presence of TILs and its impact on outcome in pure squamous cell carcinoma (SCC) of the bladder remains uncertain. Methods: Out of 1600 patients undergoing radical cystectomy, 61 patients revealed pure bladder SCC in the final histopathological specimen. Retrospectively, immunohistochemical staining was performed on a subset of TILs (CD3+, CD4+, CD8+, CD20+). Endpoints were overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). The Kaplan−Meier method was used to evaluate survival outcomes. Results: Strong infiltration of CD3+ was found in 27 (44%); of CD4+ in 28 (46%); of CD8+ in 26 (43%); and of CD20+ in 27 tumors (44%). Improved OS was observed for strong CD3+ (p < 0.001); CD4+ (p = 0.045); CD8+ (p = 0.001); and CD20+ infiltration (p < 0.001). Increased rates of PFS were observed for CD3+ (p = 0.025) and CD20+ TILs (p = 0.002). In multivariate analyses, strong CD3+ (HR: 0.163, CI: 0.044−0.614) and strong CD8+ TILs (HR: 0.265, CI: 0.081−0.864) were revealed as predictors for OS and the strong infiltration of CD20+ cells (HR: 0.095, CI: 0.019−0.464) for PFS. Conclusions: These first results of TILs in bladder SCC revealed predictive values of CD3+, CD8+ and CD20+.

The Added Value of Baseline Health-Related Quality of Life in Predicting Survival in High-Risk Prostate Cancer Patients Following Radical Prostatectomy.

PURPOSE: Several studies have shown baseline health-related quality of life to be a valuable prognostic indicator of survival outcomes for various cancer entities in the metastatic setting. To date, there is no evidence regarding the prognostic value of baseline health-related quality of life for patients undergoing radical prostatectomy due to localized prostate cancer. MATERIALS AND METHODS: A total of 1,029 patients with high-risk prostate cancer according to National Comprehensive Cancer Network® risk stratification and prospectively assessed baseline health-related quality of life prior to radical prostatectomy were identified. Patients were stratified by global health status domain of the QLQ-C30 questionnaire. Oncologic endpoints were biochemical recurrence-free survival and metastasis-free survival. Multivariable Cox regression models were performed to assess prognostic significance of baseline global health status on survival outcomes. Harrell's discrimination C-index was applied to calculate the predictive accuracy of the model and previously described risk stratification models. Decision curve analysis was applied to test the clinical net benefit associated with adding global health status to our multivariable model (P < .05). RESULTS: Median follow-up was 43 months. In multivariable analysis, global health status was confirmed as an independent predictor for increased biochemical recurrence-free survival (HR .97, 95% CI .96-.99; P = .001) and metastasis-free survival (HR .96, 95% CI .93-.99; P = .013), indicating a relative risk reduction of 2.9% for biochemical recurrence-free survival and 3.7% for metastasis-free survival per 1-point increase of baseline global health status. Adding baseline health-related quality of life to our model and to the Cancer of the Prostate Risk Assessment and National Comprehensive Cancer Network score improved discrimination in predicting biochemical recurrence-free survival and metastasis-free survival of the respective models. Decision curve analysis revealed a net benefit over all threshold probabilities. CONCLUSIONS: Our findings highlight baseline health-related quality of life to be a valuable and robust prognostic factor for patients with localized high-risk prostate cancer prior to radical prostatectomy. Baseline health-related quality of life increased prognostic accuracy of biochemical recurrence-free survival and metastasis-free survival.

Accuracy and prognostic value of radiological lymph node features in variant histologies of bladder cancer.

PURPOSE: To provide first evidence of lymph node (LN) staging using CT scan and its prognostic value in variant histologies of bladder cancer. This knowledge may optimize patient management with variant histologies based on CT morphological findings. METHODS: Preoperative CT scans of patients with variant histologies who underwent RC between 2004 and 2019 were reanalyzed by two independent radiologists in a blinded review process. Specificity, sensitivity, and accuracy for LN staging as well as LN characteristics were evaluated. Correlation with survival was investigated by Kaplan-Meier method, log-rank test and multivariate analysis. RESULTS: 1361 patients with primary tumor of the bladder underwent RC, of which 163 (12%) patients revealed variant histologies. 65 (47.8%) patients have shown an urothelial variant (UV) and 71 (52.2%) a non-urothelial variant (NUV). LN metastases were found in 18 (27.7%) patients with UV and 21 (29.6%) patients with NUV. The accuracy to detect LN metastasis for all variant histologies was 62% with a sensitivity of 46% and a specificity of 70%. Subgroups of UV and NUV revealed an accuracy of 67% and 57%. An increased number of regional LN (HR 2.8; 1.34-6.18) and the loss of fatty hilum (HR 0.36, 0.17-0.76) were prognostic parameters. In multivariate analysis, a fatty hilum (HR 0.313, 0.104-0.945) and the presence of lymph node metastases (HR 2.866, 1.140-7.207) were prognostic. CONCLUSION: This first study on CT morphological behavior of variant histologies revealed an accuracy of UV and NUV comparable to UC with low specificity for all variant histologies. CT scan prior RC should be interpreted in regard to histological subtypes.

Long-term Health-related Quality of Life (HRQOL) After Radical Cystectomy and Urinary Diversion - A Propensity Score-matched Analysis.

INTRODUCTION: Radical cystectomy (RC) and urinary diversion by ileal conduit (IC) or ileal orthotopic neobladder (ONB) is the standard-of-care for surgical treatment of muscle-invasive bladder cancer. Yet, it is unclear how urinary diversion affects the patient's health-related quality of life (HRQOL) in the longer-term. METHODS: HRQOL was assessed preoperatively, 3mo postoperatively and then annually until a maximum follow-up of 48 months using the validated EORTC QLQ-C30- as well as the bladder cancer-specific FACT-BL- and QLQ-BLM30-questionnaires. A propensity-score matching for the variables "age," "ASA-classification," "cardiovascular co-morbidity," "sex" as well as "tumor stage," and "preoperative physical functioning score" was performed. Hypothetical predictors for decreased general HRQOL were analyzed using multivariable logistic regression models. RESULTS: After propensity-score matching, 246 patients were analyzed. HRQOL assessment revealed significant differences regarding preoperative QLQ-C30 symptoms which diminished during the postoperative time course. Similarly, we did not find significant differences based on bladder cancer-specific FACT-BL and QLQ-BLM HRQOL assessment including body image (48 months: 29.6.4 [IC] vs. 40.7 [ONB]; P = .733). Regarding general HRQOL, we found increased global health status scores for ONB throughout the whole observational period without reaching statistical significance (48 months: 55.0 [IC] vs. 70.1 [ONB]; P = .079). In multivariate analysis, cardiovascular comorbidity was an independent predictor of impaired HRQOL 24 months (HR 2.20; CI95% 1.02-5.72, P = .044) and 36 months (HR 6.84; CI95% 1.61-29.14, P = .009) postoperatively. CONCLUSION: We did not observe significant differences in bladder-specific as well as generic HRQOL in the longer-term and consequently, the type of urinary diversion was not an independent predictor of good general HRQOL in a follow-up period of 4 years.

Baseline Health-related Quality of Life Predicts Bladder Cancer-specific Survival Following Radical Cystectomy.

BACKGROUND: It has been shown that baseline health-related quality of life (HRQOL) is a valuable prognostic indicator of survival outcomes for various metastatic cancers, but there is no evidence on the prognostic value of baseline HRQOL for patients with bladder cancer undergoing radical cystectomy (RC) and ileal conduit (IC) or orthotopic ileal neobladder (ONB) with curative intent. OBJECTIVE: To assess the association between baseline HRQOL and survival outcomes following RC. DESIGN, SETTING, AND PARTICIPANTS: The study included 407 patients with prospectively assessed baseline HRQOL before RC. Patients were stratified according to the Global Health Status (GHS) domain of the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire, with good general HRQOL defined as GHS ≥70 on the basis of validated cutoff levels. A propensity score-matched analysis of 357 patients (1:2 ratio; 125 patients with GHS ≥70 vs 232 with GHS <70) was performed. INTERVENTION: RC with IC or ONB. OUTCOME MEASURES AND STATISTICAL ANALYSIS: The primary endpoint was cancer-specific survival (CSS). The secondary endpoints were overall survival (OS) and recurrence-free survival (RFS). Kaplan-Meier and multivariate Cox regression models were constructed to assess the prognostic value of baseline GHS for prediction of survival outcomes. RESULTS AND LIMITATIONS: Median follow-up was 40.5 mo. The rates of 5-yr CSS (82% vs 65%; p = 0.001), 5-yr OS (76% vs 53%; p = 0.001), and 5-yr RFS (50% vs 39%; p = 0.04) were significantly higher in the GHS ≥70 cohort. GHS ≥70 was confirmed as an independent predictor for CSS (hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.18-0.73; p = 0.004), OS (HR 0.45, 95% CI 0.26-0.79; p = 0.005), and RFS (HR 0.50, 95% CI 0.30-0.83; p = 0.008) in multivariate analyses. Study limitations include the retrospective analysis of prospectively collected data and use of a HRQOL questionnaire not specifically for bladder cancer. CONCLUSIONS: Our findings suggest that preoperative baseline HRQOL has significant predictive value for outcomes of RC with curative intent for bladder cancer. We found that good general HRQOL at baseline accurately predicts greater CSS, OS, and RFS. PATIENT SUMMARY: We assessed the association between health-related quality of life at baseline and survival outcomes after radical cystectomy for bladder cancer. We found that good general health-related quality of life at baseline predicts better survival outcomes and that higher baseline scores were associated with greater cancer-specific survival.

Prognostic Value of Pretreatment Inflammatory Markers in Patients Receiving Radical Cystectomy for Urothelial Bladder Cancer: Does Age Matter?

INTRODUCTION: Biomarkers are known predictors for survival after radical cystectomy (RC) and can improve patient stratification. Yet, it remains unclear how age influences their prognostic value. The current study aimed to assess the impact of age on standard prognostic biomarkers in different age-groups. MATERIALS AND METHODS: Overall, 1,014 patients undergoing RC for bladder cancer were included. Patients were divided into age-groups (I - <60, II - 60-69, III - 70-79, and IV - ≥80). C-reactive protein (CRP), hemoglobin (Hb), thrombocytes, and leucocytes prior to RC were used as biomarkers. The Kaplan-Meier method and log-rank test were used to compare overall survival (OS) and cancer-specific survival (CSS). For independent predictors of survival, multivariate models were applied. RESULTS: Absolute levels of biomarkers except CRP revealed a significant decrease with increasing age. We found low Hb to be associated with impaired CSS in groups II (2.05 [1.32-3.17]; p = 0.001), III (2.83 [2.01-4.00]; p < 0.001), and IV (1.79 [1.12-2.84]; p = 0.014). Thrombocytes above the cutoff were associated with impaired CSS and OS in groups II, III, and IV for CSS and OS. Leukocytes were associated with impaired CSS and OS in group II (2.11 [1.38-3.23]; p < 0.001 and 1.99 [1.36-2.90]; p < 0.001) and III (1.70 [1.08-2.67]; p = 0.021 and 1.80 [1.25-2.58]; p = 0.002). Elevated CRP was associated with impaired CSS and OS across all groups. CONCLUSION: Biomarkers are predictors for survival after RC. Yet, their impact on survival is less in the oldest patient group. Therefore, careful patient stratification and treatment administration should be considered in elderly patients. Further investigations are needed to fully understand the underlying mechanisms.

Clinical Implication of Borderline CT-Morphological Metastatic Spread in Bladder Cancer: What You See Is Not Always What You Got.

INTRODUCTION: Palliative radical cystectomy (pRC) may be offered to selected bladder cancer (BC) patients with grievous local symptoms. However, there is only scarce information on perioperative complications and prognosis, especially in the case of metastatic spread. We intended to analyze morbidity and oncological outcome in this patient subgroup. MATERIALS: Patients undergoing pRC because of BC with radiologic evidence of metastases were included in this retrospective study. Perioperative adverse events (AEs) were graded by the Clavien-Dindo Classification system. All patients underwent CT-based surveillance, and questionnaires were sent for survival follow-up in predefined intervals. Oncological outcome and predictive markers were assessed in univariate and multivariate analyses, using log-rank tests and Cox-regression analyses. RESULTS: Between 2004 and 2016, 77 patients were identified. Median age at surgery was 70 years (IQR 66-77) and the median follow-up time was 12 months (IQR 4-44). Preoperative staging revealed pulmonary, hepatic, bone, peritoneal, and various other metastasis in 46/77 (60%), 14/77 (18%), 11/77 (14%), 5/77 (7%), and 11/77 (14%) cases, respectively. Most frequently observed symptoms at the time of pRC were severe gross hematuria (n = 41) and intense pain (n = 11). Most AEs were of minor grade (83%). The median length of stay was 20 days. Median CSS was 13 months with a 5-year CSS of 34%. Intriguingly and unsuspectedly, preoperatively suspicious lung lesions were confirmed during surveillance only in 33%, respectively. In multivariate analysis, intraoperative blood transfusions (HR = 2.25, 95% CI: 1.09-4.63, p = 0.028) were significantly associated with decreased CSS. The best outcome was observed in patients with only subpleural metastases (CSS 80 months, p = 0.039) and normal CRP- and Hb values. CONCLUSION: pRC can be performed with acceptable perioperative morbidity and mortality. Pulmonary lesions seem to have a risk of false-positive results and should be biopsied in all uncertain cases. Localization of lung metastases together with preoperative CRP- and Hb levels seem to play a prognostic role.