The prognostic value of perioperative platelet and leukocyte values in patients undergoing radical cystectomy: a prospective long-term cohort study.

INTRODUCTION: Studies assessing the impact of preoperative and first-day postoperative values of leukocytes, thrombocytes, and platelet/leukocyte ratio (PLR) after radical cystectomy (RC) are sparse. We aimed to assess the impact of these factors on long-term survival after RC. METHODS: An analysis of patients undergoing open RC from 2004 to 2023 at our center was performed. Leukocytosis was defined as ≥8,000 leukocytes/µL and thrombocytosis as ≥400,000 thrombocytes/µL. Similarly, the cutoff for PLR was set at 28. A multivariable Cox regression analysis was performed to assess the role of leukocytosis, thrombocytosis and PLR on long-term survival after RC. For all analyses hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,817 patients with a median age of 70 years (IQR: 62-77) were included. Overall, 804 (44%), 175 (10%), and 1,296 (71%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 preoperatively. Accordingly, 1,414 (78%), 37 (2%), and 249 (14%) patients presented with leukocytosis, thrombocytosis, and PLR ≥28 on the first day after RC. At a median follow-up of 26 months (IQR: 8-68) after RC, 896 (49%) patients died. In the multivariate Cox regression analysis after adjusting for major perioperative risk factors, only preoperative leukocytosis (HR: 1.3, 95%CI: 1.1-1.6, p=0.01), as well as both preoperative and first-day thrombocytosis (HR: 2.1, 95%CI: 1.5-2.9 and HR: 2.8, 95%CI: 1.6-5.1, p<0.001, accordingly) were associated with worse overall survival. CONCLUSION: PLR should not be used as a prognostic marker for survival after RC. On the contrary, preoperative leukocytosis, as well as preoperative and first-day thrombocytosis should raise awareness among clinicians performing RC, since they were independently associated with worse survival after RC.

Impact of preoperative LUTS on Health-Related Quality of Life following Radical Prostatectomy - A propensity score matched longitudinal study.

OBJECTIVES: 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<0.05). 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<0.001). 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=0.037). 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<0.001) CONCLUSIONS: 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.

Health-related quality of life following salvage radical prostatectomy for recurrent prostate cancer after radiotherapy or focal therapy.

BACKGROUND: Salvage radical prostatectomy (sRP) is an important treatment option for patients with recurrent prostate cancer (PCa) after radiotherapy (RT) or focal therapy (FT). However, health-related quality of life (HRQOL) after sRP depending on the primary treatment is understudied. METHODS: Patients who underwent Salvage RP for recurrent PCa were analyzed. The primary outcome of this study was HRQOL assessed by the quality-of-life questionnaire (QLQ)-C30 and its prostate specific QLQ-PR25 add-on. Secondary outcomes were functional outcome parameters (erectile function, continence) and biochemical recurrence-free survival (BRFS). Statistical analyses employed the chi-square test, Mann-Whitney U test, and Kaplan-Meier method, with a p value < 0.05 denoting significance. RESULTS: 37 patients with RT as primary treatment (RT-sRP) and 22 patients with focal therapy prior sRP (FT-sRP) were analyzed. Mean global health score was not significantly different preoperatively (71.9 vs. 67.3, p = 0.89) as well as after a median of 32 months follow-up (54.9 vs. 50.6, p = 0.63) with impaired HRQOL after sRP in both groups. Baseline erectile dysfunction was more prevalent in the RT-sRP group (mean IIEF-5: 5.0) than in the FT-sRP group (mean IIEF-5: 8.5, p = 0.037). No differences were observed at follow-up for erectile function (IIEF-5-Score: 0.5 vs 2.5, p = 0.199) and continence (continence rate: 48.4% vs 52.9% (p = 0.763) between the RT-sRP and FT-sRP group. 5-year-BRFS was 60% (RT-sRP) and 68% (FT-sRP, p = 0.849). CONCLUSIONS: sRP impacts HRQOL in patients with PCa after RT and FT with no significant differences. Comparison with HRQOL and BRFS of treatment alternatives is paramount to counsel patients for appropriate treatments.

The impact of perioperative risk factors on long-term survival after radical cystectomy: a prospective, high-volume cohort study.

INTRODUCTION: Radical cystectomy (RC) is the gold standard for muscle-invasive bladder cancer. Nevertheless, RC is associated with substantial perioperative morbidity and mortality. We aimed to evaluate the role of important perioperative risk factors in predicting long-term survival after RC. METHODS: An analysis of the prospective cohort of patients undergoing open RC from 2004 to 2023 at our center was performed. Patients who died within one month after RC were excluded from the study. A univariate and multivariable Cox regression analysis was performed to assess the role of sex, age, urinary diversion, preoperative values of creatinine and hemoglobin, first-day postoperative values of CRP, leucocytes, and thrombocytes, perioperative Clavien-Dindo complications, perioperative chemotherapy, admission to the intensive or intermediate care unit, as well as type of histology, pathologic T-stage, positive lymph nodes, and positive surgical margins on predicting the long-term overall survival after RC. For all analyses hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) were estimated. RESULTS: A total of 1,750 patients with a median age of 70 years (IQR: 62-76) were included. Of them, 1,069 (61%) received ileal conduit and 650 (37%) neobladder. Overall, 1,016 (58%) perioperative complications occurred. At a median follow-up of 31 months (IQR: 12-71), 884 (51%) deaths were recorded. In the multivariable Cox regression analysis, increasing age (HR: 1.03, 95%CI: 1.02-1.04, p < 0.001), higher preoperative creatinine values (HR: 1.27, 95%CI: 1.12-1.44, p < 0.001), lower preoperative hemoglobin values (HR: 0.93, 95%CI: 0.89-0.97, p = 0.002), higher postoperative thrombocyte values (HR: 1.01, 95%CI: 1.01-1.02, p = 0.02), Clavien-Dindo 1-2 complications (HR: 1.26, 95%CI: 1.03-1.53, p = 0.02), Clavien-Dindo 3-4 complications (HR: 1.55, 95%CI: 1.22-1.96, p < 0.001), locally advanced bladder cancer (HR: 1.29, 95%CI: 1.06-1.55, p = 0.009), positive lymph nodes (HR: 1.74, 95%CI: 1.45-2.11, p < 0.001), and positive surgical margins (HR: 1.61, 95%CI: 1.29-2.01, p < 0.001) negatively affected long-term survival. CONCLUSION: Beside increased age and worse oncological status, impaired renal function, lower preoperative hemoglobin values, higher postoperative thrombocyte values, and perioperative complications are independent risk factors for mortality in the long term in patients undergoing open RC.

Patients' Trust in Artificial Intelligence-based Decision-making for Localized Prostate Cancer: Results from a Prospective Trial.

BACKGROUND: Artificial intelligence (AI) has the potential to enhance diagnostic accuracy and improve treatment outcomes. However, AI integration into clinical workflows and patient perspectives remain unclear. OBJECTIVE: To determine patients' trust in AI and their perception of urologists relying on AI, and future diagnostic and therapeutic AI applications for patients. DESIGN, SETTING, AND PARTICIPANTS: A prospective trial was conducted involving patients who received diagnostic or therapeutic interventions for prostate cancer (PC). INTERVENTION: Patients were asked to complete a survey before magnetic resonance imaging, prostate biopsy, or radical prostatectomy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was patient trust in AI. Secondary outcomes were the choice of AI in treatment settings and traits attributed to AI and urologists. RESULTS AND LIMITATIONS: Data for 466 patients were analyzed. The cumulative affinity for technology was positively correlated with trust in AI (correlation coefficient 0.094; p = 0.04), whereas patient age, level of education, and subjective perception of illness were not (p > 0.05). The mean score (± standard deviation) for trust in capability was higher for physicians than for AI for responding in an individualized way when communicating a diagnosis (4.51 ± 0.76 vs 3.38 ± 1.07; mean difference [MD] 1.130, 95% confidence interval [CI] 1.010-1.250; t924 = 18.52, p < 0.001; Cohen's d = 1.040) and for explaining information in an understandable way (4.57 ± vs 3.18 ± 1.09; MD 1.392, 95% CI 1.275-1.509; t921 = 27.27, p < 0.001; Cohen's d = 1.216). Patients stated that they had higher trust in a diagnosis made by AI controlled by a physician versus AI not controlled by a physician (4.31 ± 0.88 vs 1.75 ± 0.93; MD 2.561, 95% CI 2.444-2.678; t925 = 42.89, p < 0.001; Cohen's d = 2.818). AI-assisted physicians (66.74%) were preferred over physicians alone (29.61%), physicians controlled by AI (2.36%), and AI alone (0.64%) for treatment in the current clinical scenario. CONCLUSIONS: Trust in future diagnostic and therapeutic AI-based treatment relies on optimal integration with urologists as the human-machine interface to leverage human and AI capabilities. PATIENT SUMMARY: Artificial intelligence (AI) will play a role in diagnostic decisions in prostate cancer in the future. At present, patients prefer AI-assisted urologists over urologists alone, AI alone, and AI-controlled urologists. Specific traits of AI and urologists could be used to optimize diagnosis and treatment for patients with prostate cancer.

Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

The Impact of Laser Energy on Functional Outcome Following Holmium Laser Enucleation of the Prostate.

OBJECTIVE: To assess the impact of total laser energy applied, as well as enucleation efficiency on short-term functional outcomes for patients treated for lower urinary tract symptoms (LUTS) with Holmium laser enucleation of the prostate (HoLEP). METHODS: A retrospective analysis of 1593 consecutive patients who underwent HoLEP for LUTS due to benign prostate obstruction in a tertiary care center between January 2018 and January 2021 was performed. Perioperative parameters and short-term functional outcome were evaluated. Spearman's rank correlation and linear regression analysis was applied to identify the relationship between total laser energy applied or enucleation efficiency and functional outcome (P < .05). RESULTS: Median weight of enucleated tissue was 65g, median tissue retrieval percentage was 72.2% and median surgery speed was 0.8g/min. Median laser energy applied was 48.8 kJ, median enucleation efficiency was 1.4g/kJ. No significant correlation between the total laser energy and postoperative International Prostate Symptom Score (IPSS), peak urinary flow (Qmax) or postvoid residual urine volume (PVR) was found (P-range: .473-.969). Likewise, no correlation was found between enucleation efficiency and postoperative IPSS, Qmax, and PVR (P-range: .080-.932). Perioperative improvement of functional outcome (delta IPSS, delta Qmax, and delta PVR) did not correlate with total laser energy applied (P-range: .211-.785) or with enucleation efficiency (P-range: .118-.543). Those results were confirmed in linear regression analysis. CONCLUSION: The results of this study reveal that functional outcome following HoLEP are not dependant on the amount of laser energy applied or enucleation efficiency. Our results should support the increased use of HoLEP as surgical treatment option for LUTS due to BPH.

A Systematic Review of New Imaging Technologies for Robotic Prostatectomy: From Molecular Imaging to Augmented Reality.

New imaging technologies play a pivotal role in the current management of patients with prostate cancer. Robotic assisted radical prostatectomy (RARP) is a standard of care for localized disease and through the already imaging-based console subject of research towards combinations of imaging technologies and RARP as well as their impact on surgical outcomes. Therefore, we aimed to provide a comprehensive analysis of the currently available literature for new imaging technologies for RARP. On 24 January 2023, we performed a systematic review of the current literature on Pubmed, Scopus and Web of Science according to the PRISMA guidelines and Oxford levels of evidence. A total of 46 studies were identified of which 19 studies focus on imaging of the primary tumor, 12 studies on the intraoperative tumor detection of lymph nodes and 15 studies on the training of surgeons. While the feasibility of combined approaches using new imaging technologies including MRI, PSMA-PET CT or intraoperatively applied radioactive and fluorescent dyes has been demonstrated, the prospective confirmation of improvements in surgical outcomes is currently ongoing.

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.

Oncologic Outcomes of Lymph Node Dissection at Salvage Radical Prostatectomy.

BACKGROUND: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. OBJECTIVE: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. PATIENTS AND METHODS: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan-Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). CONCLUSIONS: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

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.

An Analysis of the Distribution of PSMA PET/CT-Positive Lymph Nodes and Their Coverage by Different Elective Nodal Radiation Volumes in Postoperative Prostate Cancer Patients.

Salvage elective nodal radiotherapy (ENRT) is a treatment option for patients with biochemically persistent or recurrent prostate cancer who have lymph node metastases (LNs) after prostatectomy. Possible ENRT templates were proposed by the Radiation Therapy Oncology Group (RTOG; 2009), the PIVOTAL trialists (2015), and the NRG Oncology Group (2021). The goal of this study was to analyze the distribution of prostate-specific membrane antigen (PSMA) PET/CT-positive LNs and to compare the templates regarding their LN coverage. Methods: We analyzed the PSMA PET/CT scans of 105 patients with PET-positive LNs treated with salvage ENRT from 2014 to 2019. All LNs were mapped in an exemplary dataset, classified by region, and assessed with regard to their potential coverage by the 3 ENRT templates. The primary endpoint was the number of missed LNs. The secondary endpoint was the number of patients with full coverage. To compare the templates, a t test and McNemar test were used. Results: Three hundred thirty-five LNs were contoured (3.19 per patient; 95% CI, 2.43-3.95). Most frequently, LNs were seen in the internal iliac (n = 94, 28.1%), external iliac (n = 60, 17.9%), periaortic (n = 58, 17.3%), common iliac (n = 55, 16.4%), perirectal (n = 26, 7.8%), and presacral (n = 19, 5.7%) regions. The NRG template missed fewer LNs per patient (1.01, 31.7%) than the RTOG (1.28, 40.1%, P < 0.001) and PIVOTAL templates (1.19, 37.3%, P = 0.003). No difference was observed in the number of patients with full coverage of all LNs: 52 (49.5%) with the NRG template versus 50 (47.6%) with the RTOG (P = 0.625) and 49 (46.7%) with the PIVOTAL template (P = 0.250). Conclusion: The NRG template showed better coverage than the RTOG and PIVOTAL templates. Nevertheless, in this cohort, it would have missed almost one third of all contoured LNs and would have resulted in incomplete coverage in half the patients. This result underlines the importance of advanced imaging, such as PSMA PET/CT scans, before salvage ENRT and shows the need for further individualization of ENRT fields.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer Following First-line Nonsurgical Treatment: Validation of the European Association of Urology Criteria in a Large, Multicenter, Contemporary Cohort.

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000-2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen-free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13-2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. PATIENT SUMMARY: We looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria.

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.