Differences in overall survival of penile cancer patients versus population-based controls.

PURPOSE: To assess whether 5-year overall survival (OS) of squamous cell carcinoma of the penis (SCCP) patients differs from age-matched male population-based controls. METHODS: We relied on the Surveillance Epidemiology and End Results database (2004-2018) to identify newly diagnosed (2004-2013) SCCP patients. For each case, we simulated an age-matched control (Monte Carlo simulation), relying on the Social Security Administration (SSA) Life Tables with 5 years of follow-up. We compared OS between SCCP patients and population-based controls in a stage-specific fashion. Smoothed cumulative incidence plots displayed cancer-specific mortality (CSM) versus other-cause mortality (OCM). RESULTS: Of 2282 SCCP patients, the stage distribution was as follows: stage I 976 (43%) versus stage II 826 (36%) versus stage III 302 (13%) versus stage IV 178 (8%). At 5 years, OS of SCCP patients versus age-matched population-based controls was as follows: stage I 63% versus 80% (Δ = 17%), stage II 50% versus 80% (Δ = 30%), stage III 39% versus 84% (Δ = 45%), stage IV 26% versus 87% (Δ = 61%). At 5 years, CSM versus OCM in SCCP patients according to stage was as follows: stage I 12% versus 24%, stage II 22% versus 28%, stage III 47% versus 14%, and stage IV 60% versus 14%. CONCLUSION: SCCP patients exhibit worse OS across all stages. The difference in OS at 5 years between SCCP and age-matched male population-based controls ranged from 17% to 61%. At 5 years, CSM accounted for 12% to 60% of all deaths, across all stages.

Human Tularemia Epididymo-Orchitis Caused by Francisella tularensis Subspecies holartica, Austria.

A previously healthy man in Austria had tularemia epididymo-orchitis develop, leading to unilateral orchiectomy. Francisella tularensis subspecies holartica was detected by 16S rRNA gene sequencing analysis of inflamed granulomatous testicular tissue. Clinicians should suspect F. tularensis as a rare etiologic microorganism in epididymo-orchitis patients with relevant risk factors.

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.

MiR-371a-3p Serum Levels Are Increased in Recurrence of Testicular Germ Cell Tumor Patients.

Metastatic testicular germ cell tumors (TGCTs) are a potentially curable disease by administration of risk-adapted cytotoxic chemotherapy. Nevertheless, a disease-relapse after curative chemotherapy needs more intensive salvage chemotherapy and significantly worsens the prognosis of TGCT patients. Circulating tumor markers (ß-subunit of human chorionic gonadotropin (ß-HCG), alpha-Fetoprotein (AFP), and Lactate Dehydrogenase (LDH)) are frequently used for monitoring disease recurrence in TGCT patients, though they lack diagnostic sensitivity and specificity. Increasing evidence suggests that serum levels of stem cell-associated microRNAs (miR-371a-3p and miR-302/367 cluster) are outperforming the traditional tumor markers in terms of sensitivity to detect newly diagnosed TGCT patients. The aim of this study was to investigate whether these miRNAs are also informative in detection of disease recurrence in TGCT patients after curative first line therapy. For this purpose, we measured the serum levels of miR-371a-3p and miR-367 in 52 samples of ten TGCT patients at different time points during disease relapse and during salvage chemotherapy. In our study, miR-371a-3p levels in serum samples with proven disease recurrence were 13.65 fold higher than levels from the same patients without evidence of disease (p = 0.014). In contrast, miR-367 levels were not different in these patient groups (p = 0.985). In conclusion, miR-371a-3p is a sensitive and potentially novel biomarker for detecting disease relapse in TGCT patients. This promising biomarker should be investigated in further large prospective trials.

Critical evaluation of the potential prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio under consideration of C-reactive protein levels in clear cell renal cell carcinoma.

BACKGROUND: We investigated the prognostic value of the pretreatment-derived neutrophil-lymphocyte ratio (dNLR) and original NLR in relation to the commonly used inflammation marker C-reactive protein (CRP) in a large cohort of patients with clear cell renal cell carcinoma (RCC). METHODS: Clinicopathological data from 587 consecutive non-metastatic clear cell RCC patients, operated between 2000 and 2010 at a single tertiary academic center, were evaluated retrospectively. Patients were categorised according to a cutoff value derived from receiver operating curve analysis. Overall (OS), cancer-specific (CSS) as well as metastasis-free survival (MFS) were assessed using the Kaplan-Meier method and multivariate Cox proportional models were applied. Spearman's rank correlation coefficient tested the association between dNLR and other markers of the systemic inflammatory response. RESULTS: The significant correlation between pretreatment NLR and dNLR was strong (ρ=0.84), whereas between dNLR and CRP it was weak (ρ=0.18). In multivariate analyses, dNLR achieved independent predictor status regarding CSS (P=0.037) and MFS (P=0.041), whereas CRP was confirmed as independent predictor of OS (P=0.010), CSS (P=0.039) and MFS (P=0.005), respectively. The NLR failed to reach independent predictor status regarding OS, CSS and MFS when CRP was included into the multivariate model. CONCLUSIONS: In the cohort studied, an elevated (⩾10.0) pretreatment CRP level and elevated dNLR (>2) were robust independent predictors of CSS and MFS. Our data suggest that CRP might be superior to both NLR and dNLR.

Blood Platelet Volume Represents a Novel Prognostic Factor in Patients with Nonmetastatic Renal Cell Carcinoma and Improves the Predictive Ability of Established Prognostic Scores.

PURPOSE: The average size of blood platelets determined by mean platelet volume might represent a biologically meaningful parameter in carcinogenesis and potentially serve as a novel prognostic biomarker in renal cell carcinoma. MATERIALS AND METHODS: In this retrospective analysis of the records of 652 patients we evaluated the potential prognostic value of mean platelet volume and its ability to improve existing risk assessment tools used in adjuvant clinical trials in nonmetastatic renal cell carcinoma cases. Associations of mean platelet volume with baseline covariates and clinical outcomes (recurrence, and death from renal cell carcinoma and other causes) were assessed with the competing risk estimators of Kaplan-Meier, and Marubini and Valsecchi, respectively. Univariable and multivariable Cox proportional hazard models were constructed. The Harrell c-index was applied to test improvements in the predictive accuracy of the established Leibovich prognosis score. RESULTS: Small platelet volume was associated with large tumors (p = 0.043), high Fuhrman grade (p = 0.001), sarcomatoid components (p <0.0001), histological tumor necrosis (p = 0.044) and vascular invasion (p = 0.022). On univariable and multivariable analyses small platelet volume accurately predicted recurrent renal cell carcinoma (continuously and binary coded) and cancer specific survival. Adding mean platelet volume to the Leibovich prognosis score improved its discriminative performance (c-index = 0.83, p = 0.004). CONCLUSIONS: Mean platelet volume represented a highly significant predictor of recurrence and cancer specific death in patients with renal cell carcinoma. This parameter improved the accuracy of the Leibovich prognosis score to better predict long-term outcomes in localized renal cell carcinoma cases after curative surgical resection.

MicroRNAs Associated with Von Hippel-Lindau Pathway in Renal Cell Carcinoma: A Comprehensive Review.

Renal cell carcinoma (RCC) are the most common renal neoplasia and can be divided into three main histologic subtypes, among which clear cell RCC is by far the most common form of kidney cancer. Despite substantial advances over the last decade in the understanding of RCC biology, surgical treatments, and targeted and immuno-therapies in the metastatic setting, the prognosis for advanced RCC patients remains poor. One of the major problems with RCC treatment strategies is inherent or acquired resistance towards therapeutic agents over time. The discovery of microRNAs (miRNAs), a class of small, non-coding, single-stranded RNAs that play a crucial role in post-transcriptional regulation, has added new dimensions to the development of novel diagnostic and treatment tools. Because of an association between Von Hippel-Lindau (VHL) genes with chromosomal loss in 3p25-26 and clear cell RCC, miRNAs have attracted considerable scientific interest over the last years. The loss of VHL function leads to constitutional activation of the hypoxia inducible factor (HIF) pathway and to consequent expression of numerous angiogenic and carcinogenic factors. Since miRNAs represent key players of carcinogenesis, tumor cell invasion, angiogenesis, as well as in development of metastases in RCC, they might serve as potential therapeutic targets. Several miRNAs are already known to be dysregulated in RCC and have been linked to biological processes involved in tumor angiogenesis and response to anti-cancer therapies. This review summarizes the role of different miRNAs in RCC angiogenesis and their association with the VHL gene, highlighting their potential role as novel drug targets.

Sampling of the anterior apical region results in increased cancer detection and upgrading in transrectal repeat saturation biopsy of the prostate.

OBJECTIVE: To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score. PATIENTS AND METHODS: The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone. RESULTS: The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown. CONCLUSION: Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy.

Current Insights into Long Non-Coding RNAs in Renal Cell Carcinoma.

Renal cell carcinoma (RCC) represents a deadly disease with rising mortality despite intensive therapeutic efforts. It comprises several subtypes in terms of distinct histopathological features and different clinical presentations. Long non-coding RNAs (lncRNAs) are non-protein-coding transcripts in the genome which vary in expression levels and length and perform diverse functions. They are involved in the inititation, evolution and progression of primary cancer, as well as in the development and spread of metastases. Recently, several lncRNAs were described in RCC. This review emphasises the rising importance of lncRNAs in RCC. Moreover, it provides an outlook on their therapeutic potential in the future.

Is There a Role for Active Surveillance in Low-Risk Prostate Cancer?

BACKGROUND: Active surveillance (AS) represents an expectant treatment strategy for clinically localized prostate cancer (PCa) with low-risk features. OBJECTIVE: The actual management as well as the pros and cons of AS were evaluated. METHODS: A systematic review of the recent literature was performed using the Medline databases. CONCLUSIONS: Since a substantial number of men die with rather than from PCa, there is a considerable role for AS in carefully selected men. AS may also represent a strategy to reduce the burden of overtreatment rooted in intensified PSA testing. Facing the imprecision of risk stratification based on transrectal ultrasound-guided biopsy, accurate clinical staging represents a major medical challenge. Counseling and care require empathy as well as a profound understanding of the biology and the natural history of PCa.

Utilization of bilateral infragluteal flaps for correction of overaggressive gluteal liposuction.

Liposuction continues to be one of the most frequently performed aesthetic surgical procedures. Typically, good results can be achieved. However, this procedure is not without any associated risks, such as infection, embolism, or contour deformities. These deformities are a feared sequelae and can result from faulty technique and will lead to decreased patient satisfaction. Methods for correction are limited but include repeat liposuction, lipofilling, or lifting procedures. We report a case of bilateral massive contour deformity after liposuction that we corrected with a novel technique using pedicled infragluteal flaps combined with a gluteal lifting procedure. The corrective operation resulted in a definitive improvement of the gluteal contour with great patient satisfaction.

Second TURB, restaging TURB or repeat TURB in primary T1 non-muscle invasive bladder cancer: impact on prognosis?

PURPOSE: A re-transurethral resection of the bladder (re-TURB) is a well-established approach in managing non-muscle invasive bladder cancer (NMIBC) for various reasons: repeat-TURB is recommended for a macroscopically incomplete initial resection, restaging-TURB is required if the first resection was macroscopically complete but contained no detrusor muscle (DM) and second-TURB is advised for all completely resected T1-tumors with DM in the resection specimen. This study assessed the long-term outcomes after repeat-, second-, and restaging-TURB in T1-NMIBC patients. METHODS: Individual patient data with tumor characteristics of 1660 primary T1-patients (muscle-invasion at re-TURB omitted) diagnosed from 1990 to 2018 in 17 hospitals were analyzed. Time to recurrence, progression, death due to bladder cancer (BC), and all causes (OS) were visualized with cumulative incidence functions and analyzed by log-rank tests and multivariable Cox-regression models stratified by institution. RESULTS: Median follow-up was 45.3 (IQR 22.7-81.1) months. There were no differences in time to recurrence, progression, or OS between patients undergoing restaging (135 patients), second (644 patients), or repeat-TURB (84 patients), nor between patients who did or who did not undergo second or restaging-TURB. However, patients who underwent repeat-TURB had a shorter time to BC death compared to those who had second- or restaging-TURB (multivariable HR 3.58, P = 0.004). CONCLUSION: Prognosis did not significantly differ between patients who underwent restaging- or second-TURB. However, a worse prognosis in terms of death due to bladder cancer was found in patients who underwent repeat-TURB compared to second-TURB and restaging-TURB, highlighting the importance of separately evaluating different indications for re-TURB.

Prognosis of Primary Papillary Ta Grade 3 Bladder Cancer in the Non-muscle-invasive Spectrum.

BACKGROUND: Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC) is a relatively rare diagnosis with an ambiguous character owing to the presence of an aggressive G3 component together with the lower malignant potential of the Ta component. The European Association of Urology (EAU) NMIBC guidelines recently changed the risk stratification for Ta G3 from high risk to intermediate, high, or very high risk. However, prognostic studies on Ta G3 carcinomas are limited and inconclusive. OBJECTIVE: To evaluate the prognostic value of categorizing Ta G3 compared to Ta G2 and T1 G3 carcinomas. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta-T1 bladder tumors from 17 hospitals were analyzed. Transurethral resection of the tumor was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and time to progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox-regression models with interaction terms stratified by institution. RESULTS AND LIMITATIONS: Ta G3 represented 7.5% (387/5170) of Ta-T1 carcinomas of which 42% were classified as intermediate risk. Time to recurrence did not differ between Ta G3 and Ta G2 (p = 0.9) or T1 G3 (p = 0.4). Progression at 5 yr occurred for 3.6% (95% confidence interval [CI] 2.7-4.8%) of Ta G2, 13% (95% CI 9.3-17%) of Ta G3, and 20% (95% CI 17-23%) of T1 G3 carcinomas. Time to progression for Ta G3 was shorter than for Ta G2 (p < 0.001) and longer than for T1 G3 (p = 0.002). Patients with Ta G3 NMIBC with concomitant carcinoma in situ (CIS) had worse prognosis and a similar time to progression as for patients with T1 G3 NMIBC with CIS (p = 0.5). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The prognosis of Ta G3 tumors in terms of progression appears to be in between that of Ta G2 and T1 G3. However, patients with Ta G3 NMIBC with concomitant CIS have worse prognosis that is comparable to that of T1 G3 with CIS. Our results support the recent EAU NMIBC guideline changes for more refined risk stratification of Ta G3 tumors because many of these patients have better prognosis than previously thought. PATIENT SUMMARY: We used data from 17 centers in Europe and Canada to assess the prognosis for patients with stage Ta grade 3 (G3) non-muscle-invasive bladder cancer (NMIBC). Time to cancer progression for Ta G3 cancer differed from both Ta G2 and T1 G3 tumors. Our results support the recent change in the European Association of Urology guidelines for more refined risk stratification of Ta G3 NMIBC because many patients with this tumor have better prognosis than previously thought.

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.

Benefit of Metastasectomy in Renal Cell Carcinoma: A Propensity Score Analysis.

INTRODUCTION: To quantify the magnitude of benefit of metastasectomy as compared to medical treatment alone in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: We therefore conducted a propensity score analysis of overall survival (OS) in 106 mRCC patients with metachronous metastasis, of whom 36 (34%) were treated with metastasectomy, and 70 (66%) with medical therapy alone. RESULTS: The most frequent metastasectomy procedures were lung resections (n = 13) and craniotomies (n = 6). Median time-to-progression after metastasectomy was 0.7 years (25th-75th percentile: 0.3-2.7). After a median follow-up of 6.2 years and 63 deaths, 5-year OS estimates were 41% and 22% in the metastasectomy and medical therapy group, respectively (log-rank P = .00007; Hazard ratio (HR) = 0.38, 95%CI: 0.21-0.68). Patients undergoing metastasectomy had a significantly higher prevalence of favorable prognostic factors, such as fewer bilateral lung metastases and longer disease-free intervals between nephrectomy and metastasis diagnosis. After propensity score weighting for these differences and adjusting for immortal time bias, the favorable association between metastasectomy and OS became much weaker (HR = 0.62, 95%CI: 0.39-1.00, P = .050). Propensity-score-weighted 5-year OS estimates were 24% and 20% in the metastasectomy and medical therapy group, respectively (log-rank P = .001). In exploratory analyses, the benefit of metastasectomy was confined to patients who achieved complete resection of all known metastases. CONCLUSION: Within the limitations of an observational study, these findings support the concept of metastasectomy being associated with an OS benefit in mRCC patients. Metastasectomies not achieving complete resection of all known lesions are likely without OS benefit.

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.

T1G1 Bladder Cancer: Prognosis for this Rare Pathological Diagnosis Within the Non-muscle-invasive Bladder Cancer Spectrum.

BACKGROUND: The pathological existence and clinical consequence of stage T1 grade 1 (T1G1) bladder cancer are the subject of debate. Even though the diagnosis of T1G1 is controversial, several reports have consistently found a prevalence of 2-6% G1 in their T1 series. However, it remains unclear if T1G1 carcinomas have added value as a separate category to predict prognosis within the non-muscle-invasive bladder cancer (NMIBC) spectrum. OBJECTIVE: To evaluate the prognostic value of T1G1 carcinomas compared to TaG1 and T1G2 carcinomas within the NMIBC spectrum. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for 5170 primary Ta and T1 bladder tumors from 17 hospitals in Europe and Canada were analyzed. Transurethral resection (TUR) was performed between 1990 and 2018. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Time to recurrence and progression were analyzed using cumulative incidence functions, log-rank tests, and multivariable Cox regression models stratified by institution. RESULTS AND LIMITATIONS: T1G1 represented 1.9% (99/5170) of all carcinomas and 5.3% (99/1859) of T1 carcinomas. According to primary TUR dates, the proportion of T1G1 varied between 0.9% and 3.5% per year, with similar percentages in the early and later calendar years. We found no difference in time to recurrence between T1G1 and TaG1 (p = 0.91) or between T1G1 and T1G2 (p = 0.30). Time to progression significantly differed between TaG1 and T1G1 (p < 0.001) but not between T1G1 and T1G2 (p = 0.30). Multivariable analyses for recurrence and progression showed similar results. CONCLUSIONS: The relative prevalence of T1G1 diagnosis was low and remained constant over the past three decades. Time to recurrence of T1G1 NMIBC was comparable to that for other stage/grade NMIBC combinations. Time to progression of T1G1 NMIBC was comparable to that for T1G2 but not for TaG1, suggesting that treatment and surveillance of T1G1 carcinomas should be more like the approaches for T1G2 NMIBC in accordance with the intermediate and/or high risk categories of the European Association of Urology NMIBC guidelines. PATIENT SUMMARY: Although rare, stage T1 grade 1 (T1G1) bladder cancer is still diagnosed in daily clinical practice. Using individual patient data from 17 centers in Europe and Canada, we found that time to progression of T1G1 cancer was comparable to that for T1G2 but not TaG1 cancer. Therefore, our results suggest that primary T1G1 bladder cancers should be managed with more aggressive treatment and more frequent follow-up than for low-risk bladder cancer.

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.

Seasonal Variations in the Diagnosis of Testicular Germ Cell Tumors: A National Cancer Registry Study in Austria.

We conducted a retrospective National Cancer Registry study in Austria to assess a possible seasonal variation in the clinical diagnosis of testicular germ cell tumors (TGCT). In total, 3615 testicular cancer diagnoses were identified during an 11-year period from 2008 to 2018. Rate ratios for the monthly number of TGCT diagnoses, as well as of seasons and half-years, were assessed using a quasi-Poisson model. We identified, for the first time, a statistically significant seasonal trend (p < 0.001) in the frequency of monthly newly diagnosed cases of TGCT. In detail, clear seasonal variations with a reduction in the tumor incidence during the summer months (Apr-Sep) and an increase during the winter months (Oct-Mar) were observed (p < 0.001). Focusing on seasonality, the incidence during the months of Oct-Dec (p = 0.008) and Jan-Mar (p < 0.001) was significantly higher compared to the months of Jul-Sep, respectively. Regarding histopathological features, there is a predominating incidence in the winter months compared to summer months, mainly concerning pure seminomas (p < 0.001), but not the non-seminoma or mixed TGCT groups. In conclusion, the incidence of TGCT diagnoses in Austria has a strong seasonal pattern, with the highest rate during the winter months. These findings may be explained by a delay of self-referral during the summer months. However, the hypothetical influence of vitamin D3 in testicular carcinogenesis underlying seasonal changes in TGCT diagnosis should be the focus of further research.

European Association of Urology (EAU) Prognostic Factor Risk Groups for Non-muscle-invasive Bladder Cancer (NMIBC) Incorporating the WHO 2004/2016 and WHO 1973 Classification Systems for Grade: An Update from the EAU NMIBC Guidelines Panel.

BACKGROUND: The European Association of Urology (EAU) prognostic factor risk groups for non-muscle-invasive bladder cancer (NMIBC) are used to provide recommendations for patient treatment after transurethral resection of bladder tumor (TURBT). They do not, however, take into account the widely used World Health Organization (WHO) 2004/2016 grading classification and are based on patients treated in the 1980s. OBJECTIVE: To update EAU prognostic factor risk groups using the WHO 1973 and 2004/2016 grading classifications and identify patients with the lowest and highest probabilities of progression. DESIGN, SETTING, AND PARTICIPANTS: Individual patient data for primary NMIBC patients were collected from the institutions of the members of the EAU NMIBC guidelines panel. INTERVENTION: Patients underwent TURBT followed by intravesical instillations at the physician's discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable Cox proportional-hazards regression models were fitted to the primary endpoint, the time to progression to muscle-invasive disease or distant metastases. Patients were divided into four risk groups: low-, intermediate-, high-, and a new, very high-risk group. The probabilities of progression were estimated using Kaplan-Meier curves. RESULTS AND LIMITATIONS: A total of 3401 patients treated with TURBT ± intravesical chemotherapy were included. From the multivariable analyses, tumor stage, WHO 1973/2004-2016 grade, concomitant carcinoma in situ, number of tumors, tumor size, and age were used to form four risk groups for which the probability of progression at 5 yr varied from <1% to >40%. Limitations include the retrospective collection of data and the lack of central pathology review. CONCLUSIONS: This study provides updated EAU prognostic factor risk groups that can be used to inform patient treatment and follow-up. Incorporating the WHO 2004/2016 and 1973 grading classifications, a new, very high-risk group has been identified for which urologists should be prompt to assess and adapt their therapeutic strategy when necessary. PATIENT SUMMARY: The newly updated European Association of Urology prognostic factor risk groups for non-muscle-invasive bladder cancer provide an improved basis for recommending a patient's treatment and follow-up schedule.