pT1 Bladder Cancer Research Articles

Clinical Significance of Horizontal and Vertical Margin of En Bloc Resection for Nonmuscle Invasive Bladder Cancer.

The primary advantage of en bloc resection of bladder tumors is to provide better diagnostic accuracy. However, the clinical significance of horizontal and vertical margin has not been demonstrated. We evaluated the clinical importance of surgical margins in patients who underwent en bloc resection of bladder tumors. We retrospectively analyzed the records of 140 consecutive patients who underwent en bloc resection of bladder tumors for nonmuscle invasive bladder cancer. We analyzed perioperative and oncological outcome, and compared patient demographics and recurrence-free survival for horizontal findings. The relationship between surgical margin and second transurethral resection outcome in pT1 bladder cancer was also analyzed. Mean tumor diameter was 17.2±9.8 mm. Pathological stages were 93 cases in pTa and 47 cases in pT1. Diagnostic rates for the horizontal and vertical margins were 63% and 99%, respectively. The rates of sessile, carcinoma in situ, high grade, and pT1 tumors were significantly higher in the horizontal margin positive group (41) than in the negative group (47). There was no significant difference in 2-year recurrence-free survival based on horizontal margin findings (negative: 72.4%, positive: 75.4%, p=0.87). A second transurethral resection was performed in 31 of the 47 pT1 patients; pT1 residue was seen only in vertical margin positive cases, and 5 pTa/pTis residues at the transurethral resection scar were seen in 15 horizontal margin positive patients. Horizontal margin positive findings were not associated with recurrence-free survival, but careful assessment is warranted regarding residue at the original site. A second transurethral resection should be considered in patients with horizontal and vertical margin positive pT1 bladder cancer.

Feasibility and accuracy of pathological diagnosis in en-bloc transurethral resection specimens versus conventional transurethral resection specimens of bladder tumour: evaluation with pT1 substaging by 10 pathologists.

En-bloc transurethral resection (TUR) of bladder tumour (ERBT) is designed to provide more accurate pathological diagnosis of specimens than conventional TUR of bladder tumour (cTURBT). Some studies have reported that T1 bladder cancer substage could be a prognostic factor in assessing tumour progression, but such substaging has not been widely adopted because of problems with pathological diagnosis using cTURBT specimens. The aim of this study was to evaluate the possible advantages of en-bloc TUR specimens in T1 substaging following assessment by a panel of 10 pathologists. We assessed the substages in 123 patients (cTURBT, n=91; ERBT, n=32) who were diagnosed with pT1 bladder cancer. We randomly selected 10 ERBT specimens and 10 cTURBT specimens with cancer invasion areas equivalent to those of their corresponding ERBT specimens. Ten pathologists performed pT1 substaging for pT1a/b/c and pT1m/e in 20 patients (cTURBT, n=10; ERBT, n=10). We evaluated diagnostic times and rates of diagnostic concordance among these pathologists, comparing cTURBT and ERBT. The median diagnostic times per slide were 87.7s [interquartile range (IQR) 71.9-109.2s) for cTURBT and 54.7s (IQR 46.0-59.6s) for ERBT (P=0.009). The rate of diagnostic concordance was significantly better for ERBT specimens. For pT1a/b/c, the median concordance rates were 50% for cTURBT and 80% for ERBT (P=0.02); for pT1m/e, the median concordance rates were 70% for cTURBT and 90% for ERBT (P=0.05). For pT1a/b/c, the average κ-values between the pathologist and the standard diagnosis were 0.04 for cTURBT and 0.47 for ERBT. The use of ERBT specimens shortened the diagnostic time and minimised interobserver variability for T1 substaging compared with the use of cTURBT specimens.

Vertical Lamina Propria Invasion Diagnosed by En Bloc Transurethral Resection is a Significant Predictor of Progression for pT1 Bladder Cancer.

T1 bladder cancer is characterized by high recurrence and aggressive progression. Muscularis mucosae invasion may be a prognostic factor for progression, but the limitations of conventional transurethral resection of bladder tumors make diagnosis difficult. We correlated degree of invasion with oncologic outcome and evaluated the utility of pathological diagnosis following en bloc resection of bladder tumors. We retrospectively analyzed the records of 123 consecutive patients diagnosed with pT1 bladder cancer between November 2013 and December 2018. Transurethral resection was conducted in 91 patients, and en bloc resection in 32 patients. All specimens were analyzed for invasion depth and pT1 substaging (T1a/b: invasion above or into/beyond muscularis mucosae, pT1m/e: microinvasive or extensively invasive). Primary end points were prognostic values of pT1 substaging and invasion depth. The secondary end point was the pathological diagnostic utility of en bloc resection. Median followup was 23 months. Three-year progression-free survival rate differed significantly depending on muscularis mucosae invasion (pT1a: 97.3%, pT1b: 72.8%; p=0.003) and invasion depth from basal membrane (<2 mm: 90.6%, ≥2 mm: 77.9%; p=0.03). Multivariate analysis showed that sessile tumor and invasion depth from basal membrane ≥2 mm were independent prognostic factors for progression. Diagnostic rates for pT1a/b and invasion depth were 77.6% and 85.9%, respectively, with transurethral resection, but 100% and 100% with en bloc resection (p=0.01 and p=0.03). Vertical lamina propria invasion is predictive of progression in T1 bladder cancer, underlining the importance of accurately diagnosing the degree of vertical lamina propria invasion with en bloc resection.

Outcomes of palliative cystectomy in patients with locally advanced pT4 bladder cancer

BackgroundRadical cystectomy (Cx) is the standard of care for muscle-invasive bladder cancer (BCa). In locally advanced pT4 BCa the oncologic outcome is inexplicit but Cx may be necessary for palliation. ObjectivesThe aim of this retrospective study was to evaluate the outcomes of Cx performed in patients with locally advanced pT4 BCa and to identify patient subgroups with improved outcome. MethodsBetween 2008 and 2017, we identified 76 of 905 patients who underwent Cx for pT4 BCa at a single tertiary referral center. The physical patients’ status was estimated according to the American Society of Anesthesiologists (ASA) classification. For the classification of postoperative complication rates, the Clavien-Dindo grading was used. Time-to-event variables with log-rank statistics were calculated with the use of the Kaplan-Meier method. ResultsMedian age was 74 years (range 42–90). Preoperatively, the physical status was estimated poor in 40 (52%) patients (ASA-score of ≥3). Overall, 19 (25%) patients had pT4b BCa, 41 (54%) patients were lymph node positive (c/pN+) and 14 (18%) patients had distant metastases (c/pM+). Within 30 and 90 days after surgery, 21% and 30% of the patients, respectively, developed severe complications (Clavien-Dindo grade ≥3). Overall, 30- and 90-day mortality rates were 9% and 11%, respectively. Moreover, 86% and 75% of patients who died within 30 and 90 days after surgery, respectively, had an ASA-score ≥3. At a median postoperative follow-up of 8 months (range 0–85), 53 (70%) patients have died. During the follow-up period, 46% of the patients died due to progressive disease, 16% died of a noncancer-specific cause, and for 8% of the patients, the reason remains unknown. Median overall survival (OS) and cancer-specific survival were 13.0 and 16.0 months, respectively. In subgroup analyses ASA-score ≥3 and hemoglobin <11.7 g/dl was significantly associated with poor OS. No statistically significant differences were detected between subgroups. ConclusionCx performed in patients with locally advanced pT4 BCa is associated with an increased mortality rate within 90 days postoperatively. Our study revealed that the ASA-score is a relevant and easily available tool to rate the patient´s condition and estimate postoperative outcome.

Prognosis of patients with T1 bladder cancer after en bloc transurethral resection of bladder tumor stratified by invasion to the level of the muscularis mucosa.

To evaluate the prognosis of patients with pT1 bladder cancer who underwent en bloc resection of bladder tumors (ERBTs), stratified by invasion to the muscularis mucosa (MM) level. Among 64 specimens obtained by ERBT with bipolar energy from patients with pT1 bladder cancer, MM was detected in 61 specimens. Thus, 61 specimens were included in this retrospective study. Patients were stratified by invasion to the MM level (pT1a, invasion above the MM level; pT1b, invasion within the MM level; and pT1c, invasion beyond the MM level). In specimens with discontinuous MM, invasion to the MM level was predicted from the dispersed MM in the specimen. The primary endpoints were progression-free survival (PFS) and cancer-specific survival (CSS). Progression occurred in 2/39 patients with pT1a (5.1%), 1/6 patients with pT1b (16.7%), and 6/16 patients with pT1c cancer (37.5%). Cancer death occurred in 1/39 patients with pT1a (2.6%), 0/7 patients with pT1b, and 3/16 patients with pT1c cancer (18.8%). Patients with pT1a or pT1b cancer had a significantly better prognosis than those with pT1c cancer. On univariate analysis, tumor size ≥ 3cm and pT1c were significantly associated with shorter PFS. On multivariate analysis, only pT1c was independently associated with shorter PFS. This is the first study evaluating the prognosis by T1 substaging based on invasion to the MM level using ERBT specimens. ERBT provided high-quality specimens for diagnosing the MM and showed poor prognosis in pT1c bladder cancer. ERBT could be an appropriate surgical approach for an accurate diagnosis and prognosis of the T1 bladder cancer substage.

High Stroma T-Cell Infiltration is Associated with Better Survival in Stage pT1 Bladder Cancer.

Stage pT1 bladder cancer (BC) shows highly diverse outcomes. Predictive markers are required to stratify patients for personalized treatment. The present study aimed to validate immune response quantification as a prognostic marker. Patients with pT1 BC (n = 167) treated by transurethral resection of the bladder (TURB) were enrolled. Formaldehyde-fixed paraffin-embedded material was stained for CD3 and CD8. Corresponding T cells were counted in three regions with the highest immune response. Numbers of tertiary lymphoid structures (TLS) and lymphocyte aggregates (LA) were quantified. High CD3+ stroma T-cell infiltration was associated with improved survival (p = 0.045), especially in the G3 subgroup (p = 0.01). Cluster with higher immune response showed less recurrence (p = 0.034) and favorable overall survival (OS) (p = 0.019). In contrast, higher CD3+ and CD8+ tumor T-cell infiltration seemed to have a negative impact on prognosis. TLS and LA were more frequently observed in G3 tumors, indicating an increased anti-tumoral immune response. We proved the role of immune cell infiltration and showed that higher infiltration numbers of CD3+ (not CD8+) lymphocytes in the stroma are associated with favorable outcome. Immune cell quantification could be used as a marker to help stratify patients’ risk and therefore, to optimize patients’ management and follow-up examination as well as possible therapies.

Prognostic and clinicopathologic value of ki-67 and profilin 1 immunohistochemical expression in primary pT1 urothelial bladder cancer.

To investigate the prognostic and clinicopathologic value of Ki-67 and profilin 1 immunohistochemical expression in primary pT1 papillary urothelial bladder cancer. This study included 88 male and 13 female pT1 primary bladder cancer patients. Demographic characteristics, tumor histological grade, tumor number, presence of concomitant carcinoma in situ, tumor size, and status of recurrence or progression were recorded for each patient. Expression of Ki-67 and profilin 1 was evaluated by immunohistochemical analysis of paraffin-embedded tumor tissues. The Pearson's Chi-square test was used for the analysis of qualitative data, and the Kaplan-Meier method and the log-rank test were used for the survival analysis. In the mean follow-up period of 52 months, 52 (51.5%) patients experienced recurrence, 24 (23.8%) patients experienced progression, and 17 (16.8%) patients died from bladder cancer-related causes. Ki-67 expression was significantly associated with tumor histological grade (P = 0.001). In multivariate analysis, Ki-67 positivity had significantly worse outcome for recurrence (P = 0.006) and mortality (P = 0.022). Ki-67-positive (Ki-67 index ≥15%) patients had shorter recurrence-free (P = 0.003), progression-free (P = 0.002), and cancer-specific (P = 0.003) survival. However, no statistically significant relationship was found between profilin 1 expression and clinicopathologic features and prognosis. Ki-67 is a highly predictive biomarker for recurrence-free, progression-free, and cancer-specific survival in pT1 bladder cancer patients, in whom prediction of recurrence and progression are difficult. Ki-67 expression can be safely combined with other prognostic factors. However, in pT1 bladder cancer patients, no significant relationship was found between profilin 1 expression and tumor characteristics or prognostic parameters.

Preoperative Clinical Predictors of Lymphovascular Invasion of Bladder Tumors at Transurethral Resection Pathology

Background: The assessment of lymphovascular invasion (LVI) on the specimens of a transurethral resection of bladder tumors (TURBT) is very important for risk stratification and decision-making on further treatment for bladder cancer. Objectives: The present study aimed to identify clinical predictors associated with the risk of bladder cancer with LVI before a first TURBT. Methods: A total of 291 patients underwent a first TURBT for bladder cancer at Toho University Sakura Medical Center between January 2012 and December 2016. We analyzed predictors of LVI based on data from 217 patients and predictors of high grade and ≥ pT1 tumors based on data from the medical records of 237 patients for comparison with LVI risk factors. Results: Univariate analysis significantly associated LVI with episodes of gross hematuria, positive urinary cytology, and larger, non-papillary and sessile tumors. Multivariate analysis selected larger tumors [odds ratio (OR) 1.39; 95 % confidence interval (CI) 1.08-1.78; p = 0.01], and non-papillary (OR 10.05; 95% CI 3.75-26.91; p < 0.01) and sessile (OR 2.65; 95% CI 1.18-5.93; p = 0.02) tumors as significant predictors of LVI. Some predictors such as tumor size and non-papillary tumors overlapped between high-grade and ≥ pT1 bladder cancer. Conclusions: These predictors can help clinicians to identify patients with, or who are at high-risk for LVI before undergoing a first TURBT and to determine priorities for preoperative evaluation and scheduling consecutive treatments.

Can preoperative imaging characteristics predict pT3 bladder cancer following cystectomy?

Imaging characteristics in bladder cancer (BC), such as hydronephrosis, are predictive of ≥ pT3 disease at time of radical cystectomy (RC). The predictive capacity of other findings, such as perivesical stranding (PS), remains unclear. We investigated whether PS was associated with ≥ pT3 BC in patients who did not receive neoadjuvant chemotherapy (NAC). We identified 433 patients with BC who underwent RC from 2003 to 2018 of which 128 did not receive NAC. Evidence of PS on pre-TURBT imaging was determined by radiologist review and a stranding grading system was created. Factors associated with PS and hydronephrosis were identified. Multivariable logistic regressions evaluated PS and hydronephrosis as predictors for ≥ pT3 BC. Of the 128 patients who did not receive NAC, 48 (38%) had pT3 and 12 (9%) had pT4 BC. 125 (98%) patients had CT and three (2%) had MRI. PS and hydronephrosis on imaging were identified in 19 (15%) and 45 (35%) patients. PS was not associated with imaging type (p = 0.38), BMI (p = 0.18), or pathologic T stage (p = 0.24). Hydronephrosis was more frequently associated with higher pathologic T stage (p = 0.034). Multivariable analysis demonstrated that PS was not predictive of ≥ pT3 BC (p = 0.457), while hydronephrosis was positively associated (p = 0.003). Stratification by grade of stranding did not improve the predictive capacity of PS (p = 0.667). While hydronephrosis is an indicator of higher stage BC, PS failed to be a reliable predictor of ≥ pT3 stage. These observations should give pause in using PS on imaging to guide decisions until further investigations can be explored.

PT1 high-grade bladder cancer: histologic criteria, pitfalls in the assessment of invasion, and substaging.

Most patients with bladder carcinoma are diagnosed with non-muscle-invasive disease, stage Ta, and pT1. Stage remains as the single most important prognostic indicator in urothelial carcinoma. Among the pT1 bladder cancer patients, recurrence and progression of disease occur in 50% and 10%, respectively. The identification of high-risk patients within the pT1 subgroup remains an important clinical goal and an active field of research. Substaging of pT1 disease has been claimed as important histologic discriminator by the 2016 World Health Organization (WHO) classification of the genitourinary tract tumors and by the 8th edition of the American Joint Committee on Cancer (AJCC) staging manual supporting its implementation in clinical practice. Interobserver variation in pT1 diagnosis and the associated pitfalls in pT1 assessment are the critical pathological issues. The aim of this review paper is to provide the practicing pathologist with the state of the art of morphological and immunohistochemical features useful for the diagnosis of early invasive bladder carcinomas, including practical clues on how to avoid relevant interpretative pitfalls, and to summarize the current status of pT1 substaging.

MP73-12 VERTICAL INVASION IS IMPORTANT PREDICTOR FOR PT1 BLADDER CANCER PROGRESSION-EFFICACY OF EN-BLOC TUR SPECIMEN-

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP73)1 Apr 2020MP73-12 VERTICAL INVASION IS IMPORTANT PREDICTOR FOR PT1 BLADDER CANCER PROGRESSION-EFFICACY OF EN-BLOC TUR SPECIMEN- Takafumi Yanagisawa*, Jun Miki, Takashi Yorozu, Hirotaka Suzuki, Takayuki Sano, Takashi Otsuka, Keiichiro Miyajima, Masatoshi Tanaka, Taishi Matsuura, Keigo Sakanaka, Koki Obayashi, Takahiro Kimura, Hiroyuki Takahashi, Shin Egawa, and Tokyo Japan Takafumi Yanagisawa*Takafumi Yanagisawa* More articles by this author , Jun MikiJun Miki More articles by this author , Takashi YorozuTakashi Yorozu More articles by this author , Hirotaka SuzukiHirotaka Suzuki More articles by this author , Takayuki SanoTakayuki Sano More articles by this author , Takashi OtsukaTakashi Otsuka More articles by this author , Keiichiro MiyajimaKeiichiro Miyajima More articles by this author , Masatoshi TanakaMasatoshi Tanaka More articles by this author , Taishi MatsuuraTaishi Matsuura More articles by this author , Keigo SakanakaKeigo Sakanaka More articles by this author , Koki ObayashiKoki Obayashi More articles by this author , Takahiro KimuraTakahiro Kimura More articles by this author , Hiroyuki TakahashiHiroyuki Takahashi More articles by this author , Shin EgawaShin Egawa More articles by this author , and Tokyo JapanTokyo Japan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000959.012AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: T1 bladder cancer has various pathological features individually and has high rate of not only recurrence but progression. Some studies have reported invasion depth and invasion to muscularis mucosae (MM) are prognostic factor of progression, but it is still controversial. We analyzed correlation between degree of invasion and oncological outcome and also evaluated the utility of pathological diagnosis with En-bloc TUR specimen. METHODS: We retrospectively analyzed the record of the 123 patients who were diagnosed as pT1 bladder cancer in our institution between November 2011 and December 2018. Conventional TURBT (n=91) and En-bloc TUR (n=32) were eligible. All specimens were reviewed by single urological pathologist and diagnosed invasion depth, number, maximum diameter and presence of MM invasion. We analyzed recurrence free survival (RFS) and progression free survival (PFS) with Kaplan-Meyer method and evaluated predictor of recurrence and progression with Cox proportional hazard model. RESULTS: Median follow up period was 23 months. The overall 3-year RFS was 65.4%, and the 3-year PFS was 86.1%. The 3-year PFS had significant difference in presence of MM invasion (pT1a: 97.3%, pT1b: 72.8%), invasion depth from basal membrane (<2mm: 90.6%, ≧2mm: 77.9%, p=0.03), maximum invasion diameter (<5mm: 93.4%, ≧5mm: 70.7%, p=0.03). In multivariate analysis, history of TURBT, sessile, MM invasion were independent prognostic factor of progression. The diagnostic rate of MM invasion and invasion depth were 77.6%, 85.9% in TURBT specimen, however that of En-bloc TUR were both 100% (p=0.01, 0.03). CONCLUSIONS: Vertical invasion is strongly associated with progression of T1 bladder cancer. It is important to diagnose the degree of vertical invasion correctly with En-bloc TUR specimen. Further study with more number of cases and long term follow up is needed. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1126-e1126 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takafumi Yanagisawa* More articles by this author Jun Miki More articles by this author Takashi Yorozu More articles by this author Hirotaka Suzuki More articles by this author Takayuki Sano More articles by this author Takashi Otsuka More articles by this author Keiichiro Miyajima More articles by this author Masatoshi Tanaka More articles by this author Taishi Matsuura More articles by this author Keigo Sakanaka More articles by this author Koki Obayashi More articles by this author Takahiro Kimura More articles by this author Hiroyuki Takahashi More articles by this author Shin Egawa More articles by this author Tokyo Japan More articles by this author Expand All Advertisement PDF downloadLoading ...

Expression of E-cadherin, Ki-67, and p53 in urinary bladder cancer in relation to progression, survival, and recurrence.

Although the incidence varies with age and gender, urothelial bladder cancer is a relatively frequently occurring malignancy with variable clinical behavior that often has high recurrence rates. In this study, we analyzed the tumor tissues of 224 patients with pTa, pT1, and pT2 urinary bladder cancer. We performed a histomorphologic analysis and immunohistochemistry for p53, Ki-67, and E-cadherin, which were selected as markers of the malignant process. For pTa and pT1, univariate analyses of cancer-specific survival (CSS), progression-free survival (PFS), and recurrence-free survival (RFS) were calculated using the Kaplan-Meier method, the logrank test and Cox regression. Multivariate analysis was performed by the Cox regression analysis. Ki-67 (P<0.001) was significantly associated with CSS, but the highest association was shown for E-cadherin (P<0.001). For pT1 and pTa, the Kaplan-Meier analysis and the log-rank test revealed significantly worse PFS for patients with higher levels of Ki-67 (P<0.001) and lower levels of E-cadherin (P<0.001). Based on these obtained results, it can be clearly stated that Ki-67 and E-cadherin expression levels are associated with CSS, PFS and RFS. The clinical utility of these markers is valuable for pTa and pT1 urinary bladder cancer and should be further verified with prospective multi-center trials.

Laparoscopic versus open radical cystectomy in the treatment of locally advanced T3 and T4 bladder cancer: Perioperative and Mid-term oncological outcomes.

In this study, we aim to compare the perioperative and midterm oncological outcomes in patients with advanced bladder cancer and those who had laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC). We retrospectively reviewed medical records of patients who underwent LRC or ORC in a single center between 2008 and 2014 with a pathological diagnosis of pT3 and pT4 bladder cancer. Thirty-five and 39 patients were included in the study as part of the LRC and ORC groups, respectively. There was no statistically significant difference between the two groups in terms of disease-free survival (LRC, 39.8±4.86 months; ORC, 45.47±8.92 months, P=0.896). Average estimated blood loss and length of hospitalization were significantly less in the LRC group. The overall survival rates of patients at 1, 2, and 3 years were 73%, 46%, and 46% in the ORC group and 78%, 65%, and 40% in the LRC group, respectively, and there was no statistically significant difference between the two groups. One patient in the ORC group experienced rectal injury in the form of a serosal tear, which was repaired primarily without any postoperative sequelae. There were no conversions in the laparoscopic group. Similarly, in 1 patient, rectal serosal tear was repaired preoperatively. Our study showed that LRC provides midterm oncological outcomes similar to ORC in the treatment of locally advanced T3 and T4 bladder cancer. However, long-term oncological and functional outcomes are required.

Prognostic value of T1 substaging on oncological outcomes in patients with non-muscle-invasive bladder urothelial carcinoma: a systematic literature review and meta-analysis

PurposeTo evaluate the prognostic value of substaging on oncological outcomes in patients with T (or pT1) urothelial carcinoma of the bladder.MethodsA literature search using PubMed, Scopus, Web of Science, and Cochrane Library was conducted on March 2019 to identify relevant studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The pooled disease recurrence (DR) and disease progression (DP) rate in T1(or pT1) patients were calculated using a fixed or random effects model.ResultsOverall 36 studies published between 1994 and 2018 including a total of 6781 bladder cancer patients with T1(or pT1) stage were selected for the systematic review and meta-analysis. Twenty-nine studies reported significant association between tumor infiltration depth or muscularis mucosa (MM) invasion and oncological outcomes. Totally 12 studies were included in the meta-analysis. MM invasion (T1a/b/c [or pT1a/b/c] or T1a/b [or pT1a/b] substaging system) was associated with DR (pooled HR: 1.23, 95%CI: 1.01–1.49) and DP (pooled HR: 2.61, 95%CI: 1.61–4.23). Tumor infiltration depth (T1 m/e [or pT1 m/e] substaging system) was also associated with DR (pooled HR: 1.49, 95%CI: 1.11–2.00) and DP (pooled HR: 3.29, 95%CI: 2.39–4.51).ConclusionsT1(or pT1) substaging in patients with bladder cancer is of prognostic value as it is associated with oncologic outcomes. Inclusion of this factors into the clinical decision-making process of this heterogeneous tumor may improve outcomes, while avoiding over- and under-treatment for T1(or pT1) bladder cancer.

Usefulness of the inchworm sign on DWI for predicting pT1 bladder cancer progression.

To evaluate the significance of the presence or absence of an "inchworm sign" on DWI for the recurrence and progression of T1 bladder cancer. We retrospectively analyzed 91 patients with pT1 urothelial carcinoma who underwent DWI prior to transurethral resection between 2007 and 2016. DWI of the dominant tumors was scrutinized for inchworm signs at b = 1000s/mm2. The association of the presence of the inchworm sign with progression and recurrence was analyzed; progression was defined as recurrence to stage T2 or higher and/or N+, and/or M1. An inchworm sign was seen in 65 cases (71%), while it was absent in 26 cases. Among the 65, 25 (38%) had confirmed tumor recurrence, while in the remaining 26, 14 (54%) had confirmed recurrence (median time post TURB = 7.9 and 10.1months for each). At the time of recurrence, the tumor had progressed in one (2%) inchworm-sign-positive and seven (27%) inchworm-sign-negative cases. The progression rate of inchworm-sign-negative cases was significantly higher than that of inchworm-sign-positive cases (hazard ratio = 17.2, p = 0.0017), whereas there was no significant difference in the recurrence rate between two groups. The absence of an inchworm sign and histological grade 3 were independent risk factors for progression (p < 0.001 and 0.010, respectively). The absence of an inchworm sign on DWI was a significant prognostic factor for progression of T1 bladder cancer. Morphological evaluation of DWI signals may therefore be a useful adjunct to preoperative assessment of biological aggressiveness. • An inchworm sign is a simple diagnostic criterion that characterizes only the shape of the tumor signal on DWI, and potentially serves as an imaging biomarker to predict clinical aggressiveness. • The absence of an inchworm sign on DWI is a significant indicator of progression of T1 bladder cancer.

Is neoadjuvant chemotherapy for pT2 bladder cancer associated with a survival benefit in a population-based analysis?

BackgroundPatients with organ confined muscle-invasive bladder cancer (MIBC) who are candidates for radical cystectomy (RC) should receive neoadjuvant chemotherapy (CHT). However, the most contemporary CHT use rates indicate low adherence to these guidelines. We tested contemporary neoadjuvant CHT rates and associated cancer-specific mortality (CSM) and overall mortality (OM) in pT2N0 MIBC patients treated with RC. Materials and methodsWithin the SEER database (2004–2015), we identified patients with pT2N0 MIBC patients who underwent RC. CHT administration rates were evaluated using estimated annual percentage changes (EAPCs) analyses. After inverse probability of treatment weighting (IPTW), Kaplan–Meier (KM) analyses and Cox regression models (CRMs) were used to test the effect of CHT vs no CHT on survival. Landmark analyses tested for immortal time bias. ResultsOf 3978 RC patients, 38.2% of patients received CHT. Between 2004 and 2015, CHT rates increased from 15.9% to 66.2% (EAPC: +14.2%; p < 0.001). IPTW-adjusted KM showed 10-year CSM-free survival rates of 78.9% for CHT vs 76.7% for no CHT patients (p = 0.6). Similarly, IPTW-adjusted KM showed 10-year OM-free survival rates of 54.6% for CHT vs 57.9% for no CHT patients (p = 0.8). In IPTW-adjusted MCRMs, CHT was not significantly associated with lower CSM (HR 0.97, CI 0.82–1.14; p = 0.7) or OM (HR 1.02, CI 0.90–1.16; p = 0.7). Virtually the same CSM and OM rates were recorded after landmark analyses. ConclusionsCHT use in pT2N0 MIBC RC patients sharply increased over the study span. However, neoadjuvant CHT was not associated with better survival in this patient group.

40 - The importance of pathological stage and grade review of primary pT1 bladder cancers after second transurethral resection

40 - The importance of pathological stage and grade review of primary pT1 bladder cancers after second transurethral resection

Evaluating Guideline Adherence for T1 Bladder Cancer Treatment and Surveillance: A Retrospective German Multicenter Observation

Introduction: To mirror guideline-adherence for pT1 bladder cancer treatment in Northern Germany. Materials and Methods: Overall, 111 patients with pT1 diagnosis were treated at 4 institutions. Guideline-adherence was defined as repeat resection, instillation, and quarterly cystoscopy. Patient characteristics and pathological parameters were assessed. We summarized patients using descriptive analyses and evaluated guideline-adherence within selected subgroups. We created a multivariable model to identify predictors of guideline-adherence. Results: Median age was 75 years (range 39–94 years), multifocal tumors were found in 44.1%, early instillation was performed in 33.3%, and repeat resection was performed in 77.5%. Of 62.2% who underwent instillation, 59.4% received BCG, while 40.6% received Mitomycin C or other agents. Cystoscopic follow-up was performed in 81.8%. Guideline-adherence was met in 56.8%. Patients aged below the median met adherence metrics more often compared to those above the median (66.7 vs. 46.3%; p = 0.030). Men more frequently met adherence metrics compared to women (62.1 vs. 37.5%; p = 0.038). More patients with multifocal tumors met all 3 adherence metrics (69.4 vs. 48.0%; p = 0.050), as compared to those with unifocal lesions. In multivariable analyses, age-adjusted comorbidity (OR 0.75; 95% CI 0.59–0.94; p = 0.011) and multifocality (OR 2.62; 95% CI 1.09–6.27; p = 0.031) were predictors of guideline-adherence. Conclusions: We found non-adherence in more than one-third of patients and disparities among patients of different age and according to tumor focality. Larger samples and prospective studies are needed to delineate and eradicate treatment disadvantages in these high-risk patients.

Bladder cancer detection by urinary extracellular vesicle mRNA analysis.

ObjectiveUrinary extracellular vesicles (EV) could be promising biomarkers for urological diseases. In this retrospective feasibility study, we conducted biomarker screening for early stage bladder cancer using EV mRNA analysis.MethodsBiomarker candidates were identified through RNA-seq analysis of urinary EV from patients with non-muscle invasive bladder cancer (N=3), advanced urothelial cancer (N=3), no residual tumor after TURBT (N=2), and healthy and disease controls (N=4). Diagnostic performance was evaluated by RT-qPCR in a larger patient group including bladder cancer (N=173), renal pelvis and ureter cancer (N=33), no residual tumor and non-cancer disease control (N=36).ResultsUrinary EV SLC2A1, GPRC5A and KRT17 were overexpressed in pT1 and higher stage bladder cancer by 20.6-fold, 18.2-fold and 29.5-fold, respectively. These genes allowed detection of non-muscle invasive bladder cancer (AUC: 0.56 to 0.64 for pTa, 0.62 to 0.80 for pTis, and 0.82 to 0.86 for pT1) as well as pT2 and higher muscle invasive bladder cancer (AUC: 0.72 to 0.90). Subgroup analysis indicated that these markers could be useful for the detection of cytology-negative/-suspicious and recurrent bladder cancers.ConclusionThree urinary EV mRNA were discovered to be elevated in bladder cancer. Urinary EV mRNA are promising biomarkers of urothelial cancer and worth further investigation.

Predicting the tumorigenic phenotype of human bladder cancer cells by combining with fetal rat mesenchyme

BackgroundIn nonmuscle invasive bladder cancer patients, prediction of pTa and pT1 bladder cancer recurrence and progression must be established. Micropapillary structures have been defined as small clusters of invasive cancer cells having features of the epithelial-mesenchymal transition. Since the stromal microenvironment helps to induce the epithelial-mesenchymal transition, interactions between cancer cells and stroma should be closely examined to predict the tumorigenic phenotype of human bladder cancer cells. Materials and methodsTo investigate differences in the responsiveness of cancer cells to stroma, we combined 3 established human bladder cancer cell lines (high-grade T24 and UM-UC-3 cells, and low-grade papillary RT4 cells) with fetal rat mesenchyme. ResultsAmong 3 bladder cancer cell lines, the expression profiles of p63 isoforms were distinct, i.e., p63γ in T24 cells, p63β in UM-UC-3 cells, and p63α in RT4 cells. Tumors formed by T24 cells combined with fetal mesenchyme formed micropapillary-like structures, whereas those formed by T24 cells alone did not. T24 cells combined with fetal mesenchyme showed poor differentiation, e.g., innumerable chromatic atypia in the nuclei, higher levels of chromatic condensation, and increased nucleoli. In contrast, both UM-UC-3 and RT4 cells combined with fetal mesenchyme did not form micropapillary-like structures. Ki-67 and p63 labeling indices were significantly elevated by combining fetal mesenchyme with T24 cells but not with the others. ConclusionsBy mixing cancer cells with fetal mesenchyme, our data demonstrated that formation of micropapillary-like structures may predict the tumorigenic phenotype of invasive bladder cancer cells. Taken together, distinct expression profiles of p63 isoforms may predict poor outcomes in invasive bladder cancer.