Muscle-invasive Urinary Bladder Cancer Research Articles

The emerging role of cell cycle protein p53 expression by tumor cells and M2-macrophage infiltration in urinary bladder cancer.

To investigate the association between p53 expression in tumor cells and intratumoral macrophage infiltration in muscle-invasive urinary bladder cancer (MIBC) in relation to clinical and pathological variables and outcomes after radical cystectomy. Tumor specimens of the primary tumor from patients treated with radical cystectomy for MIBC were immunostained with the M2-macrophage-specific marker CD163 and the cell cycle protein p53. The expression of these markers was analyzed in relation to patients´ and tumor characteristics and outcome. Out of 100 patients with urinary bladder cancer (UBC) pathological stage T1-4 N0-3 M0, 77% were men. The patients had a median age of 69 years and 80% had nonorgan-confined tumors (pT3-4). Lymph node metastasis was found in 42 (42%) of all patients. P53-positive expressions were found in 63 (63%) patients. Strong macrophage infiltration in the tumor microenvironment was shown in 74 (74%) patients. Combinations of CD163/p53 status were as follows: CD163+/p53+, 50%; CD163+/p53-, 24%; CD163-/p53+, 13%; and CD163-/p53-, 13%. Patients with CD163+/P53+ had higher proportions of organ-confined tumors. In the present series of patients with MIBC treated with cystectomy, we found that high CD163+ macrophage infiltration in the tumor micro-environment often was combined with p53+ cancer cells. This simultaneous expression of p53 by tumor cells and increased infiltration of M2-macrophages in the tumor microenvironment was associated with improved CSS, which might indicate a possible protective effect of M2 macrophages in p53+ tumors. Further investigations are needed to explore the biological relation between mutational burden and immune profile in MIBC.

Tumor-infiltrating lymphocytes predict survival in ≥ pT2 urothelial bladder cancer

Tumor-infiltrating lymphocytes (TILs) are associated with improved survival in several types of cancers, including genitourinary cancers. However, multiple different scoring methods used to assess TILs complicate the comparison of different studies and are not always suitable for daily practice. In 2014, the International TILs Working Group (ITWG) proposed a simple and robust assessment method for a more standardized evaluation of TILs. Here, we validated this system in muscle-invasive urinary bladder cancer (MIBC). Patient history and histologic specimens from 203 patients with MIBC were retrospectively analyzed. The stromal TIL (sTIL) score was determined using the ITWG system and 3 groups were defined according to the degree of stromal lymphocytic infiltration: low (0–10%), intermediate (10–55%) and high (55–100%). Associations between sTIL score, clinicopathological variables, tumor-specific survival (TSS), overall survival (OS), and disease-free survival (DFS) were analyzed. High stromal lymphocytic infiltration was associated with significantly higher OS, TSS and DFS when compared to low grade sTILs. The survival benefit remained statistically significant in multivariate analyses, confirming that sTILs are a strong independent positive prognostic factor in patients with MIBC. In summary, the degree of sTILs as defined by the ITWG robustly predicts survival in MIBC patients. Prospective studies with larger case numbers are needed to determine whether sTILs should be included in staging guidelines and how they could aid in therapeutic decision making.

Trimodale Therapie des muskelinvasiven Blasenkarzinoms – eine äquivalente Alternative zur Operation im lokalisierten Tumorstadium?

BackgroundThe standard treatment of muscle-invasive bladder cancer is cystectomy with pelvic lymphadenectomy. Primary organ-preserving trimodal treatment is considered an alternative to radical surgery.ObjectiveThe concept and results of trimodal treatment, consisting of initial transurethral resection of the bladder tumor (TURBT) followed by simultaneous chemoradiotherapy (CRT), are presented.Material and methodsAn evaluation of retrospective case series and prospective treatment optimization studies on organ-preservation concepts was carried out. Comparative meta-analyses comparing cystectomy with trimodal treatment are presented.ResultsA complete TURBT including bladder mapping and tumor ground biopsy should be done before CRT. Radiosensitization should be with cisplatin-based chemotherapy or with a combination of 5‑fluorouracil and mitomycin C. Complete response rates after TURBT plus CRT are achieved by 60–90% of patients and 5‑year survival rates of 40–75%, with preservation of the bladder in approximately 80% of surviving patients.ConclusionTrimodal treatment is a viable alternative to radical cystectomy with curative intention for patients with muscle-invasive urinary bladder cancer. Patients with early tumors (cT2/3N0) are particularly suitable in whom the initial TURBT leads to complete tumor resection (R0). Older patients can also benefit from this approach.

Intracorporeal Urinary Diversion versus Extracorporeal Urinary Diversion during Robot-Assisted Radical Cystectomy

Abstract Background/Aim: Radical cystectomy (RC) is a fundamental step in the therapeutic plan of nonmuscle and muscle-invasive urinary bladder cancer. Open RC is a surgical procedure with high morbidity and as such robot-assisted RC (RARC) has been established as an efficient alternative. Although in the beginning, the urinary diversion step during RARC was mostly performed extracorporeally nowadays a preference of the intracorporeal approach is yearly increasing. The aim of this review is to compare these two techniques of urinary diversion and depict the latest trends of current research on this field. Materials and Methods: A literature search of MEDLINE database (March 26, 2022) was performed to retrieve the articles published in English that are dated between January 1, 2010 and February 28, 2022. The search strategy included terms: “intracorporeal,” “vs,” “extracorporeal,” “urinary,” “diversion,” “comparison,” “after,” “RARC” and “or”. Results: Intracorporeal urinary diversion (ICUD) is strongly associated with lower perioperative blood loss and blood transfusion needs compared with the extracorporeal urinary diversion (ECUD). ICUD prolongs the operative duration. However, when ICUD is performed by experienced surgeons or in high volume centers, operative duration is comparable for ICUD and ECUD. The two approaches are assessed as equal in respect of postoperative complications. Conclusion: The debate as to whether ICUD must replace ECUD and become the standard of care does not end with this review. Intracorporeal approach in most of the studies seems to be associated with prolonged operative duration, lower transfusion needs, and equal complication rates when compared with ECUD. However, the contradiction of the results and the low quality of the available data demand the conduction of randomized prospective studies comparing ICUD and ECUD in order to offer the best available treatment to the patient.

EDITORIAL COMMENT

Radical cystectomy (RC) still represents the gold standard therapy for muscle-invasive urinary bladder cancer (MIBC) with 66% recurrence-free survival at 10 years follow-up.1 In the last decade robot-assisted radical cystectomy (RARC) has been increasingly adopted for the treatment of MIBC, resulting not inferior to open surgery regarding surgical complications and oncological outcomes, whereas the supposed benefits of a mini-invasive approach and less surgical trauma basing on reduced hospital stay and improved postoperative QoL could be not demonstrated.

High Grade Muscle-Invasive Urinary Bladder Cancer in A 36 Year Old Male Patient: A Case Report & Review of Literature

We are reporting a case of urothelial bladder cancer in a 36 year old male patient with no history or exposure to any risk factors. The incidence of urothelial bladder cancer is very low in young individuals i.e. below 40 years of age with reported rate of incidence around 0.1-0.4 %. Most of the times, these young individuals present with non-muscle invasive bladder cancer with low grade and low stage. As the age increases, the incidence of high grade bladder cancer increases along with it. The index case presented with high grade muscle invasive bladder cancer at the time of diagnosis without any known risk factors. The 5-year survival of urothelial bladder cancer is better in young patients (93.8 %) as compared to older people(85.1 %). Cigarette smoking is responsible for development of bladder cancer in majority of patients followed by exposure to occupational carcinogens. Role of genetic alterations in development of bladder cancer is still under research and process of urothelial bladder carcinogenesis is unanswered in young individuals.

A prospective multicenter study of visual response-evaluation by cystoscopy in patients undergoing neoadjuvant chemotherapy for muscle invasive urinary bladder cancer

Purpose To evaluate a method of transurethral visual response-staging in patients with urothelial muscle-invasive urinary bladder cancer (MIBC), undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Methods A prospective study at four Swedish cystectomy centers, cystoscopy was performed after final NAC-cycle for MIBC. Fifty-six participants underwent cystoscopy for visual staging of the tumor immediately pre-RC. Visual assessments were correlated to pathoanatomical outcomes post-RC. Results Seventeen tumors were classified as complete response (CR), i.e. pT0. Twenty-five patients had residual MIBC and 14 had non-muscle invasive residual tumors (NMIBC). Of the 39 patients with residual tumor, 25 were correctly identified visually (64%). Eleven patients were pN+. The diagnostic accuracy of cystoscopy to correctly identify complete response or remaining tumor was 70% (CI = 56–81%) with a sensitivity of 64% (CI = 47–79%), specificity 82% (CI = 57–96%), PPV 89% (CI = 74–96%) and NPV 50% (CI =38–61%). Twenty-eight cystoscopy evaluations showed signs of residual tumors and 3/28 (11%) were false positive. In 4/14 patients assessed having residual NMIBC the estimates were correct, 8/14 had histopathological MIBC and 2/14 had CR. In 11/14 patients (79%), the suggested visual assessment of MIBC was correct, 2/14 had NMIBC and 1/14 had CR. Twenty-eight cystoscopies had negative findings, 14 were false negatives (50%), when cystoscopy falsely predicted pT0. Among them there were eight patients with pTa, pT1 or pTis and six MIBC-tumors. In 17 patients with histopathological pT0, 14 were correctly identified with cystoscopy (82%). Conclusion Cystoscopy after the final NAC-cycle cannot robustly differentiate between NAC-responders and non-responders. Visually, negative MIBC-status cannot be determined safely.

Control computerized tomography in neoadjuvant chemotherapy for muscle invasive urinary bladder cancer has no value for treatment decisions and low correlation with nodal status

Background Control computerized tomography (cCT) is routinely used in many cystectomy centres before the final treatment cycle in patients with muscle-invasive urinary bladder cancer (MIBC) undergoing neoadjuvant chemotherapy (NAC). This is for evaluating response or nonresponse to NAC treatment. In a real-world retrospective cohort, we intended to evaluate the frequency of changed individual treatment strategies following cCT and to investigate any discrepancies between cCT-results on nodal staging and final pN-stages. Methods We performed a retrospective data-based, multicenter study of 242 MIBC-patients, staged cT2N0M0-cT4aN0M0, having undergone NAC and radical cystectomy (RC) between 2008 and 2019 at four Swedish cystectomy centres. Statistical analysis was performed using IBM SPSS statistics 26. Results Overall, 139/242 patients were examined with cCT. Six patients were staged as progressive at cCT and 5/139 (3.6%) underwent a change of previously planned treatment strategy. 2/6 patients with suspected progression (33%) did not change strategy and underwent all preplanned NAC-cycles plus RC. Only 1/6 patients assigned as progressive at the cCT, showed progression in the postoperative pathology specimen. In total 133/139 patients were considered being without progress on cCT, yet 28/133 (21%) presented with nodal progression at postoperative pathology examinations. Only 1/29 patients with histopathologically verified nodal dissemination were detected with cCT, thus 28/29 (96.6%) with pN + were undetected. The sensitivity for cCT to predict pTNM was 17% CI [0%–64%] and the specificity was 78% CI [71%–86%]. Conclusions CCT prior to the final treatment cycle of NAC in MIBC, leads to a low percentage of treatment strategy changes and cCT cannot accurately predict pN-status.

Thromboembolism in Muscle-Invasive Bladder Cancer. A Population-based Nationwide Study.

Routine VTE prophylaxis within 30 days of radical cystectomy (RC) for urinary bladder cancer (UBC) is used to protect from venous thromboembolism (VTE). However, randomized studies and nationwide population-based studies are lacking. To study VTE and risk factors for VTE in muscle-invasive UBC in a nationwide population-based series, with a focus on the association with RC with and without chemotherapy. We studied all patients with clinical stage T2-T4 UBC diagnosed 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe). Previous VTE events and risk factors for VTE were registered from 1987. Cox regression analyses and Kaplan-Meier curves were performed to study risk factors for VTE and cumulative incidence of VTE. In 9720 patients (71%males) with a median age of 74 years 546 (5.6%) had VTE after diagnosis. In Cox analyses controlling for patient's and tumour characteristics, and risk factors for VTE, VTE after diagnosis and first treatment date were associated with chemotherapy with or without RC. Cumulative incidence of VTE increased during 24 months after diagnosis and first treatment date. VTE were less common in patients with previous cardiovascular disease. VTE was commonly observed after 30 days from diagnosis and from first treatment date in patients with T2-T4 UBC, particularly after chemotherapy. The findings suggest that long-term intervention studies of benefit and possible harms of VTE prophylaxis after UBC should be undertaken.

PD-L1 Expression in Muscle-Invasive Urinary Bladder Urothelial Carcinoma According to Basal/Squamous-Like Phenotype.

Urothelial carcinoma (UC) is the most common histologic type of urinary bladder cancer, and muscle-invasive UC shows aggressive behaviors. Programmed cell death-1 (PD-1)/programmed cell death-ligand 1 (PD-L1) blockades have been approved as standard treatments for patients with advanced stage UC. A total of 166 muscle-invasive urinary bladder cancer (MIBC) patients, who underwent transurethral resection of the bladder or cystectomy from 2004 to 2010 were included. We evaluated PD-L1 expression by the SP142 and SP263 assays and classified the cases “positive” or “negative” according to the manufacturer’s recommendations. We performed immunohistochemistry (IHC) for cytokeratin (CK) 5/6, CK14, GATA3, FOXA1, and CK20 and classified samples as Basal-Squamous-like (BASQ) or non-BASQ subtype. The overall concordance rate for PD-L1 expression is 91.6% (152/166) (kappa = 0.732). The SP142 assay showed 15.1% positivity; the SP263 assay showed 23.5%. The high positivity in the SP142 and SP263 assay was significantly correlated with positive CK5/6, CK14 expression, negative GATA3, FOXA1, and CK20 expression. Classification according to IHC expression resulted in 12.0% (20/166) of samples being classified as BASQ subtype and 88.0% (146/166) of samples being classified as non-BASQ subtype. High positivity in the SP142 and SP263 assay was significantly correlated with the BASQ subtype (p < 0.001, both). Our study is the first to analyze the association of immunohistochemically defined BASQ and non-BASQ subtypes with two PD-L1 assays in MIBC. In conclusion, we revealed that a high PD-L1 positive rate in all PD-L1 assays was significantly associated with the BASQ-subtype, and these results suggest that the BASQ classification may be important to apply the PD-1/PD-L1 blockades in MIBC.

Chloride Intracellular Channel Protein 1 (CLIC1) Ιs Over-expressed in Muscle Invasive Urinary Bladder Cancer.

Invasive bladder cancer mortality remains high despite progresses made in early diagnosis and surgical procedures. Thus, there is a need to define new markers for bladder cancer. CLIC1 has not been previously studied in bladder cancer and thus, we aimed to assess its immunohistochemical expression in relation to different stages of bladder cancer development. Immunohistochemistry for CLIC1 was applied in 50 cases of muscle invasive bladder cancer. CLIC1 was not expressed in the normal urothelium, but a strong reaction was observed in dysplastic urothelium, carcinoma in situ and in 94% of the cases with invasive urothelial carcinoma; however, it was not expressed in squamous cell carcinoma cases. No correlation was found between the immunohistochemical expression of CLIC1 and the stage and grade of the tumour. CLIC1 was overexpressed in urinary bladder dysplastic epithelium, carcinoma in situ and invasive carcinoma. CLIC1 constitutes a new potential marker of invasive bladder cancer.

205P A study on organ preservation in muscle invasive urinary bladder cancer patients with intensity modulated radiotherapy and concurrent single agent cisplatin in south Indian population

The standard care for muscle invasive bladder carcinoma (MIBC) in the United States for a long time was radical cystectomy where as in Europe, it is radical radiotherapy or multidrug regimen neoadjuvant chemotherapy followed by radiotherapy. In spite of the importance in terms of incidence, prognosis and cost, bladder cancer research remains significantly underfunded so the studies and data on organ preservation in MIBC in India are less explored. We analyzed the data of 30 patients of MIBC from 2016-2018 who underwent primary transurethral resection of bladder tumour (TURBT) followed by IMRT with 64.8 Gy and weekly cisplatin at dose of 40 mg/ m2 with median follow up of 10 months. The role of various factors like tumour stage, histopathology, grade, complete TURBT, obstructive uropathy on locoregional response and disease free survival was evaluated. Local reactions evaluated using CTCAE criteria version 5.0. Statistical analysis was done using SPSS version 23.0. Table: 205PDemographic and disease characteristicsAgeMedian – 68 Yrs Range – 52 - 80 YrsSexMale – 86.7% (n=26) Female – 13.3% (n=4)TurbtComplete – 33.3% (n=10) Incomplete – 66.7% (n=20)HistopathologyTransitional – 86.6%(n=26) Squamous – 6.7% (n=2) Adeno CA – 6.7% (n=2)GradeGrade I – 6.7% (n=2) Grade II – 26.6% (n=8) Grade III - 66.7% (n=20)Tumour StageT2 – 53.3 % (n=16) T3 – 33.3 % (n=10) T4 – 13.4 % (n=4)Obstructive UropathyPresent – 33.3 % (n=10) Absent – 66.7% (n=20)Locoregional ResponseComplete – 73.3% (n=22) Partial – 20% (n=6) Progression – 6.7% (n=2) Open table in a new tab After the treatment, the complete locoregional response (LRR) was 73.3%. Early (T2 stage) tumours (p= 0.043) and patients without obstructive uropathy (p= 0.039) have shown significant LRR. Patients with complete TURBT, Low grade tumours shown increased response though statistically not significant. The overall disease free survival in this study for the preserved bladder patients is 53.3%. Patients without obstructive uropathy have shown significant DFS of 70% (p=0.026). Improved DFS of patients with T2 stage tumours (75%), complete TURBT (60%), low grade tumours was observed though statistically not significant. GU toxicities like dysuria, burning micturition in 40% of patients, increased frequency of micturition in 20% of patients, gastro intestinal toxicities like constipation (40%), pain abdomen (6.7%) were observed during followup and all these are grade I,II and managed well with supportive treatment. Bladder preservation in more than 70% of patients in this study supports the general concept of organ sparing treatment in oncology. The high response rate and DFS were observed in south Indians with complete TURBT, early stage tumours, no obstructive uropathy and low grade tumours. The genito urinary & gastro intestinal toxicities are comparatively less, probably in view of using IMRT technique and single agent cisplatin.

Mini-laparatomy radical cysto-prostatectomy for urinary bladder carcinoma

Introduction: Open radical cysto-prostatectomy (RCP) is the gold standard for invasive urinary bladder cancer in male. Though minimal invasive technique like laparoscopic or robotic assisted surgery is gaining popularity for surgical management in developed countries, open mini laparotomy is equally effective with similar oncological outcome and morbidity result. Our study aims to evaluate the feasibility of Mini-laparotomy RCP with ileal conduit (IC) or neobladder.&#x0D; Methods: This is a descriptive cross-sectional study of 25 patients conducted from October 2016 to December 2019. Nineteen patients had muscle invasive urinary bladder cancer (MIBC), four had multifocal high grade non-muscle invasive bladder cancer (NMIBC) and two were BCG failure patients. Nineteen patients underwent RCP with IC and six with RCP and ileal Neobladder. We analyzed technical difficulty, operative time, blood loss, peri-operative complication for minilaparotomy RCP.&#x0D; Results: The mean age of patients was 63.2 years (46-81years). The mean operative time was 274 minute (180-420 minutes) with mean blood loss of 470 ml (300-2000 ml). Mean post-operative ileus was observed for 2.8 days (2-4 days). All patients stayed in the hospital for mean days of 12.84 (7 to 25 days). All patients were mobilized early with mean intensive care unit (ICU) stay of 2.52 days. Mean lymph node extraction was 17.6. Two patients died of renal failure and hyperosmolar diabetes mellitus.&#x0D; Conclusion: Minilaparatomy RCP is a feasible option in terms of early recovery with acceptable morbidity without compromising the oncological principles.

Rare Occurrence of Chemotherapy-Induced Regression of Focal Nodular Hyperplasia: A Case Report and Literature Review

Background: Chemotherapy exerts a multitude of effects on all organ systems including the liver. Chemotherapyinduced liver changes are widely discussed in the literature and include hepatitis, hepatic steatosis, cholestasis, nodular hyperplasia, and veno-occlusive disease among others. The exact mechanism of which nodular hyperplasia is affected by chemotherapy is controversial but some experts suggest an alteration in blood supply might lead to exaggerated focal regeneration. Objectives: This study aimed to discuss an unusual effect of chemotherapeutic agents on pre-existing focal nodular hyperplasia with a short literature review. Patient and methods: A case report of 67 years old bedridden male patient presenting to the hospital with a 1- month history of gross hematuria who was treated with chemotherapy. Results: Our case showed an interval size reduction of a pre-treatment documented FNH in a patient with muscleinvasive urinary bladder cancer who was treated with a chemotherapy regimen of GemCarbo. This report also emphasizes the importance of enhanced MRI with hepatobiliary contrast agents in the evaluation of equivocal liver lesions in cancer patients to avoid misdiagnosis of distant metastasis. Conclusion: FNH is a common focal hepatic lesion and frequently seen in oncology patients during either initial evaluation or at follow up. Diagnostic radiologists should be aware of the expected imaging findings of various types of hepatic lesions and the effect of the medications the patient is receiving to avoid over-staging oncology patients.

Blood transfusions during neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer may have a negative impact on overall survival

Objective: To evaluate the extent and plausible effects of blood transfusions given during cisplatin-based neoadjuvant chemotherapy (NAC) on overall survival in patients with muscle-invasive urothelial bladder cancer (MIBC) undergoing NAC and radical cystectomy (RC).Background: Several studies have demonstrated a decreased survival for MIBC patients receiving allogenic peri- and postoperative blood transfusions in conjunction with RC. No studies have previously investigated the effects of blood transfusions during NAC.Materials and methods: 120 patients with MIBC (cT2-T4aN0M0) undergoing NAC and RC between 2008 and 2014 at four Swedish cystectomy centers were retrospectively evaluated. Clinicopathological data were obtained, including data of allogenic blood administration. Survival data was analyzed by Kaplan–Meier plotting and Cox regression.Results: One third of the cohort received blood transfusions during the period of NAC. In univariate analysis, blood transfusions during NAC, nodal stage and advanced tumor stage (pT >2) were negative prognostic factors for survival. In multivariate analysis, only pNx and pT >2 remained significant negative prognostic factors. In a subgroup analysis consisting of patients with localized tumors without dissemination (n = 96), patients that received transfusions during NAC showed an 18.5% absolute risk increase of death at five years of observation, although without statistical significance (p = .197).Conclusions: This is the first time that the extent and plausible effects of allogenic blood transfusions during NAC is examined in MIBC. Data suggest that there may be an association between blood transfusion and poor pathological and oncological outcome. Firm conclusions are difficult to draw due to few study participants and the retrospective nature of the study.

Delayed post-diuretic 18F-FDG PET/CT: can it help in determination of the best clinical decision for muscle invasive UB cancer patients?

Background18F-Fluorodeoxyglucose positron emission tomography-computed tomography (18F FDG PET/CT) has been used previously in the staging of the bladder cancer patients. Its main role was to detect regional nodal metastatic spread as well as distant organ metastasis but it was limited in detection of the primary neoplasia and the local tumor recurrence in the urinary bladder due to the presence of excreted radiotracer in the urinary tract, masking the urinary bladder lesion and probably the adjacent small regional metastatic lymph nodes. The aim of this study was to highlight the efficacy of delayed post-diuretic 18F-FDG PET/CT in staging and restaging muscle invasive urinary bladder cancer (MIBC), allowing metabolic evaluation of the primary disease, in addition to detection of associated metastasis which in turn can help to determine the best clinical decision for patients. This prospective study included 35 patients with MIBC, divided into two main groups: group A (18 patients) coming for initial staging and group B (17 patients) coming for post-therapeutic assessment. All patients of both groups were analyzed by a multidisciplinary team and the clinical decisions before and after PET CT were analyzed.ResultsIn group A, 7/18 patients were upstaged with consequent changing in therapeutic management. No downstaging was reported.In group B, the response was reported in 11/17 patients where they proceeded to radical surgery with an excellent agreement to pathological findings. 3/17 patients were stationary and 3/17 patients were progressed.PET/CT helped in the determination of the best treatment decision in 68.6% of patients among both groups.ConclusionDelayed post-diuretic PET/CT imaging is an important diagnostic tool in evaluation MIBC patients, which may consequently help to determinate the best clinical decision for them.

The increased risk for thromboembolism pre-cystectomy in patients undergoing neoadjuvant chemotherapy for muscle-invasive urinary bladder cancer is mainly due to central venous access: a multicenter evaluation

PurposeTo investigate if patients receiving neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) had an increased risk of thromboembolic events (TEE) and to evaluate when these events occur on a timeline starting from 6 months pre-cystectomy, during NAC-administration and 60 months post-cystectomy.MethodsTwo hundred and fifty five patients undergoing radical cystectomy during 2009–2014 at three Swedish cystectomy centers (Umeå, Linköping and Sundsvall) were in-detail reviewed retrospectively, using individual medical records. One hundred and twenty nine patients were ineligible for analysis. NAC patients (n = 67) were compared to NAC-naïve NAC-eligible patients (n = 59). The occurrence of TEE was divided into different periods pre-cystectomy and post-cystectomy. Statistical analyses included Chi-squared and logistical regression tests.ResultsSignificant associations were found between receiving NAC and acquiring a TEE during NAC therapy pre-cystectomy. All but one pre-cystectomy event was venous and all but one of the patients received NAC. 31% (14/45) of TEEs occurred pre-cystectomy. The incidence of TEEs pre-cystectomy in NAC-naive NAC-eligible patients was only 10% (2/20), whereas the incidence of TEEs in NAC patients occurred pre-cystectomy in 48% (12/25) and 11/12 incidents were detected during NAC therapy—this including 7/11 (64%) incidents affecting veins in anatomical conjunction with the placement of central venous access for chemotherapy administration.ConclusionsThere is a significantly increased risk for TEE pre-cystectomy during chemotherapy administration in MIBC patients receiving NAC, compared to the risk in NAC-naïve NAC-eligible MIBC patients. In 64% of the pre-RC TEEs in NAC patients, there was a clinical connection to placement of central venous access.

Follow-up surveillance of muscle-invasive urinary bladder cancer after curative treatment

Follow-up care of patients with muscle-invasive bladder cancer is subdivided into oncological and functional surveillance. More than 80% of local relapses and distant metastases occur within the first 2 years. Recurrences in the remnant urothelium also occur several years after radical cystectomy. Urinary cytology and acomputed tomography (CT) scan of the abdomen and thorax including a urography phase are the standard diagnostics for tumor follow-up. There is no clear evidence for asurvival benefit for the detection of asymptomatic vs. symptomatic recurrences. After partial cystectomy or trimodal treatment, there is no established follow-up schedule; however, the relatively high incidence of intravesical recurrences should be considered as there are curative treatment approaches including salvage cystectomy. Functional surveillance, which should be carried out lifelong, encompasses prevention and diagnostics of metabolic complications, urethral/ureteral strictures, problems with the urinary stoma, urinary incontinence, sexual dysfunction and urinary tract infections.

Naturally-occurring canine invasive urothelial carcinoma harbors luminal and basal transcriptional subtypes found in human muscle invasive bladder cancer.

There is growing evidence that molecular subtypes (e.g. luminal and basal subtypes) affect the prognosis and treatment response in patients with muscle invasive urinary bladder cancer (invasive urothelial carcinoma, iUC). Modeling these subtypes in pre-clinical animal studies is essential, but it is challenging to produce these subtypes, along with other critical host and tumor features, in experimentally-induced animal models. This study was conducted to determine if luminal and basal molecular subtypes are present in naturally-occurring canine iUC, a cancer that mimics the human condition in other key aspects. RNA sequencing was performed on 29 canine treatment naive iUC tissue samples and on four normal canine bladder mucosal samples. Data were aligned to CanFam 3.1, and differentially expressed genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups (n = 13, n = 16). When genes that distinguish basal and luminal subtypes in human cancer (n = 2015) were used to probe genes differentially expressed between normal canine bladder and iUC, 829 enriched signature genes were identified. Unsupervised hierarchical clustering of these genes revealed two distinct groups comprised of 18 luminal subtype tumors and 11 basal subtype tumors. The enriched genes included MMP9, SERPINE2, CAV1, KRT14, and RASA3 in basal tumors, and PPARG, LY6E, CTSE, CDK3, and TBX2 in luminal tumors. In supervised clustering, additional genes of importance in human iUC were identified in canine iUC associated with claudin-low and infiltrated tumors. A smaller panel of genes (n = 60) was identified that distinguished canine luminal and basal iUC with overall 93.1% accuracy. Immune signature patterns similar to those in human iUC were also identified with the greatest enrichment of immune genes being in the basal subtype tumors. These findings provide additional compelling evidence that naturally-occurring canine iUC is a highly relevant and much needed model of human iUC for translational research.

Effect of Nonurothelial Histologic Variants on the Outcomes of Radical Cystectomy for Nonmetastatic Muscle-invasive Urinary Bladder Cancer.

Knowledge of the comparative oncologic outcomes of histologic variants after radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) relies on small case series. We compared the effect of pure squamous cell carcinoma, adenocarcinoma, and neuroendocrine carcinoma compared with pure urothelial carcinoma (PUC) on overall survival (OS) and pathologic tumor, lymph node, and surgical margin status after RC. Using the National Cancer Database, we retrospectively examined patients undergoing RC for MIBC from 2003 to 2011. Our cohort was stratified according to histologic type and included only pure variants: squamous cell, adenocarcinoma, neuroendocrine, and PUC. Inverse probability weighting-adjusted and facility-clustered Cox and logistic regression analyses were used to assess the effect of histologic variants versus PUC on OS and pathologic outcomes. Overall, 475 (4.4%), 224 (2.1%), 155 (1.4%), and 10,033 (92.2%) patients underwent RC for MIBC with pure squamous cell carcinoma, adenocarcinoma, neuroendocrine carcinoma, and PUC, respectively. In inverse probability weighting-adjusted analyses, squamous cell (hazard ratio, 1.26; 95% confidence interval [CI], 1.07-1.49; P= .006) and neuroendocrine (hazard ratio, 1.53; 95% CI, 1.21-1.95; P< .001) types were associated with worse OS relative to PUC. Squamous cell carcinoma (odds ratio [OR], 1.58; 95% CI, 1.23-2.04; P< .001), adenocarcinoma (OR, 1.49; 95% CI, 1.04-2.14; P= .030), and neuroendocrine carcinoma (OR, 2.37; 95% CI, 1.58-3.55; P< .001) at diagnosis were associated with greater odds of≥ pT3 disease. The squamous cell and neuroendocrine variants were associated with decreased (OR, 0.66; 95% CI, 0.48-0.91; P= .012) and increased (OR, 1.58; 95% CI, 1.06-2.37; P= .026) odds of pN+ disease, respectively. Adenocarcinoma was associated with greater odds of positive margins (OR, 2.14; 95% CI, 1.39-3.30; P= .001). Pure squamous cell and neuroendocrine carcinoma histologic types were associated with worse OS relative to PUC. However, no difference was found between adenocarcinoma and PUC. All histologic variants were associated with higher tumor stage at surgery compared with PUC.