Neoadjuvant chemotherapy and bladder-sparing surgery for invasive bladder cancer: ten-year outcome.

1998 ◽  
Vol 16 (4) ◽  
pp. 1298-1301 ◽  
Author(s):  
H W Herr ◽  
D F Bajorin ◽  
H I Scher
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Bladder Tumor ◽  
Tumor Node Metastasis ◽  
Bladder Tumors ◽  
Primary Tumor Site ◽  
Node Metastasis ◽  
Bladder Sparing ◽  
Salvage Cystectomy

PURPOSE To evaluate the 10-year outcome of patients with invasive (T2-3N0M0, staged according to the tumor, node, metastasis system) bladder cancer who responded completely to a combination of methotrexate, vinblastine, adriamycin, and cisplatin (MVAC) chemotherapy followed by bladder-sparing surgery. PATIENTS AND METHODS Of 111 surgical candidates who received neoadjuvant MVAC, 60 (54%) achieved a complete clinical response (T0) on transurethral resection (TUR) of the primary tumor site. Of these, 28 requested follow-up with TUR alone, 15 had a partial cystectomy, and 17 elected a radical cystectomy. The patients were followed up for a median of 10 years (range, 8 to 13 years). RESULTS Of 43 patients who had bladder-sparing surgery, 32 (74%) are alive, which includes 25 (58%) with an intact functioning bladder. Twenty-four patients (56%) developed bladder tumor recurrences from 5 to 96 months, which were invasive in 13 (30%) and superficial in 11 (26%). Thirteen patients required a salvage cystectomy, of whom 6 died, which includes 4 (9%) from a new invasive neoplasm. Of the 17 patients who had radical cystectomy, 11 (65%) are alive. CONCLUSION The majority of patients with invasive bladder tumors who achieve T0 status after neoadjuvant MVAC chemotherapy preserve their bladders for up to 10 years with bladder-sparing surgery. The bladder remains at risk for new invasive tumors. Cystectomy salvages the majority, but not all, of relapsing patients.

Absence of Tumor on Repeat Transurethral Resection of Bladder Tumor Does Not Predict Final Pathologic T0 Stage in Bladder Cancer Treated with Radical Cystectomy

2018 ◽  
Vol 4 (5) ◽  
pp. 720-724 ◽  
Author(s):  
Janet Baack Kukreja ◽  
Sima Porten ◽  
Vishnukamal Golla ◽  
Philip Levy Ho ◽  
Graciela Noguera-Gonzalez ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Transurethral Resection ◽  
Bladder Tumor

scholarly journals Urine tumor DNA detection of minimal residual disease in muscle-invasive bladder cancer treated with curative-intent radical cystectomy: A cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (8) ◽  
pp. e1003732
Author(s):  
Pradeep S. Chauhan ◽  
Kevin Chen ◽  
Ramandeep K. Babbra ◽  
Wenjia Feng ◽  
Nadja Pejovic ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Radical Cystectomy ◽  
Residual Disease ◽  
Muscle Invasive Bladder Cancer ◽  
Curative Intent ◽  
Muscle Invasive ◽  
Bladder Sparing ◽  
Tumor Dna ◽  
Minimal Residual

Background The standard of care treatment for muscle-invasive bladder cancer (MIBC) is radical cystectomy, which is typically preceded by neoadjuvant chemotherapy. However, the inability to assess minimal residual disease (MRD) noninvasively limits our ability to offer bladder-sparing treatment. Here, we sought to develop a liquid biopsy solution via urine tumor DNA (utDNA) analysis. Methods and findings We applied urine Cancer Personalized Profiling by Deep Sequencing (uCAPP-Seq), a targeted next-generation sequencing (NGS) method for detecting utDNA, to urine cell-free DNA (cfDNA) samples acquired between April 2019 and November 2020 on the day of curative-intent radical cystectomy from 42 patients with localized bladder cancer. The average age of patients was 69 years (range: 50 to 86), of whom 76% (32/42) were male, 64% (27/42) were smokers, and 76% (32/42) had a confirmed diagnosis of MIBC. Among MIBC patients, 59% (19/32) received neoadjuvant chemotherapy. utDNA variant calling was performed noninvasively without prior sequencing of tumor tissue. The overall utDNA level for each patient was represented by the non-silent mutation with the highest variant allele fraction after removing germline variants. Urine was similarly analyzed from 15 healthy adults. utDNA analysis revealed a median utDNA level of 0% in healthy adults and 2.4% in bladder cancer patients. When patients were classified as those who had residual disease detected in their surgical sample (n = 16) compared to those who achieved a pathologic complete response (pCR; n = 26), median utDNA levels were 4.3% vs. 0%, respectively (p = 0.002). Using an optimal utDNA threshold to define MRD detection, positive utDNA MRD detection was highly correlated with the absence of pCR (p < 0.001) with a sensitivity of 81% and specificity of 81%. Leave-one-out cross-validation applied to the prediction of pathologic response based on utDNA MRD detection in our cohort yielded a highly significant accuracy of 81% (p = 0.007). Moreover, utDNA MRD–positive patients exhibited significantly worse progression-free survival (PFS; HR = 7.4; 95% CI: 1.4–38.9; p = 0.02) compared to utDNA MRD–negative patients. Concordance between urine- and tumor-derived mutations, determined in 5 MIBC patients, was 85%. Tumor mutational burden (TMB) in utDNA MRD–positive patients was inferred from the number of non-silent mutations detected in urine cfDNA by applying a linear relationship derived from The Cancer Genome Atlas (TCGA) whole exome sequencing of 409 MIBC tumors. We suggest that about 58% of these patients with high inferred TMB might have been candidates for treatment with early immune checkpoint blockade. Study limitations included an analysis restricted only to single-nucleotide variants (SNVs), survival differences diminished by surgery, and a low number of DNA damage response (DRR) mutations detected after neoadjuvant chemotherapy at the MRD time point. Conclusions utDNA MRD detection prior to curative-intent radical cystectomy for bladder cancer correlated significantly with pathologic response, which may help select patients for bladder-sparing treatment. utDNA MRD detection also correlated significantly with PFS. Furthermore, utDNA can be used to noninvasively infer TMB, which could facilitate personalized immunotherapy for bladder cancer in the future.

scholarly journals Preoperative Serum Gamma-Glutamyltransferase as a Prognostic Biomarker in Patients Undergoing Radical Cystectomy for Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shiqiang Su ◽  
Lizhe Liu ◽  
Chao Sun ◽  
Yanhua Nie ◽  
Hong Guo ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Radical Cystectomy ◽  
Elevated Serum ◽  
Disease Free Survival ◽  
Prognostic Models ◽  
Lymph Node Status ◽  
Cancer Specific Survival ◽  
Gamma Glutamyltransferase ◽  
Preoperative Serum

BackgroundSerum gamma-glutamyltransferase (GGT) has been reported to be correlated with survival in a variety of malignancies. However, its effect on patients with bladder cancer (BC) treated by radical cystectomy has never been evaluated.Patients and MethodsWe retrospectively evaluated 263 patients who underwent radical surgery in our center. Baseline features, hematologic variables, and follow-up data were obtained. The endpoints included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). The relationship between GGT and survival were evaluated.ResultsThe median follow-up period for all patients was 34.7 (22.9-45.9) months. At the last follow-up, 67 patients died, 51 patients died of cancer, 92 patients experienced disease recurrence. Patients with an elevated serum GGT had a higher rate of pT3-T4 tumors. Patients with a higher preoperative serum GGT had a lower rate of OS, CSS and DFS (P &lt; 0.001 for all). Multivariate analysis identified that preoperative serum GGT was independent predictor of OS (HR: 3.027, 95% CI: 1.716-5.338; P &lt; 0.001), CSS (HR: 2.115, 95% CI: 1.093-4.090; P = 0.026), DFS (HR: 2.584, 95% CI: 1.569-4.255; P &lt; 0.001). Age, diabetes history, pathologic T stage, and lymph node status also were independent predictors of prognosis for BC patients.ConclusionsOur results indicated that preoperative serum GGT was an independent prognosis predictor for survival of BC patients after radical cystectomy, and can be included in the prognostic models.

A modified ileal conduit technique in patients undergoing radical cystectomy: Single-centre experience

2021 ◽  
pp. 205141582110414
Author(s):  
Francesco Chiancone ◽  
Francesco Persico ◽  
Marco Fabiano ◽  
Maurizio Fedelini ◽  
Clemente Meccariello ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Postoperative Complications ◽  
Blood Loss ◽  
Radical Cystectomy ◽  
Ileal Conduit ◽  
Intraoperative Complications ◽  
Perioperative Outcomes ◽  
Multivariate Logistic Regression Model ◽  
Increased Risk

Objective: We aimed to evaluate perioperative outcomes and complications of a modified technique of ileal conduit diversion. Methods: Forty-seven cases of radical cystectomy with modified ileal conduit diversion were performed at our institution from January 2015 to January 2020. After radical cystectomy, a segment of ileum was used to pack the conduit and was placed below the digestive anastomosis. Then, the mesentery window of the ileo-ileal anastomosis was sutured. The ureters were anastomosed on their native side on single loop ureteral stents. All procedures were performed by a single surgical team. Intra- and postoperative complications were classified and reported according to the Satava and Clavien–Dindo grading systems. Results: The mean age of population was 66.40±10.14 years, and 76.6% were male. Concomitant diabetes was found in 31.9% of patients. About three quarters of patients had T2G3 bladder cancer. Mean blood loss was 449.36±246.50 ml, and hospitalization was 10.32±5 days. With a mean follow-up of 17.36±12.63 months, the recurrence rate was 17%, and 14.9% of patients died of bladder cancer. Out of the 47 patients, three (4.3%) experienced intraoperative complications, while 15 (31.9%) had postoperative complications. Of these, only three patients experienced Clavien–Dindo complications ⩾grade 3. Multivariate logistic regression model showed that diabetes ( p=0.023) and higher blood loss ( p=0.010) were significantly associated with an increased risk of postoperative complications. We reported one case of ureterointestinal anastomosis stenosis on the left side and none on the right side. Despite our results being promising, larger randomized trials with longer follow-up are needed to explore further the feasibility of this technique on a larger scale. Conclusion: We describe a safe and simple surgical technique with a similar postoperative complications rate and a lower incidence of ureteroileal anastomosis stenosis compared to the standard technique. Level of evidence 4.

scholarly journals Impact of BRAF V600E and TERT Promoter Mutations on Response to Therapy in Papillary Thyroid Cancer

Endocrinology ◽  
2019 ◽  
Vol 160 (10) ◽  
pp. 2328-2338 ◽  
Author(s):  
Tomasz Trybek ◽  
Agnieszka Walczyk ◽  
Danuta Gąsior-Perczak ◽  
Iwona Pałyga ◽  
Estera Mikina ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Response To Therapy ◽  
Braf V600e ◽  
Papillary Thyroid ◽  
Tumor Node Metastasis ◽  
Node Metastasis ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract In this study, we examined the relationship between coexisting BRAF V600E and TERT promoter mutations in papillary thyroid cancer (PTC) and response to therapy. PTC cases (n = 568) with known BRAF and TERT status, diagnosed from 2000 to 2012 and actively monitored at one institution, were reviewed retrospectively. Associations between BRAF V600E and TERT promoter mutations and clinicopathological features, Tumor-Node-Metastasis stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association 2015 criteria and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system. Median follow-up was 120 months. TERT promoter mutations (any type) were detected in 13.5% (77/568) of PTC cases with known BRAF status. The C228T and C250T TERT hotspot mutations were found in 54 (9.5%) and 23 (4%) patients, respectively, and 22 other TERT promoter alterations were identified. Coexisting BRAF V600E and TERT hotspot promoter mutations were detected in 9.5% (54/568) of patients, and significantly associated with older patient age (P = 0.001), gross extrathyroidal extension (P = 0.003), tumor stage pT3-4 (P = 0.005), stage II to IV (P = 0.019), intermediate or high initial risk (P = 0.003), worse than excellent response to primary therapy (P = 0.045), recurrence (P = 0.015), and final outcome of no remission (P = 0.014). We conclude that coexisting BRAF V600E and TERT mutations in patients with PTC are associated with poor initial prognostic factors and clinical course and may be useful for predicting a worse response to therapy, recurrence, and poorer outcome than in patients without the above mutations.

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