Dataset Information

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

ABSTRACT:

Purpose

To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC).

Materials and methods

We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer Genome Atlas (TCGA) to investigate the prevalence of TCGA molecular subtypes and DNA damage repair (DDR) gene alterations according to patient age.

Results

pOR was achieved in 40% of patients. There was no difference in distribution of pOR or pCR between age quartiles. On univariable logistic regression analysis, patient age was not associated with pOR or pCR when evaluated as continuous variables or stratified in quartiles (all p > 0.3). Median follow-up was 18 months (IQR 6-37). On Cox regression and competing risk regression analyses, age was not associated with survival outcomes (all p > 0.05). In the TCGA cohort, patient with age ≤ 60 years has 7% less DDR gene mutations (p = 0.59). We found higher age distribution in patients with luminal (p < 0.001) and luminal infiltrated (p = 0.002) compared to those with luminal papillary subtype.

Conclusions

While younger patients may have less mutational tumor burden, our analysis failed to show an association of age with response to preoperative chemotherapy or survival outcomes. Therefore, the use of preoperative chemotherapy should be considered regardless of patient age.

SUBMITTER: D'Andrea D

PROVIDER: S-EPMC8602146 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

D'Andrea David D Black Peter C PC Zargar Homayoun H Zargar-Shoshtari Kamran K Soria Francesco F Fairey Adrian S AS Mertens Laura S LS Dinney Colin P CP Mir Maria C MC Krabbe Laura-Maria LM Cookson Michael S MS Jacobsen Niels-Erik NE Montgomery Jeffrey S JS Vasdev Nikhil N Yu Evan Y EY Xylinas Evanguelos E Campain Nicholas J NJ Kassouf Wassim W Dall'Era Marc A MA Seah Jo-An JA Ercole Cesar E CE Horenblas Simon S Sridhar Srikala S SS McGrath John S JS Aning Jonathan J Wright Jonathan L JL Thorpe Andrew C AC Morgan Todd M TM Holzbeierlein Jeff M JM Bivalacqua Trinity J TJ North Scott S Barocas Daniel A DA Lotan Yair Y Grivas Petros P Stephenson Andrew J AJ Shah Jay B JB van Rhijn Bas W BW Daneshmand Siamak S Spiess Philippe E PE Shariat Shahrokh F SF

World journal of urology 20210809 12

<h4>Purpose</h4>To assess the association of patient age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer (MIBC).<h4>Materials and methods</h4>We analyzed data from 1105 patients with MIBC. Patients age was evaluated as continuous variable and stratified in quartiles. Pathologic objective response (pOR; ypT0-Ta-Tis-T1N0) and pathologic complete response (pCR; ypT0N0), as well survival outcomes were assessed. We used data of 395 patients from The Cancer G ...[more]

PMID: 34370078

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Project description:BackgroundThe recommended treatment for patients with non-metastatic muscle-invasive bladder cancer (MIBC) is neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). Following NAC, 20-40% of patients experience a complete pathological response (pCR) in the RC specimen and these patients have excellent long-term overall survival. Subject to debate is, however, whether patients with a pCR to NAC benefit from RC, which is a major surgical procedure with substantial morbidity, and if these patients might be candidates for close surveillance instead. However, currently it is not possible to accurately identify patients with a pCR to NAC in whom RC might be withheld. The objective of this study is to assess whether pathological response in the RC specimen after NAC can be predicted based on clinical, radiological, and histological variables and on a wide set of molecular biomarkers assessed in tissue, blood and urine.MethodsThis is a multicentre, prospective cohort study, including patients with cT2a-T4a N0-N1 M0 urothelial cell MIBC who are scheduled to undergo cisplatin-based NAC followed by RC. Prior to start of therapy, a 2-Deoxy-2-[18F] fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) is performed. Response to NAC is evaluated by CT-scan. Blood and urine, including cytology, are prospectively collected for biomarker analyses before and after NAC. Immediately before RC, participants undergo cystoscopy with bimanual examination and a re-staging transurethral resection (TUR) of all visible cancerous lesions or with biopsies from scar tissue. Subsequently, RC is performed in all patients. Tissue from the diagnostic TUR, the re-staging TUR, and the RC specimen is examined for the presence of urothelial cancer carcinoma and DNA and RNA is isolated for molecular analysis. The primary endpoint is the pathological stage (ypTN) in the RC and ePLND specimen and its association with clinical response.DiscussionIf the PRE-PREVENCYS trial shows that the absence of residual disease after NAC in patients with MIBC is accurately predicted, a randomized controlled trial is scheduled comparing the overall survival of NAC plus RC versus NAC followed by close surveillance for patients with a clinically complete response (PREVENCYS trial).Trial registrationNetherlands Trial Register: NL8678; Registered 20 May 2020 https://www.trialregister.nl/trial/8678.

Project description:Background and aimNeoadjuvant chemotherapy (NAC) followed by radical cystectomy is the current gold standard treatment for muscle-invasive urothelial bladder cancer (MIBC). Nonetheless, some MIBC patients showed limited pathological response after NAC. Herein, we used whole-exome sequencing (WES) to identify genetic mutations in MIBC that can predict NAC response.MethodsForty MIBC patients were enrolled in this study, in which 33 were successfully examined by WES and Sanger sequencing in the discovery cohort (n=13) and the validation cohort (n=20), respectively. ANNOVAR software was used to identify the potential mutations based on the data of WES. In addition, tumor-specific somatic mutations including single nucleotide variants and indels were called with the muTECT and Strelka software. The mutational analysis of specific genes was carried out based on the data from cBioPortal for Cancer Genomics.ResultsIn the discovery cohort, the mutation frequencies of TP53, MED16, DRC7, CEND1, ATAD5, SETD8, and PIK3CA were significantly higher in 13 MIBC patients. Specifically, the presence of somatic mutations of APC, ATM, CDH9, CTNNB1, METTL3, NBEAL1, PTPRH, RNASEL, and FBXW7 in NAC responder signifies that these mutations were potential predictors of pathological response to NAC. Furthermore, somatic mutations of CCDC141, PIK3CA, CHD5, GPR149, MUC20, TSC1, and USP54 were exclusively identified in NAC nonresponders, suggesting that these mutations may participate in the process of NAC resistance. In the validation cohort, the somatic mutations of CDH9, METTL3, and PTPRH were significantly enriched in NAC responders while the somatic mutation of CCDC141 was significantly enriched in NAC nonresponders. Furthermore, survival analysis revealed that the patients expressing mutated METTL3 have a longer overall survival and disease- or progression-free survival than the patients acquiring wild-type METTL3.ConclusionThe somatic mutation of METTL3 can be a potential predictive biomarker of NAC response in MIBC patients.Relevance for patientsMIBC patients bearing mutated METTL3 display a pathological response to NAC and have a significantly longer overall survival or disease/progression-free survival as compared to the patients bearing wild-type METTL3. Thus, the somatic mutation of METTL3 is a potential biomarker for predicting response to NAC in MIBC patients, assisting doctors in making the clinical decision.

Dataset Information

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

Purpose

Materials and methods

Results

Conclusions

Publications

Association of age with response to preoperative chemotherapy in patients with muscle-invasive bladder cancer.

Similar Datasets

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