Impact of KRAS alterations in localized pancreatic cancer (PC).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 431-431
Author(s):  
Aditya Varnam Shreenivas ◽  
Kaitlin Annunzio ◽  
Mandana Kamgar ◽  
Sakti Chakrabarti ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Metastatic Disease ◽  
Primary Tumor ◽  
Locally Advanced ◽  
Kras Mutations ◽  
Cox Regression Analysis ◽  
Kras Status ◽  
Localized Disease ◽  
The Individual ◽  
The Impact ◽  
Codon 61

431 Background: Patients (pts) with localized PC do not routinely undergo comprehensive genomic profiling (CGP) unless they develop recurrent or metastatic disease. KRAS is the most frequently mutated gene in PC, however, the impact of different KRAS mutations in localized PC has not been well characterized. We interrogated our genomic database to analyze the KRAS status in PC pts who presented with localized disease at diagnosis (Dx). Methods: We identified PC pts at our institution who underwent CGP utilizing the Foundation One CDx assay and had localized disease at initial Dx; these pts were categorized into resectable/borderline resectable PC (LPC) and locally advanced PC (LAPC). All pts with LPC and LAPC underwent neoadjuvant chemotherapy and chemoradiation prior to possible surgery (all intended therapy - AIT). Tissue from metastatic sites was used for CGP in pts who developed recurrent/metastatic disease before or after completion of AIT. The primary tumor was used for CGP in pts who completed AIT without subsequent relapse or in the absence of adequate metastatic tissue. Effect of each gene on response and survival outcomes was estimated using proportional odds and Cox regression analysis, respectively, adjusting for stage. Results: 75 pts were identified, median age at Dx was 65 years, 59% were male, 65% had a primary tumor in the pancreatic head. 38 (86%) pts with LPC completed AIT compared to 21 (68%) pts with LAPC (p<0.001). KRAS mutation was detected in 95% (71/75) of pts– 94% (67/71) in codon 12 and 6% (4/71) in codon 61. The various KRAS mutations and their association with completion of AIT is summarized in the table. The likelihood of completing AIT did not differ based on KRAS wildtype (WT) vs mutated status (p =1.00), the mutated codon (codon 12 vs. codon 61; p =1.00) or the individual KRAS point mutations (p = 0.7); however, all patients with G12A (N= 1), G12C (N=1), G12L (N=1) and G12R (N=11) mutations completed AIT. KRAS status (mutated vs. WT) and the individual KRAS mutations were not associated with overall survival (OS) after adjusting for stage (p= 0.13 and p = 0.26 respectively). Median OS for patients with LPC and LAPC, was 39 months (mos) and 29 mos respectively. Conclusions: KRAS status and individual KRAS mutations did not have an impact on completing AIT or mOS; however, these findings need to be interpreted with caution due to the inherent biases involved in such analyses. The clinical significance and functional relevance of KRAS G12A, G12C, G12L and G12R mutations, though relatively rare, needs further characterization as well as mechanistic elucidation. [Table: see text]

The impact of lung and bone metastases on prognosis in advanced PDAC.

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 494-494
Author(s):  
Grainne M. O'Kane ◽  
Adriana Fraser ◽  
Stephanie Moignard ◽  
Anna Dodd ◽  
Sean Creighton ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Ductal Adenocarcinoma ◽  
Peritoneal Disease ◽  
Cox Regression Analysis ◽  
Cytotoxic Treatment ◽  
The Impact

494 Background: Pancreatic ductal adenocarcinoma (PDAC) remains a highly fatal disease inherently resistant to cytotoxic treatment. Despite the prevalence of liver and peritoneal metastases, subsets of patients also develop lung and bone metastases highlighting phenotypic heterogeneity. We reviewed the prognostic implications of metastatic sites on survival. Methods: This retrospective cohort study included all patients with PDAC who received surgical or oncological treatment at the University Health Network from September 2012 until December 2016. Clinical and pathological variables were obtained from patient electronic records. Radiological images and pathology reports were reviewed to ascertain sites of metastatic disease. The Kaplan-Meier method for survival and multivariable cox regression analysis identified prognostic factors. Results: 1153 patients were reviewed and 985 were included. 55% were male and the median age at diagnosis was 67 years. 287 (29%) completed curative surgery and 698 (71%) had locally advanced or metastatic disease; the median survival was 22 months and 9 months respectively. Lung and bone metastases were present in 18% (N = 180) and 6% (N = 58) of patients. In multivariable analysis increasing age and stage at diagnosis correlated with inferior survival (p < 0.0001) and the presence of any lung (HR 0.77; 95% CI 0.63-0.94, p = 0.01) or bone metastases (HR 0.74; 95% CI 0.54-1.0, p = 0.05) resulted in improved outcomes. Liver and peritoneal disease were not prognostic. Sex and family history of PDAC did not associate with survival. There was no association between site of metastases and sex however patients with bone metastases were significantly younger at first diagnosis (median age 63yrs, p < 0.01). Conclusions: Patients with advanced PDAC and metastases to lung or bone may represent distinct biological subtypes of PDAC. Molecular profiling of available tissue is ongoing.

scholarly journals No Correlation between KRAS Status and Advanced Pancreatic Adenocarcinoma Survival

2017 ◽  
Vol 6 (2) ◽  
pp. 45 ◽  
Author(s):  
Misato Ogata ◽  
Hironaga Satake ◽  
Takatsugu Ogata ◽  
Yukihiro Imai ◽  
Yukimasa Hatachi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Growth Factor Receptor ◽  
Gene Mutations ◽  
Progression Free Survival ◽  
Patient Characteristics ◽  
Predictive Biomarker ◽  
First Line ◽  
Kras Mutations ◽  
Kras Status ◽  
The Impact

Erlotinib plus gemcitabine is one of the standard chemotherapies for unresectable pancreatic cancer. Pancreatic cancer has the highest frequency of KRAS gene mutations among human cancers, and some studies suggest that KRAS status might be a predictive biomarker for anti-epidermal growth factor receptor treatment. However, the reliability of this biomarker has not been confirmed. Here, we evaluated the impact of KRAS mutations in pancreatic cancer patients treated with first line gemcitabine-based chemotherapy. 23 patients treated with gemcitabine-based chemotherapy whose KRAS status could be examined from primary or metastatic lesions were enrolled. KRAS mutations were analyzed by sequencing codons 12 and 13. We retrospectively evaluated the correlation between KRAS status, and prognosis and treatment efficacy. Patient characteristics were as follows: median age 68 years, male/female=6/17, PS 0/1=9/14, TNM stage III/IV=1/22, and gemcitabine alone/erlotinib plus gemcitabine=13/10. Among the 23 patients, KRAS codon 12 was mutated in 15, one of whom also had mutation on codon 13. Median progression-free survival (PFS) and overall survival (OS) of all patients were 4.3 months (95% confidence interval (CI): 3.1 to 5.4) and 8.1 months (95% CI: 5.9 to 10.0; events in 96%), respectively. KRAS status showed no association with PFS (p=0.310), OS (p=0.934), or the efficacy of treatment with (p=0.833) or without erlotinib (p=0.478). Thus, in this study, there was no correlation between KRAS status and the efficacy of first line chemotherapy with gemcitabine with or without erlotinib. Identification of a rationale for personalized medicine in pancreatic cancer will require further exploratory prospective studies.

Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial

2011 ◽  
Vol 29 (20) ◽  
pp. 2773-2780 ◽  
Author(s):  
Carlo Aschele ◽  
Luca Cionini ◽  
Sara Lonardi ◽  
Carmine Pinto ◽  
Stefano Cordio ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Primary Tumor ◽  
Tumor Response ◽  
Locally Advanced ◽  
Muscularis Propria ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Iii ◽  
Preoperative Treatment ◽  
The Impact

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

Prognostic significance of ki67, p53, TS and EGFR in advanced gastric and gastroesophageal junction cancer patients treated with cetuximab plus FOLFIRI (FOLCETUX study)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4604-4604 ◽  
Author(s):  
F. L. Rojas Llimpe ◽  
F. Di Fabio ◽  
C. Ceccarelli ◽  
C. Pinto ◽  
S. Siena ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Metastatic Disease ◽  
Gastroesophageal Junction ◽  
Objective Response ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Neoplastic Cell ◽  
Exact Test ◽  
Egfr Expression ◽  
The Impact

4604 Background: The aim of this study was to evaluate the correlation between pathologic biomarkers and objective response (OR), time to progression (TTP) and overall survival (OS) in advanced gastric or gastroesophageal junction (GEJ) cancer patients (pts) treated with cetuximab plus FOLFIRI. Methods: We analysed 32/38 pts with stomach or GEJ locally advanced/metastatic adenocarcinoma, EGFR+, enrolled in the Italian FOLCETUX study. The pts were treated as first line with cetuximab weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, plus FOLFIRI every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Expression of Ki67, p53, TS and EGFR was examined immunohistochemically in primary tumor and/or metastasis samples. Ki67, p53 and TS were categorized into a low and high value; EGFR was categorized into low, intermediate and high values. High cut-off was defined as: >50% Ki67; >20% p53; =9% cytoplasmatic and >30% nuclear TS; EGFR score (combining % neoplastic cell positive and intensity) was: low=0–2, intermediate=3–5, high=6–7. To avoid any discrepant evaluation the assessment was carried out centrally by just one pathologist. Results: The pt characteristics were: 22M/10F; median age 64.5 years (39–83); stomach 29(90.6%), GEJ 3(9.4%); intestinal histotype 21(65.6%), non-intestinal 11(34.4%); locally advanced disease 4(12.5%), metastatic disease 28(87.5%). The OR were: 15 CR+PR, 15 SD, 2 PD. No relationship was observed between Ki67, p53, TS and EGFR expression and OR (Chi-squared test/Fisher’s Exact Test). In the multivariate analysis adjusted for the impact of intestinal/non-intestinal histotype and locally advanced/metastatic disease, the low TS expression was associated with an improved TTP ( Table 1 ). Conclusions: This results suggest that TS, EGFR, p53 and Ki67 expressions are not significantly correlated with OR. Low TS expression is predictive of better TTP. [Table: see text] No significant financial relationships to disclose.

Transcriptional characterization of immune microenvironment and their prediction role for the prognosis of local advanced lung adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20625-e20625
Author(s):  
Yuqiao Chen ◽  
Xinying Shi ◽  
Xue Song ◽  
Lingling Gao ◽  
Beibei Mao ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Survival Data ◽  
Primary Tumor ◽  
Antigen Processing ◽  
Early Stage ◽  
Locally Advanced ◽  
Immune Microenvironment ◽  
Immune Related Genes ◽  
The Impact ◽  
Local Advanced

e20625 Background: The resection of early stage NSCLC offers patients the best hope of a cure. However, the recurrence rate post-resection remains high. As the mechanisms involved in the process is still not clear due to the unavailability of accurate targets, our study was aimed to integrate the impact of different immune context present in lung adenocarcinoma (LUAD) microenvironment on patients’ prognosis. Methods: RNA targeted sequencing was performed on 24 primary tumor specimens from the resected local advanced LUADs . Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The limma package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the prognosis (PFS, progression free survival) post-resection. Results: 23 DEGs were detected in primary tumor between the better (PFS > 18months, n = 12 ) and worse (PFS≤18months, n = 12 ) prognosis group. The combined prediction model containing MPO, IL-6, CXCR2, FCGR3B, ADGRE5 could identify the favorable prognosis of patients. GSVA and Log Rank test of survival data demonstrated that the antigen processing and lymphocyte activation pathway enrichment may associate with better prognosis (p = 0.01), whereas higher Neutrophils cell infiltration in primary tumor demonstrated a shorter PFS (p = 0.008). Conclusions: In LUAD, the immune related genes such as MPO, IL-6, CXCR2, FCGR3B, ADGRE5, can effectively profile the landscape of tumor immune microenvironment and predict the survival in early stage of lung adenocarcinoma. Accordingly immune pathways were correlated with prognosis of these patients. Our findings suggest that immune-related RNA expression pattern in locally advanced LUAD may provide a potential predictive marker for early recurrence after surgical resection.

CARD: Overall survival (OS) analysis of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving cabazitaxel versus abiraterone or enzalutamide.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5569-5569
Author(s):  
Bertrand F. Tombal ◽  
Daniel Castellano ◽  
Gero Kramer ◽  
Jean-Christophe Eymard ◽  
Johann S. De Bono ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Metastatic Disease ◽  
Cox Regression ◽  
Castration Resistant Prostate Cancer ◽  
Cox Regression Analysis ◽  
Previously Treated ◽  
Alternative Art ◽  
Daily Prednisone ◽  
The Impact

5569 Background: The CARD trial (NCT02485691) compared cabazitaxel vs. an androgen receptor targeted agent (ART; abiraterone/enzalutamide) in mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), in any order. These post hoc analyses assessed OS from various time points and the impact of prognostic factors. Methods: Patients with mCRPC previously treated with docetaxel and progressing ≤ 12 months on prior abiraterone/enzalutamide were randomized 1:1 to cabazitaxel (25 mg/m2 IV Q3W + daily prednisone + prophylactic G-CSF) vs. abiraterone (1000 mg PO + daily prednisone) or enzalutamide (160 mg PO). OS was calculated from date of diagnosis of metastatic disease, date of mCRPC, and start of 1st, 2nd or 3rd life-extending therapy (LET). A stratified multivariate Cox regression analysis assessed the impact of 14 prognostic factors on OS using a stepwise model selection approach with a significance level of 0.10 for entry into the model and 0.05 for removal. Results: In the CARD study (N = 255), median OS was longer with cabazitaxel vs. abiraterone/enzalutamide (13.6 vs 11.0 months; HR 0.64, 95% CI 0.46–0.89; p = 0.008). OS was numerically improved for cabazitaxel vs. abiraterone/enzalutamide when assessed from the time of diagnosis of metastatic disease or mCRPC, or from start of 1st or 2nd LET (Table). In the multivariate analysis, low hemoglobin, high baseline neutrophil to lymphocyte ratio, and high PSA values at baseline were associated with worse OS. In presence of these factors, the OS benefit observed with cabazitaxel versus abiraterone/enzalutamide remained significant (HR 0.63, 95% CI 0.42–0.94, p = 0.022). Conclusions: Cabazitaxel numerically improved OS vs. abiraterone/enzalutamide in patients with mCRPC previously treated with docetaxel and the alternative ART (abiraterone/enzalutamide), whatever the time point considered. The robustness of this OS benefit was confirmed by stratified multivariate analysis. Sanofi funded. Clinical trial information: NCT02485691 . [Table: see text]

Prognostic impact of local therapy of the primary tumor in metastatic breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1114-1114
Author(s):  
Isabelle Katrin Himsl ◽  
Nina Ditsch ◽  
Miriam Susanne Lenhard ◽  
Jutta Engel ◽  
Michael Untch ◽  
...  
Keyword(s):  
Stem Cells ◽  
Metastatic Disease ◽  
Primary Tumor ◽  
Univariate Analysis ◽  
Local Treatment ◽  
Local Therapy ◽  
Prognostic Impact ◽  
Tumor Stem Cells ◽  
Receptor Status ◽  
The Impact

1114 Background: MBC is an incurable disease and the treatment aims are palliative. It is not known whether the difference in OS is the result of a selection bias or caused by dissemination of tumor stem cells in pat. without surgery. Methods: To identify the impact of surgical therapy of the primary tumor, a mono-institutional retrospective review from 1990-2006 was done in primary MBC pts. Results: We identified 269 pts. with primary MBC, 63 of whom had received no surgical local treatment. Mean follow up is 65 m for pts., observed mortality 87%. Location of metastases were bone only (36%), visceral or soft tissue (one organ only, 19%), multiple organs (40%) and including CNS metastases (5%). 50% had G3 tumors, 25% negative receptor status, 7% non-resectable local disease and 57% symptomatic metastases. In univariate analysis, pat. without local treatment had a median OS of 14.4m, pts. with local therapy 28.1m (p<0.001). Pts. not receiving local treatment were significantly more likely to have multiorgan or CNS involvement (p< 0.001), symptoms at diagnosis (p=0.009), non-resectable tumor (p<0.001) and were more likely to die within the first 30d after diagnosis (p< 0.001). In multivariate analysis, local treatment had no significant impact on OS. The only significant variables were: number of involved organs, symptoms at diagnosis, receptor status, grading, and size of the local tumor. The effect of local treatment on OS was not homogenous across subgroups. Local treatment was a significant factor in tumors with only one involved organ or asymptomatic disease. In all other groups, local treatment did not result in an OS benefit. Conclusions: Our cohort showed significantly improved OS in univariate analysis if the breast primary tumor had been removed in metastatic disease. Yet, the decision for local treatment was biased by the extent and presentation of metastatic disease. Pts. with more advanced MBC seem not to benefit from removal of the primary tumor. However, we see significant influence in pts. with limited and asymptomatic MBC. The potential dissemination of tumor stem cells from the breast primary in metastatic but locally untreated disease may only influence prognosis in pts. with limited disease.

The impact of KRAS mutation on radioembolization in the treatment of unresectable liver predominant metastatic colorectal cancer.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 664-664
Author(s):  
Michael Schacht ◽  
Douglas M. Coldwell ◽  
Vivek Sharma
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Median Time ◽  
Metastatic Disease ◽  
Disease Burden ◽  
Hepatic Metastases ◽  
Time To Progression ◽  
Kras Status ◽  
Significant Difference ◽  
The Impact

664 Background: Radioembolization with either Yttrium-90 labeled resin or glass microspheres is an FDA approved treatment for hepatic metastases from primary colorectal cancer. Y-90 therapy is used almost exclusively in unresectable liver metastases. However, radioembolization is only an optional part of the treatment process along with first-line, second-line, and salvage chemotherapy. KRAS is a known proto-onco gene that has typically been studied as a negative prognostic factor in the chemotherapeutic treatment of metastatic colorectal cancer (mCRC). KRAS is a known marker for resistance to anti-EGFR antibodies and generally have a poorer prognosis. The aim of this study is to begin to shed light on the impact of KRAS status on the outcome of patients undergoing radioembolization for the treatment of unresectable liver predominant metastatic CRC, regardless of their chemotherapy regimens. Methods: This is a retrospective analysis of 18 subjects treated with radioembolization for liver predominant metastatic CRC. KRAS status and treatment outcomes were followed for each patient up to the study close date of 9/15/13. Statistical analysis was performed using the Mann-Whitney U test. Results: Of the 18 subjects included in the study, 5 were found to have KRAS mutant oncogene. The remaining 13 were found to have the KRAS wildtype. Overall, those subjects with KRAS mutant were found to have a statistically significant difference in median time to progression of intrahepatic metastatic disease burden when compared to KRAS wildtype even when liver-directed therapy was utilized (2.0 vs. 6.4 months). Differences in median time to progression of extrahepatic metastatic disease burden and overall survival were not found to be statistically significant at this time. Conclusions: KRAS mutant patients are exceedingly difficult to treat due to both intrahepatic and extrahepatic disease recurrence/progression.

Diagnostic characteristics of men harboring lethal prostate cancer: A population-based analysis.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 217-217
Author(s):  
John Thomas Helgstrand ◽  
Nina Klemann ◽  
Birgitte Grønkaer Toft ◽  
Ben Vainer ◽  
Klaus Brasso ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Clinical Characteristics ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Tumor Stage ◽  
Distant Metastatic Disease ◽  
Diagnostic Characteristics ◽  
Localized Disease

217 Background: Prostate specific antigen (PSA) based screening increases the number of men diagnosed with early localized prostate cancer (PCa). Further, curatively intended therapies have been demonstrated to reduce PCa mortality in randomized trials. However, controversy exists, and the overall impact on PCa mortality is less clear. Men who eventually die from PCa may constitute a subgroup with either adverse histopathological characteristics and/or clinically advanced disease at diagnosis. However, the clinical characteristics at diagnosis for men who eventually die from PCa are largely unknown. We retrieved clinical characteristics of all men dying from PCa in Denmark in an 18-year period. Methods: All men who died of PCa during the period 1995 to 2013 were identified in the Danish Causes of Death Registry. Age, Gleason score (GS), tumor stage classification, and PSA were retrieved from the Danish Prostate Cancer Registry (DaPCaR). For validation, manual revision of patient charts was performed. Patients were divided into three clinical phenotypes: distant metastatic disease, locally advanced/N+ disease, and localized disease. Patients with localized disease were further grouped according to GS and PSA. Results: A total of 19,487 men died of PCa in the period 1995-2013. In total, 46.7%, 16.8% and 25.1% of men presented with distant metastatic disease, locally advanced/N+ disease or localized disease, respectively. Among men with localized disease, 85.1% had GS ≥ 7 and only 2.1% (0.5% of all men dying from PCa) only, presented with low risk (PSA < 20 and GS ≤ 6) localized disease at the time of diagnosis. Conclusions: The majority of men (63.5%) who died from PCa had either locally advanced/N+ or M+ disease at diagnosis. Among men with localized PCa at diagnosis, the majority of men subsequently dying from PCa had either PSA > 20 ng/ml and/or adverse histopathological characteristics with Gleason score ≥ 7. A total of 94.5% of patients dying from PCa had either metastatic, locally advanced/N+, and/or GS ≥ 7 disease. Patients with localized disease, PSA < 20 ng/ml and GS ≤ 6 amounted for only 0.5% of all patients dying from PCa.

The impact of peri-operative chemotherapy for patients with lymph node-positive urothelial cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 388-388
Author(s):  
Jeenan Kaiser ◽  
Haocheng Li ◽  
Richard M. Lee-Ying ◽  
Daniel Yick Chin Heng ◽  
Nimira S. Alimohamed
Keyword(s):  
Lymph Node ◽  
Surgical Management ◽  
Urothelial Cancer ◽  
Locally Advanced ◽  
Cox Regression Analysis ◽  
Chemotherapy Group ◽  
T Stage ◽  
Group A ◽  
N Stage ◽  
The Impact

388 Background: Patients with locally advanced urothelial cancer with regional lymph node involvement (LN+) have a poor prognosis. Surgical management of these patients is controversial and practice patterns vary. We evaluated the outcomes of patients with LN+ disease treated with pre-operative chemotherapy and cystectomy, cystectomy and post-operative chemotherapy, and chemotherapy alone. Methods: Patients with urothelial cancer with TxN1-3M0 disease treated with chemotherapy in Alberta from 2005 to 2015 were evaluated. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Cox regression analysis was performed to evaluate the impact of age, gender, T stage, and N stage on survival. Results: 184 patients with LN+ disease treated with chemotherapy were evaluable for outcomes; 42 underwent pre-operative chemotherapy (Group A), 92 underwent post-operative chemotherapy (Group B), and 50 received chemotherapy alone (Group C). The median age at diagnosis was 65 years (range 31-89) and most patients (83%) were male. The median follow-up time was 23.2 months. A higher T stage was seen in patients in Group A, while patients in Group C had a higher N stage. The median number of chemotherapy cycles delivered was equal in all arms at 4. Patients in Group A or B had significantly better PFS and OS compared with patients in Group C (Table). When adjusting for age, gender, T stage, and N stage, patients in Group C had significantly lower OS compared with those patients in Group A (HR 1.87, 95% CI 1.09 – 3.18, p=0.02). Conclusions: In this real-world analysis of patients with LN+ urothelial cancer, patient outcomes were improved with surgical resection of disease in combination with pre-operative chemotherapy. After chemotherapy in fit patients with LN+ disease, surgical management is a reasonable consideration. [Table: see text]

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