Cancer-specific Survival Hazard Ratio Research Articles

Efficacy of cytoreductive surgery for metastatic upper tract urothelial carcinoma: a Surveillance, Epidemiology and End Results (SEER) study of 508 patients.

Cisplatin-based combination chemotherapy alone is currently considered the standard of care for patients with metastatic upper tract urothelial carcinoma (mUTUC). However, less research has been done on the efficacy of other combinations. In this study, we explored the role of cytoreductive surgery in patients with mUTUC receiving different types of systemic therapy. Data from 9,436 anonymized records were abstracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2008-2018. Of these, 508 individuals received systemic therapy subsequent to being diagnosed with mUTUC. These patients had all been treated with systemic therapies such as chemotherapy and/or radiotherapy. Patients were stratified into either a non-surgical or surgical group based on cytoreductive surgery status before systemic therapeutics commenced. Kaplan-Meier curves were used to compare overall survival (OS) and cancer-specific survival (CSS). Cox's proportional hazard models were then used to analyze prognostic factors related to OS and CSS. Of the 508 cases, 36.8% (n=187) had received cytoreductive surgery with systemic treatments. The remaining 63.2% (n=321) received either chemotherapy and/or radiotherapy alone. Kaplan-Meier curves showed that 11.6% had 3-year OS [95% confidential interval (CI): 7.1-17.3] for cytoreductive surgery with systemic treatment and 4.9% (95% CI: 2.7-8.0) for systemic treatment alone (P=0.001). The 3-year CSS was 14.9% for cytoreductive surgery plus systemic treatment (95% CI: 9.4-21.7%) and 6.0% (95% CI: 3.4-9.8%) for systemic treatments alone (P=0.003). Under multivariate regression analysis, primary ureter site OS had a hazard ratio (HR) of 0.74 (95% CI: 0.58-0.95, P=0.02) and a CSS HR of 0.72 (95% CI: 0.56-0.94, P=0.01). The cytoreductive surgery OS HR was 0.79 (95% CI: 0.65-0.95, P=0.02) and the CSS HR was 0.75 (95% CI: 0.61-0.92, P=0.006). Additionally, chemotherapy had an OS HR of 0.46 (95% CI: 0.33-0.0.65, P<0.001) and a CSS HR of 0.44 (95% CI: 0.31-0.63, P<0.001). Bones and liver metastases were also indicative of poorer prognosis. Validation was conducted through subgroup analysis which suggested cytoreductive surgery was effective only for patients who received chemotherapy or combined chemo-radiotherapy but not for radiotherapy alone. Cytoreductive surgery provided significantly increased OS and CSS for mUTUC patients who received chemotherapy or combined chemo-radiotherapy in this study. In addition, the primary tumor and metastatic sites were shown to be related to improved patient survival although this was a small and relatively homogeneous cohort of study, sample therefore, further research is required.

Pathologic and survival outcomes following radical cystectomy for “progressive” and “de novo” muscle-invasive bladder cancer: A meta-analysis stratified by neoadjuvant chemotherapy status

ObjectiveTo compare survival and pathologic outcomes in patients with progressive muscle-invasive bladder cancer (pgMIBC) and de novo muscle-invasive bladder cancer (dnMIBC) after radical cystectomy (RC), with a focus on the role of neoadjuvant chemotherapy (NAC). MethodsA comprehensive literature search was conducted on PubMed and EMBASE databases to identify studies comparing pgMIBC to dnMIBC. Survival outcomes, including cancer-specific survival (CSS), overall survival (OS), and recurrence-free survival (RFS), and pathologic outcomes (rates of ≤pT1, pT0, pT3/T4, and pN+ disease) were compared between pgMIBC and dnMIBC. ResultsThe analysis included 19 cohorts from 16 studies, categorized into 3 groups based on NAC use: 1. patients who underwent RC and were all treated with NAC (RC + NAC only group); 2. patients who underwent RC, with or without NAC (RC +/- NAC group); 3. patients who only underwent RC without NAC (RC only group). Compared to dnMIBC, pgMIBC demonstrated worse outcomes for CSS, OS, and RFS. In the RC + NAC only group (3 cohorts), the hazard ratio (HR) for CSS was 1.52 (95% confidence interval [CI] = 1.05–2.2), while the HR for OS was 1.46 (95%CI = 1.05–2.02). Similarly, in the RC +/- NAC group (6 cohorts for CSS and 3 cohorts for OS), the HR for CSS was 1.27 (95%CI = 1.05–1.55), and the HR for OS was 1.27 (95%CI = 1.08–1.51). There were no significant differences observed in pathologic outcomes, including rates of ≤pT1, pT0, and pT3/T4 disease, across all subgroups. However, pgMIBC was associated with a higher risk of nodal metastatic (pN+) disease in the RC + NAC only group (4 cohorts, relative risk [RR] = 1.43, 95%CI = 1.12–1.84). ConclusionsThe findings highlight the potentially worse prognosis in patients with pgMIBC compared to dnMIBC, even with the modern use of NAC. The study emphasizes the importance of careful patient counseling, further classification of patients for treatment selection, and the consideration of additional or innovative systemic therapies for pgMIBC.

Clinical significance of preoperative CALLY index for prognostication in patients with esophageal squamous cell carcinoma undergoing surgery

The C-reactive protein-albumin-lymphocyte (CALLY) index has been identified as a useful and sensitive predictive tool for stratification in cancers. This investigation aimed to validate the prognostic ability of CALLY in esophageal squamous cell carcinoma (ESCC). Clinical characteristics of 318 patients with ESCC who underwent radical excision were gathered and analyzed retrospectively. A restricted cubic spline (RCS) model was used to determine an ideal threshold of CALLY due to the non-linear relation. To investigate the predictors, Cox hazard regression analysis was used. The recursive partitioning analysis (RPA), a method of risk categorization, was also developed for prognostic prediction. The receiver operating characteristic (ROC) curves and decision curve analysis (DCA) curves were used to distinguish from the traditional TNM stage. Patients were compared by groups according to the optimal threshold of CALLY index, which was depicted by the non-linear relation between the cancer-specific survival (CSS) and CALLY index (P < 0.0001). Compared to those with high CALLY index, patients with low CALLY index experienced significantly worse 5-year CSS (21.8% vs. 62.6%, P < 0.001). At different TNM stages, patients with high CALLY index also had better 5-year CSS (I: P = 0.029; II: P < 0.001; III: P < 0.001) in subgroup analyses. The hazard ratio for CSS was 0.368 and CALLY index was an independent predictive factor (P < 0.001). Using TNM stage and CALLY-based RPA algorithms, a new staging was created. The RPA model considerably outperformed the TNM classification for prognostication using ROC (P < 0.001). The DCA also demonstrated that the new model outperformed the TNM stage with significantly improved accuracy for CSS. The prognostic value of CALLY in ESCC undergoing radical resection was initially determined in this study. CALLY was substantially related to prognosis and might be utilized in conjunction with TNM to evaluate ESCC prior to surgery.

D3 lymph node dissection improves the survival outcome in patients with pT2 colorectal cancer.

The extent of lymphadenectomy in patients with pT2 colorectal cancer (CRC) remains controversial. This study aimed to elucidate the effects of D3 and D2 lymph node dissection (LND) on survival in patients diagnosed with pT2 CRC. This was a retrospective cohort study from a high-volume cancer center in Japan. From April 2007 to December 2020, 6273 patients with primary CRC were included in the study; among these, 616 patients diagnosed with pT2 CRC underwent radical colorectal resection. Propensity score matching (PSM) was applied to balance potential confounding factors, and a total of 104 matched pairs were extracted from the entire cohort. Independent risk factors associated with prognosis were determined by Cox regression analysis. The main outcome measures were overall survival (OS) and cancer-specific survival (CSS). Before PSM, there was a statistically significant difference across the cohort in OS and CSS (p = 0.000 and 0.013) between D3 and D2 LND groups; the estimated hazard ratio (HR) was 2.2 (95% confidence interval (CI), 1.1-4.4, p = 0.031) for OS in the D3 LND and 4.4 (95% CI, 1.7 to 11, p = 0.0027) for CSS (p = 0.013). There was also a significant difference (p = 0.024) in OS between the D3 and D2 LND groups in the matched cohort, with an estimated HR for OS of 3.3 (95% CI, 1.2 to 9.1, p = 0.024) and an estimated HR for CSS of 7.2 (95% CI, 1.6 to 33, p = 0.011). D3 LND had a significant survival advantage in the treatment of pT2 CRC. The results of this study provide a theoretical basis for the application of D3 LND in radical surgery for preoperative T2 CRC.

Survival benefits and disparities in radiation therapy for elderly patients with pancreatic ductal adenocarcinoma.

Older patients represent a unique subgroup of the cancer patient population, for which the role of cancer therapy requires special consideration. However, the outcomes of radiation therapy (RT) in elderly patients with pancreatic ductal adenocarcinoma (PDAC) are not well-defined in the literature. To explore the use and effectiveness of RT in the treatment of elderly patients with PDAC in clinical practice. Data from patients with PDAC aged ≥ 65 years between 2004 and 2018 were collected from the Surveillance, Epidemiology, and End Results database. Multivariate logistic regression analysis was performed to determine factors associated with RT administration. Overall survival (OS) and cancer-specific survival (CSS) were evaluated using the Kaplan-Meier method with the log-rank test. Univariate and multivariate analyses with the Cox proportional hazards model were used to identify prognostic factors for OS. Propensity score matching (PSM) was applied to balance the baseline characteristics between the RT and non-RT groups. Subgroup analyses were performed based on clinical characteristics. A total of 12245 patients met the inclusion criteria, of whom 2551 (20.8%) were treated with RT and 9694 (79.2%) were not. The odds of receiving RT increased with younger age, diagnosis in an earlier period, primary site in the head, localized disease, greater tumor size, and receiving chemotherapy (all P < 0.05). Before PSM, the RT group had better outcomes than did the non-RT group [median OS, 14.0 vs 6.0 mo; hazard ratio (HR) for OS: 0.862, 95% confidence interval (CI): 0.819-0.908, P < 0.001; and HR for CSS: 0.867, 95%CI: 0.823-0.914, P < 0.001]. After PSM, the survival benefit associated with RT remained comparable (median OS: 14.0 vs 11.0 mo; HR for OS: 0.818, 95%CI: 0.768-0.872, P < 0.001; and HR for CSS: 0.816, 95%CI: 0.765-0.871, P < 0.001). Subgroup analysis revealed that the survival benefits (OS and CSS) of RT were more significant in patients aged 65 to 80 years, in regional and distant stages, with no surgery, and receiving chemotherapy. RT improved the outcome of elderly patients with PDAC, particularly those aged 65 to 80 years, in regional and distant stages, with no surgery, and who received chemotherapy. Further prospective studies are warranted to validate our results.

Association between time to diagnosis, time to treatment, and ovarian cancer survival in the United States

ObjectiveEvaluate the association between time to diagnosis and treatment of advanced ovarian cancer with overall and ovarian cancer specific mortality using a retrospective cross sectional study of a population based...

P119 - Treatment patterns, outcomes, and costs associated with localized upper tract urothelial carcinoma

Background Upper tract urothelial carcinoma (UTUC) is a heterogeneous disease that presents a clinical management challenge for the urologic surgeon. We assessed treatment patterns, costs, and survival outcomes among patients with nonmetastatic UTUC. Methods We identified 4114 patients diagnosed with nonmetastatic UTUC from 2004 to 2013 in the Survival Epidemiology, and End Results-Medicare population-based database. Patients were stratified into low- or high-risk disease groups. Median total costs from 30 days prior to diagnosis through 365 days after diagnosis were compared between groups. Overall and cancer-specific survival were evaluated using Cox proportional hazards regression. All statistical tests were 2-sided. Results After risk stratification, 1027 (24.9%) and 3087 (75.0%) patients were classified into low- vs high-risk UTUC groups. Most patients underwent at least 1 surgical intervention (95.1%); 68.4% underwent at least 1 endoscopic intervention. Patients diagnosed with high- vs low-risk UTUC were more likely to undergo nephroureterectomy (83.6% vs 72.0%; P < .001); few patients with low-risk disease were exclusively managed endoscopically (16.9%). At 365 days after diagnosis, costs of care for high- vs low-risk UTUC were statistically significantly higher ($108 520 vs $91 233; median difference $16 704, 95% confidence interval [CI] = $11 619 to $21 778; P < .001). Those with high-risk UTUC had worse cancer-specific and overall survival compared with patients with low-risk UTUC (cancer-specific survival hazard ratio [HR] = 4.14, 95% CI = 3.19 to 5.37; overall survival HR = 1.78, 95% CI = 1.62 to 1.96). Conclusions UTUC continues to be managed primarily with nephroureterectomy, regardless of risk stratification, and patients with high-risk UTUC have worse overall and cancer-specific survival. Substantial costs are associated with management of low- and high-risk UTUC, with the latter being more costly up to 1 year from diagnosis.

Treatment Patterns, Outcomes, and Costs Associated With Localized Upper Tract Urothelial Carcinoma.

BackgroundUpper tract urothelial carcinoma (UTUC) is a heterogeneous disease that presents a clinical management challenge for the urologic surgeon. We assessed treatment patterns, costs, and survival outcomes among patients with nonmetastatic UTUC.MethodsWe identified 4114 patients diagnosed with nonmetastatic UTUC from 2004 to 2013 in the Survival Epidemiology, and End Results–Medicare population-based database. Patients were stratified into low- or high-risk disease groups. Median total costs from 30 days prior to diagnosis through 365 days after diagnosis were compared between groups. Overall and cancer-specific survival were evaluated using Cox proportional hazards regression. All statistical tests were 2-sided.ResultsAfter risk stratification, 1027 (24.9%) and 3087 (75.0%) patients were classified into low- vs high-risk UTUC groups. Most patients underwent at least 1 surgical intervention (95.1%); 68.4% underwent at least 1 endoscopic intervention. Patients diagnosed with high- vs low-risk UTUC were more likely to undergo nephroureterectomy (83.6% vs 72.0%; P < .001); few patients with low-risk disease were exclusively managed endoscopically (16.9%). At 365 days after diagnosis, costs of care for high- vs low-risk UTUC were statistically significantly higher ($108 520 vs $91 233; median difference $16 704, 95% confidence interval [CI] = $11 619 to $21 778; P < .001). Those with high-risk UTUC had worse cancer-specific and overall survival compared with patients with low-risk UTUC (cancer-specific survival hazard ratio [HR] = 4.14, 95% CI = 3.19 to 5.37; overall survival HR = 1.78, 95% CI = 1.62 to 1.96).ConclusionsUTUC continues to be managed primarily with nephroureterectomy, regardless of risk stratification, and patients with high-risk UTUC have worse overall and cancer-specific survival. Substantial costs are associated with management of low- and high-risk UTUC, with the latter being more costly up to 1 year from diagnosis.

Impact of Metformin Use on Survival in Patients with Gastric Cancer and Diabetes Mellitus Following Gastrectomy.

Studies have shown the anticancer effects of metformin in vitro. However, whether metformin can prevent cancer recurrence or prolong survival in patients with gastric cancer (GC) and diabetes mellitus (DM) post-gastrectomy remains unknown. We evaluated the beneficial effects of metformin in patients with GC and DM post-gastrectomy. We recruited 2400 patients with GC (1749 without DM, 651 with DM) who underwent surgery between 1997 and 2010. Patients with DM were stratified into metformin (group 1) and non-metformin (group 2) users. Their clinicopathological data were recorded prospectively, and demographics, recurrence-free survival (RFS), and cancer-specific survival (CSS) were compared. Tumour recurrence risk and cause of death were analysed between groups 1 and 2 among patients with DM stratified by tumour stage. We also compared RFS and overall survival among patients with and without DM. Tumour recurrence occurred in 201 patients with GC: 57 (25%) in group 1 and 144 (37%) in group 2. After adjusting for confounders, metformin significantly prolonged CSS (hazard ratio (HR) = 0.54, 95% confidence interval (CI) = 0.38–0.77) in patients with stage I–III GC and DM. In subgroup analysis, metformin users with stage III GC and DM had significantly prolonged CSS compared to non-metformin users (HR = 0.45, 95% CI = 0.30–0.68), with an insignificant difference in patients with stage I–II GC. Adjusted HRs for RFS and CSS were significantly lower in patients with stage I–III GC and DM than those in patients without DM (0.67 (95% CI = 0.54–0.92) and 0.62 (95% CI = 0.50–0.77), respectively), with an insignificant difference in patients with stage I GC. Metformin significantly reduces tumour recurrence risk and improves CSS in patients with stage III GC and DM post-gastrectomy. Further prospective studies may confirm the efficacy of metformin as an adjunctive treatment for advanced GC postoperatively.

Pulmonary Metastasectomy for Colorectal Cancer: Predictors of Survival in Routine Surgical Practice

Resection of lung metastases is considered standard treatment for patients with metastatic colorectal cancer. We describe surgical management, prognostic factors, and outcomes in routine clinical practice. All cases of colorectal cancer lung metastases in Ontario, Canada, resected during 2002 to 2009 were identified using the Ontario Cancer Registry and linked electronic records. Pathology reports were reviewed to identify extent of disease. The study population included 420 patients (60% male). Median age was 64 years. A solitary metastasis was present in 61% (256 of 420). Mean size of the largest metastasis was 2.4 cm. Lymph nodes were resected in 63% (263 of 420) of patients. The 5-year cancer-specific survival (CSS) and overall survival (OS) was 42% (95% confidence interval [CI], 37% to 47%) and 40% (95% CI, 35% to 45%), respectively. On adjusted analyses, greater number (p < 0.001) and size (p= 0.001) of lesions and lymph node involvement (p < 0.001) were associated with inferior CSS and OS. Lymph node positivity was strongly associated with survival (adjusted CSS hazard ratio, 2.19 [95% CI, 1.48 to 3.25]; adjusted OS hazard ratio, 2.08 [95% CI, 1.41 to 3.07]). Unadjusted 5-year CSS/OS was 49%/47% for node-negative disease and 19%/19% for node-positive disease. The negative prognostic effect of size (>2 cm) and number (>1) of lesions was additive: 5-year CSS/OS ranged from 57%/55% (single lesion <2 cm) to 24%/20% (multiple lesions, largest lesion>2 cm). Long-term survival of patients with resected colorectal cancer lung metastases in routine practice is comparable to outcomes reported in institutional case series. Lymph node positivity is strongly associated with reduced survival. Combining size and number of metastatic lesions in advance of the operation may facilitate treatment decision making.

Radiotherapy for Patients With Resected Tumor Deposit-Positive Colorectal Cancer: A Surveillance, Epidemiology, and End Results-Based Population Study.

- According to the American Joint Committee on Cancer's Cancer Staging Manual, 7th edition, TNM classification, tumor deposit (TD)-positive colorectal cancers (CRCs) are classified as N1c. The effects of radiotherapy and the effects of the updated American Joint Committee on Cancer 7th edition TNM N1c classification for patients with TD-positive CRC are unclear. - To investigate outcomes of radiotherapy in patients with resected TD-positive CRC. - Resected TD-positive CRCs diagnosed from 2010 to 2014 were identified in the Surveillance, Epidemiology, and End Results 18 database. Factors associated with overall survival (OS) and cancer-specific survival (CSS) were investigated using Kaplan-Meier and Cox proportional hazards models. - We included 2712 qualified CRC patients, who either underwent adjuvant radiotherapy (n = 187; 6.9%) or received no radiotherapy (n = 2525; 93.1%). Univariate Cox proportional models showed improved CSS among all CRC patients who underwent adjuvant radiotherapy (CSS hazard ratio, 0.73; 95% CI, 0.57-0.95) and among rectal cancer patients when separated by location (hazard ratio, 0.57; 95% CI, 0.40-0.83), although these associations were attenuated in multivariable-adjusted models. There was improved OS among rectal cancer patients (hazard ratio, 0.77; 95% CI, 0.59-0.99). In subgroup analyses, radiotherapy was not associated with OS or CSS in either metastatic or nonmetastatic CRC patients. Instead, N1c category (versus N0) was associated with a worse OS (hazard ratio, 1.43; 95% CI, 1.31-1.57) but was not associated with CSS. - Radiotherapy did not independently improve OS among TD-positive CRC patients. In this study, classifying TD positivity as N1c was associated with worse OS than classifying TD positivity as N0. The findings seem to challenge the benefits of radiotherapy and the new N1c classification of TD for TD-positive CRC patients.

Population-based study to re-evaluate optimal lymph node yield in colonic cancer.

It is well established that lymph node (LN) yield in colonic cancer resection has prognostic significance, although optimal numbers are not clear. Here, LN thresholds associated with both LN positivity and survival were evaluated in a single population-based data set. Treatment records were linked to the Ontario Cancer Registry to identify a 25 per cent random sample of all patients with stage II/III colonic cancer between 2002 and 2008. Multivariable regression and Cox models evaluated factors associated with LN positivity and cancer-specific survival (CSS) respectively. Optimal thresholds were obtained using sequential regression analysis. On adjusted analysis of 5508 eligible patients, younger age (P < 0·001), left-sided tumours (P = 0·003), higher T category (P < 0·001) and greater LN yield (relative risk 0·89, 95 per cent c.i. 0·81 to 0·97; P = 0·007) were associated with a greater likelihood of LN positivity. Regression analyses with multiple thresholds suggested no substantial increase in LN positivity beyond 12-14 LNs. Cox analysis of stage II disease showed that lower LN yield was associated with a significant increase in the risk of death from cancer (CSS hazard ratio range 1·55-1·74; P < 0·001) compared with a greater LN yield, with no significant survival benefit beyond a yield of 20 LNs. Similarly, for stage III disease, a lower LN yield was associated with an increase in the risk of death from cancer (CSS hazard ratio range 1·49-2·20; P < 0·001) versus a large LN yield. In stage III disease, there was no observed LN threshold for survival benefit in the data set. There is incongruity in the optimal LN evaluation for colonic cancer. Although the historically stated threshold of 12 LNs may ensure accurate staging in colonic cancer, thresholds for optimal survival are associated with far greater yields.

Evaluation of Preoperative Aspartate Transaminase/Alanine Transaminase Ratio as an Independent Predictive Biomarker in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy: APropensity Score Matching Study.

The usefulness of the aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) as a predictive biomarker for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN) remains unclear. The data from 118 patients were retrospectively evaluated. The endpoints were cancer-specific survival (CSS) and overall survival (OS) after CN. We compared these according to the AST/ALT ratio before and after 1:1 propensity score matching. The independent predictors for CSS and OS were also analyzed. The area under the receiver operating characteristic curve was 0.603. The maximum Youden index indicated that the cutoff value for the AST/ALT ratio was 1.24. Before matching, a high AST/ALT ratio was significantly associated with inferior CSS and OS (P< .05 for all). After matching, 34 patients each were allocated to the high and low AST/ALT ratio groups. In the matched cohort, CSS and OS tended to be lower in the high AST/ALT ratio group, although the results were not statistically significant (median CSS, 18.4 months vs. not reached, P=.121; OS, 18.4 months vs. not reached, P= .0957). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an independent predictor for CSS and OS (CSS hazard ratio, 2.17, P= .0472; OS hazard ratio, 2.30, P=.0258). The preoperative AST/ALT ratio can be an effective predictive biomarker for CSS and OS in patients with mRCC.

Screening Uptake Differences Are Not Implicated in Poorer Breast Cancer Outcomes among Singaporean Malay Women.

PurposeThis study was undertaken to examine the impact of screening and race on breast cancer outcomes in Singapore.MethodsAn institutional database was reviewed, and invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) data were analyzed separately. Overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS) were assessed.ResultsThe study included 6,180 IDC and 1,031 DCIS patients. The median follow-up time was 4.1 years. Among IDC patients, Malay women were the youngest when first diagnosed, and were more likely to present with advanced stage disease. Malay women also had the highest proportion of T3 and T4 tumors at 14.2%, compared with Chinese women at 8.7% and Indian women at 9.6% (p<0.001). Malay women had a higher incidence of node-positive disease at 58.3% compared with Chinese women at 46.4% and Indian women at 54.9% (p<0.001). Malay subjects also had higher-grade tumors; 61.8% had grade 3 tumors compared with 45.8% of Chinese women and 52% of Indian women (p<0.001). Furthermore, tumors in Malay subjects were less endocrine-sensitive and more human epidermal growth factor receptor 2 enriched. Malay women had the lowest 5- and 10-year OS, DFS, and CSS rates (p<0.001). After separating clinically and screen-detected tumors, multivariate analysis showed that race was still significant for outcomes. For screen-detected tumors, the OS hazard ratio (HR) for Malay women compared to Chinese women was 5.78 (95% confidence interval [CI], 2.64–12.64), the DFS HR was 2.18 (95% CI, 1.19–3.99), and the CSS HR was 5.93 (95% CI, 2.15–16.39). For DCIS, there were no statistically significant differences in the tumor size, grade, histology subtypes, or hormone sensitivity.ConclusionMalay race is a poor prognostic factor in both clinically and screen-detected IDC. Special attention should be given to the detection and follow-up of breast cancer in this group.

Metformin as an adjuvant treatment for cancer: a systematic review and meta-analysis

Metformin use has been associated with a reduced risk of developing cancer and an improvement in overall cancer survival rates in meta-analyses, but, to date, evidence to support the use of metformin as an adjuvant therapy in individual cancer types has not been presented. We systematically searched research databases, conference abstracts and trial registries for any studies reporting cancer outcomes for individual tumour types in metformin users compared with non-users, and extracted data on patients with early-stage cancer. Studies were assessed for design and quality, and a meta-analysis was conducted to quantify the adjuvant effect of metformin on recurrence-free survival (RFS), overall survival (OS) and cancer-specific survival (CSS), to inform future trial design. Of 7670 articles screened, 27 eligible studies were identified comprising 24 178 participants, all enrolled in observational studies. In those with early-stage colorectal cancer, metformin use was associated with a significant benefit in all outcomes [RFS hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.47-0.85; OS HR 0.69, CI 0.58-0.83; CSS HR 0.58, CI 0.39-0.86]. For men with early-stage prostate cancer, metformin was associated with significant, or borderline significant, benefits in all outcomes (RFS HR 0.83, CI 0.69-1.00; OS HR 0.82, CI 0.73-0.93; CSS HR 0.58, CI 0.37-0.93); however, there was significant heterogeneity between studies. The data suggest that prostate cancer patients treated with radical radiotherapy may benefit more from metformin (RFS HR 0.45, CI 0.29-0.70). In breast and urothelial cancer, no significant benefits were identified. Sufficient data were not available to conduct analyses on the impact of metformin dose and duration. Our findings suggest that metformin could be a useful adjuvant agent, with the greatest benefits seen in colorectal and prostate cancer, particularly in those receiving radical radiotherapy, and randomised, controlled trials which investigate dose and duration, alongside efficacy, are advocated.

High Ki-67 Immunohistochemical Reactivity Correlates With Poor Prognosis in Bladder Carcinoma: A Comprehensive Meta-Analysis with 13,053 Patients Involved.

Ki-67 is considered as one of prime biomarkers to reflect cell proliferation and immunohistochemical Ki-67 staining has been widely applied in clinical pathology. To solve the widespread controversy whether Ki-67 reactivity significantly predicts clinical prognosis of bladder carcinoma (BC), we performed a comprehensive meta-analysis by combining results from different literature.A comprehensive search was conducted in the Chinese databases of WanFang, China National Knowledge Infrastructure and Chinese VIP as well as English databases of PubMed, ISI web of science, EMBASE, Science Direct, and Wiley online library. Independent studies linking Ki-67 to cancer-specific survival (CSS), disease-free survival (DFS), overall survival (OS), progression-free survival (PFS), and recurrence-free survival (RFS) were included in our meta-analysis. With the cut-off values literature provided, hazard ratio (HR) values between the survival distributions were extracted and later combined with STATA 12.0.In total, 76 studies (n = 13,053 patients) were eligible for the meta-analysis. It was indicated in either univariate or multivariate analysis for survival that high Ki-67 reactivity significantly predicted poor prognosis. In the univariate analysis, the combined HR for CSS, DFS, OS, PFS, and RFS were 2.588 (95% confidence interval [CI]: 1.623–4.127, P < 0.001), 2.697 (95%CI: 1.874–3.883, P < 0.001), 2.649 (95%CI: 1.632–4.300, P < 0.001), 3.506 (95%CI: 2.231–5.508, P < 0.001), and 1.792 (95%CI: 1.409–2.279, P < 0.001), respectively. The pooled HR of multivariate analysis for CSS, DFS, OS, PFS, and RFS were 1.868 (95%CI: 1.343–2.597, P < 0.001), 2.626 (95%CI: 2.089–3.301, P < 0.001), 1.104 (95%CI: 1.008–1.209, P = 0.032), 1.518 (95%CI: 1.299–1.773, P < 0.001), and 1.294 (95%CI: 1.203–1.392, P < 0.001), respectively. Subgroup analysis of univariate analysis by origin showed that Ki-67 reactivity significantly correlated with all 5 clinical outcome in Asian and European-American patients (P < 0.05). For multivariate analysis, however, the pooled results were only significant for DFS, OS, and RFS in Asian patients, for CSS, DFS, PFS, and RFS in European-American patients (P < 0.05). In the subgroup with low cut-off value (<20%), our meta-analysis indicated that high Ki-67 reactivity was significantly correlated with worsened CSS, DFS, OS, PFS, and RFS on univariate analysis (P < 0.05). For multivariate analysis, the meta-analysis of literature with low cut-off value (<20%) demonstrated that high Ki-67 reactivity predicted shorter DFS, PFS, and RFS in BC patients (P < 0.05). In the subgroup analysis of high cut-off value (≥20%), our meta-analysis indicated that high Ki-67 reactivity, in either univariate or multivariate analysis, significantly correlated with all five clinical outcomes in BC patients (P < 0.05).The meta-analysis indicates that high Ki-67 reactivity significantly correlates with deteriorated clinical outcomes in BC patients and that Ki-67 can be considered as an independent indicator for the prognosis by the meta-analyses of multivariate analysis.

The Modified Glasgow Prognostic Score and Survival in Colorectal Cancer: A Pooled Analysis of the Literature.

It has been reported that the combination of inflammation parameters, such as albumin and C-reactive protein, in the modified Glasgow prognostic score (m-GPS) is a poor prognostic indicator in several malignancies. Here, we quantify the prognostic impact of this score and assess its value in colorectal cancer. A systematic review of electronic databases was conducted to identify publications exploring the association of m-GPS with outcome in colorectal cancer. Overall survival (OS) was the primary outcome, and cancer-specific survival (CSS), progression-free survival, and disease-free survival were secondary outcomes. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) were included in a metaanalysis. Pooled HRs were computed and weighted using generic inverse-variance and random effects modeling. All statistical tests were two-sided. Nine studies, which included a total of 2,227 patients, were included in the analysis. Overall, according to multivariate analysis, m-GPS≥1 was independently associated with an HR for OS of 1.69 (95% CI=1.4-2.04; P<0.00001), an effect observed in all stages of disease. Six studies including a total of 1,751 patients reported HR for CSS. Overall, a high m-GPS was associated with an HR for CSS of 1.84 (95% CI=1.43-2.37; P<0.00001). A high m-GPS is associated with poor OS in colorectal cancer. The m-GPS is a cheap and easily evaluable biomarker, and its incorporation into known prognostic scores for clinical decision making warrants further investigation in this setting.

Delivery of perioperative chemotherapy for bladder cancer in routine clinical practice.

Few articles have documented regimens and timing of perioperative chemotherapy for bladder cancer in routine practice. Here, we describe practice patterns in the general population of Ontario, Canada. In this retrospective cohort study, treatment and physician billing records were linked to the Ontario Cancer Registry to describe use of neoadjuvant (NACT) and adjuvant (ACT) chemotherapy among all patients with muscle-invasive bladder cancer treated with cystectomy in Ontario 1994-2008. Time to initiation of ACT (TTAC) was measured from cystectomy. Multivariate Cox regression was used to identify factors associated with overall (OS) and cancer-specific survival (CSS). Of 2944 patients undergoing cystectomy, 4% (129/2944) and 19% (571/2944) were treated with NACT and ACT, respectively. Five-year OS was 25% [95% confidence interval (CI) 17% to 34%] for NACT, 29% (95% CI 25% to 33%) for ACT cases. Among patients with identifiable drug regimens, cisplatin was used in 82% (253/308) and carboplatin in 14% (43/308). The most common regimens were gemcitabine-cisplatin (54%, 166/308) and methotrexate, vinblastine, doxorubicin, cisplatin (MVAC) (21%, 66/308). Mean TTAC was 10 weeks; 23% of patients had TTAC >12 weeks. TTAC >12 weeks was associated with inferior OS [hazard ratio (HR) 1.28, 95% CI 1.00-1.62] and CSS (HR 1.30, 95% CI 1.00-1.69). In adjusted analyses, OS and CSS were lower among patients treated with carboplatin compared with those treated with cisplatin; OS HR 2.14 (95% CI 1.40-3.29) and CSS HR 2.06 (95% CI 1.26-3.37). Most patients in the general population receive cisplatin, and this may be associated with superior outcomes to carboplatin. Initiation of ACT beyond 12 weeks is associated with inferior survival. Patients should start ACT as soon as they are medically fit to do so.

Prognostic Significance of Mucinous Differentiation of Endometrioid Adenocarcinoma of the Endometrium

Using Surveillance, Epidemiology, and End Results database we identified 43,882 (97.0%) women with endometrioid adenocarcinomas and 1,374 (3.0%) with mucinous adenocarcinomas. Women with mucinous tumors were older (P < .0001), more often white (P = .04), and more often to present at advanced stage (P = .001). Survival was similar for both histologies; the hazard ratio for cancer-specific survival for mucinous compared to endometrioid tumors was 0.90 (95% CI, 0.74–1.09) while the hazard ratio for overall survival was 0.95 (95% CI, 0.85–1.07). Five-year survival for stage I mucinous tumors was 89.9% (95% CI, 87.6–91.9%) compared to 89.0% (95% CI, 88.6–89.4%) for endometrioid tumors.

336 IS A FATAL FAMILY HISTORY OR THE APPARENT MODE OF DISEASE TRANSMISSION OF PROSTATE CANCER A PROGNOSTIC FACTOR FOR SURVIVAL?

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History (II)1 Apr 2013336 IS A FATAL FAMILY HISTORY OR THE APPARENT MODE OF DISEASE TRANSMISSION OF PROSTATE CANCER A PROGNOSTIC FACTOR FOR SURVIVAL? Kathleen Herkommer, Elsa Donel, Juergen Gschwend, and Martina Kron Kathleen HerkommerKathleen Herkommer Munich, Germany More articles by this author , Elsa DonelElsa Donel Munich, Germany More articles by this author , Juergen GschwendJuergen Gschwend Munich, Germany More articles by this author , and Martina KronMartina Kron Ulm, Germany More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1722AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Little is known about familial clustering of fatal prostate cancer (pc) and an association between fatal family history (FH), apparent mode of disease transmission and survival. The aim of this study was to determine the impact of a fatal FH and the apparent mode of disease transmission on survival of prostate cancer patients after radical prostatectomy in Germany. METHODS 2883 patients after radical prostatectomy with at least one first-degree relative with pc of the nationwide database familial pc in Germany were stratified according to (1) family history (fatal vs. nonfatal) and (2) apparent mode of disease transmission (male to male vs. non male to male). Fatal FH was defined as patients who had at least one first-degree relative and/or one second-degree relative who died of pc. Biochemical progression free survival (BPFS), overall survival (OS) and cancer specific survival (CSS) for each epidemiological feature were analyzed according to the method of Kaplan and Meier and subgroups were compared in a proportional hazard regression calculating hazard ratio (HR) and p-value. RESULTS In the subgroup with fatal pc we observed less organ confined tumors (60.6% vs. 67.1%), higher rates of male to male transmission (66.9% vs. 54.4%), more hereditary patients (53.2% vs. 18.6%), more patients with more than 2 affected relatives (67.3% vs. 25.9%) and an earlier age of onset (median age of diagnosis 62.5 yr vs. 63.6 yr). Survival was comparable in the fatal subgroup and the nonfatal subgroup: BPFS HR=0.96 (p=0.695), OS HR=1.13 (p=0.506), CSS HR=0.92 (p=0.788). In the subgroup with male to male transmission we observed more patients with a fatal FH (13.9% vs. 8.7%), more patients with more than 2 affected relatives (38.6% vs 23.3%), an earlier age of onset (median age of diagnosis 63.0 yr vs 64.0 yr) and more hereditary patients (30.7% vs. 15.7%). Survival was comparable in the male to male subgroup and the non male to male subgroup: BPFS HR=1.02 (p=0.736), OS HR=0.94 (p=0.681), CSS HR=0.88 (p=0.561). CONCLUSIONS Survival was not remarkably different in familial patients with fatal family history compared to those with non-fatal FH as well as in patients with male to male vs. non male to male transmission. Our findings suggest that fatal FH and the apparent mode of disease transmission are not associated with poorer survival and worse clinical outcome. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e136 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathleen Herkommer Munich, Germany More articles by this author Elsa Donel Munich, Germany More articles by this author Juergen Gschwend Munich, Germany More articles by this author Martina Kron Ulm, Germany More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...