Predictors of oncological outcomes in T1G3 patients treated with BCG who undergo radical cystectomy.

PURPOSE: To evaluate the oncological impact of postponing radical cystectomy (RC) to allow further conservative therapies prior to progression in a large multicentre retrospective cohort of T1-HG/G3 patients initially treated with BCG. METHODS: According to the time of RC, the population was divided into 3 groups: patients who did not progress to muscle-invasive disease, patients who progressed before radical cystectomy and patients who experienced progression at the time of radical cystectomy. Clinical and pathological outcomes were compared across the three groups. RESULTS: Of 2451 patients, 509 (20.8%) underwent RC. Patients with tumors > 3 cm or with CIS had earlier cystectomies (HR = 1.79, p = 0.001 and HR = 1.53, p = 0.02, respectively). Patients with tumors > 3 cm, multiple tumors or CIS had earlier T3/T4 or N + cystectomies. In patients who progressed, the timing of cystectomy did not affect the risk of T3/T4 or N + disease at RC. Patients with T3/T4 or N + disease at RC had a shorter disease-specific survival (HR = 4.38, p < 0.001), as did patients with CIS at cystectomy (HR = 2.39, p < 0.001). Patients who progressed prior to cystectomy had a shorter disease-specific survival than patients for whom progression was only detected at cystectomy (HR = 0.58, p = 0.024) CONCLUSIONS: Patients treated with RC before experiencing progression to muscle-invasive disease harbor better oncological and survival outcomes compared to those who progressed before RC and to those upstaged at surgery. Tumor size and concomitant CIS at diagnosis are the main predictors of surgical treatment while tumor size, CIS and tumor multiplicity are associated with extravesical disease at surgery.

Recurrence, progression and cancer-specific mortality according to stage at re-TUR in T1G3 bladder cancer patients treated with BCG: not as bad as previously thought.

PURPOSE: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis to adequately stage and treat the patient. Persistent disease after TUR is not uncommon and is why re-TUR is recommended in T1G3 patients. When there is T1 tumor in the re-TUR specimen, very high risks of progression (82%) have been reported. We analyze the risks of recurrence, progression to muscle-invasive disease and cancer-specific mortality (CSM) according to tumor stage at re-TUR in T1G3 patients treated with BCG. METHODS: In our retrospective cohort of 2451 T1G3 patients, 934 patients (38.1%) underwent re-TUR. 667 patients had residual disease (71.4%): Ta in 378 (40.5%), T1 in 289 (30.9%) patients. Times to recurrence, progression and CSM in the three groups were estimated using cumulative incidence functions and compared using the Cox regression model. RESULTS: During a median follow-up of 5.2 years, 512 patients recurred. The recurrence rate was significantly higher in patients with a T1 at re-TUR (P < 0.001). Progression rates differed according to the pathology at re-TUR, 25.3% in T1, 14.6% in Ta and 14.2% in case of no residual tumor (P < 0.001). Similar trends were seen in both patients with and without muscle in the original TUR specimen. CONCLUSIONS: Patients with T1G3 tumors and no residual disease or Ta at re-TUR have better recurrence, progression and CSM rates than previously reported, with a CSM rate of 13.1 and a 25.3% progression rate in re-TUR T1 disease.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. METHODS: Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. RESULTS: Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. CONCLUSIONS: Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Prediction of non-muscle invasive bladder cancer outcomes assessed by innovative multimarker prognostic models.

BACKGROUND: We adapted Bayesian statistical learning strategies to the prognosis field to investigate if genome-wide common SNP improve the prediction ability of clinico-pathological prognosticators and applied it to non-muscle invasive bladder cancer (NMIBC) patients. METHODS: Adapted Bayesian sequential threshold models in combination with LASSO were applied to consider the time-to-event and the censoring nature of data. We studied 822 NMIBC patients followed-up >10 years. The study outcomes were time-to-first-recurrence and time-to-progression. The predictive ability of the models including up to 171,304 SNP and/or 6 clinico-pathological prognosticators was evaluated using AUC-ROC and determination coefficient. RESULTS: Clinico-pathological prognosticators explained a larger proportion of the time-to-first-recurrence (3.1 %) and time-to-progression (5.4 %) phenotypic variances than SNPs (1 and 0.01 %, respectively). Adding SNPs to the clinico-pathological-parameters model slightly improved the prediction of time-to-first-recurrence (up to 4 %). The prediction of time-to-progression using both clinico-pathological prognosticators and SNP did not improve. Heritability (h (2)) of both outcomes was <1 % in NMIBC. CONCLUSIONS: We adapted a Bayesian statistical learning method to deal with a large number of parameters in prognostic studies. Common SNPs showed a limited role in predicting NMIBC outcomes yielding a very low heritability for both outcomes. We report for the first time a heritability estimate for a disease outcome. Our method can be extended to other disease models.

LINE-1 methylation in leukocyte DNA, interaction with phosphatidylethanolamine N-methyltransferase variants and bladder cancer risk.

BACKGROUND: Aberrant global DNA methylation is shown to increase cancer risk. LINE-1 has been proven a measure of global DNA methylation. The objectives of this study were to assess the association between LINE-1 methylation level and bladder cancer risk and to evaluate effect modification by environmental and genetic factors. METHODS: Bisulphite-treated leukocyte DNA from 952 cases and 892 hospital controls was used to measure LINE-1 methylation level at four CpG sites by pyrosequencing. Logistic regression model was fitted to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). Interactions between LINE-1 methylation levels and environmental and genetic factors were assessed. RESULTS: The risk of bladder cancer followed a nonlinear association with LINE-1 methylation. Compared with subjects in the middle tertile, the adjusted OR for subjects in the lower and the higher tertiles were 1.26 (95% CI 0.99-1.60, P=0.06) and 1.33 (95% CI 1.05-1.69, P=0.02), respectively. This association significantly increased among individuals homozygous for the major allele of five single-nucleotide polymorphisms located in the phosphatidylethanolamine N-methyltransferase gene (corrected P-interaction<0.05). CONCLUSIONS: The findings from this large-scale study suggest that both low and high levels of global DNA methylation are associated with the risk of bladder cancer.

Analysis of molecular intra-patient variation and delineation of a prognostic 12-gene signature in non-muscle invasive bladder cancer; technology transfer from microarrays to PCR.

BACKGROUND: Multiple clinical risk factors and genetic profiles have been demonstrated to predict progression of non-muscle invasive bladder cancer; however, no easily clinical applicable gene signature has been developed to predict disease progression independent of disease stage and grade. METHODS: We measured the intra-patient variation of an 88-gene progression signature using 39 metachronous tumours from 17 patients. For delineation of the optimal quantitative reverse transcriptase PCR panel of markers, we used 115 tumour samples from patients in Denmark, Sweden, UK and Spain. RESULTS: Analysis of intra-patient variation of the molecular markers showed 71% similar classification results. A final panel of 12 genes was selected, showing significant correlation with outcome. In multivariate Cox regression analysis, we found that the 12-gene signature was an independent prognostic factor (hazard ratio=7.4 (95% confidence interval: 3.4-15.9), P<0.001) when adjusting for stage, grade and treatment. Independent validation of the 12-gene panel and the determined cut-off values is needed and ongoing. CONCLUSION: Intra-patient marker variation in metachronous tumours is present. Therefore, to increase test sensitivity, it may be necessary to test several metachronous tumours from a patient's disease course. A PCR-based 12-gene signature significantly predicts disease progression in patients with non-muscle invasive bladder cancer.

Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A.

Precision oncology research is challenging outside the contexts of oncogenic addiction and/or targeted therapies. We previously showed that phosphoproteomics is a powerful approach to reveal patient subsets of interest characterized by the activity of a few kinases where the underlying genomics is complex. Here, we conduct a phosphoproteomic screening of samples from HER2-negative female breast cancer receiving neoadjuvant paclitaxel (N = 130), aiming to find candidate biomarkers of paclitaxel sensitivity. Filtering 11 candidate biomarkers through 2 independent patient sets (N = 218) allowed the identification of a subgroup of patients characterized by high levels of CDK4 and filamin-A who had a 90% chance of achieving a pCR in response to paclitaxel. Mechanistically, CDK4 regulates filamin-A transcription, which in turn forms a complex with tubulin and CLIP-170, which elicits increased binding of paclitaxel to microtubules, microtubule acetylation and stabilization, and mitotic catastrophe. Thus, phosphoproteomics allows the identification of explainable factors for predicting response to paclitaxel.

Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.

INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR. MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions. RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001. CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.

Gallbladder disease and pancreatic cancer risk: a multicentric case-control European study.

BACKGROUND AND AIMS: The overall evidence on the association between gallbladder conditions (GBC: gallstones and cholecystectomy) and pancreatic cancer (PC) is inconsistent. To our knowledge, no previous investigations considered the role of tumour characteristics on this association. Thus, we aimed to assess the association between self-reported GBC and PC risk, by focussing on timing to PC diagnosis and tumour features (stage, location, and resection). METHODS: Data derived from a European case-control study conducted between 2009 and 2014 including 1431 PC cases and 1090 controls. We used unconditional logistic regression models to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) adjusted for recognized confounders. RESULTS: Overall, 298 (20.8%) cases and 127 (11.6%) controls reported to have had GBC, corresponding to an OR of 1.70 (95% CI 1.33-2.16). The ORs were 4.84 (95% CI 2.96-7.89) for GBC diagnosed <3 years before PC and 1.06 (95% CI 0.79-1.41) for ≥3 years. The risk was slightly higher for stage I/II (OR = 1.71, 95% CI 1.15-2.55) vs. stage III/IV tumours (OR = 1.23, 95% CI 0.87-1.76); for tumours sited in the head of the pancreas (OR = 1.59, 95% CI 1.13-2.24) vs. tumours located at the body/tail (OR = 1.02, 95% CI 0.62-1.68); and for tumours surgically resected (OR = 1.69, 95% CI 1.14-2.51) vs. non-resected tumours (OR = 1.25, 95% CI 0.88-1.78). The corresponding ORs for GBC diagnosed ≥3 years prior PC were close to unity. CONCLUSION: Our study supports the association between GBC and PC. Given the time-risk pattern observed, however, this relationship may be non-causal and, partly or largely, due to diagnostic attention and/or reverse causation.

The inherited genetic component of sporadic pancreatic adenocarcinoma.

Pancreatic cancer, like many other complex diseases, has genetic and environmental components to its etiology. It is likely that relatively common genetic variants with modest effects on pancreatic cancer risk play an important role in both familial and sporadic forms of the disease, either individually or in interaction with environmental factors. The relatively high frequency of such variants means that they could potentially explain a substantial portion of disease risk. Here we summarize the findings published to date from genetic association studies. In general, very few low-penetrance variants have been identified and those that have require replication in independent studies. Possible gene-environment interactions arising from these studies also require replication. More comprehensive approaches are needed to make progress, including global analyses of biologically sound pathways and genome-wide association studies. Large sample sizes are required to do this appropriately and multi-study consortia make this possible. A number of consortia of pre-existing studies have already been formed, and these will facilitate the identification of further low-penetrance variants and gene-environment interaction. However, these approaches do not substitute for the design of novel, sufficiently powered studies that apply uniform criteria to case selection, the acquisition of environmental exposure information, and to biological sample collection.

Occupation and bladder cancer in a hospital-based case-control study in Spain.

OBJECTIVES: We investigated the association between occupation and bladder cancer in a hospital-based case-control study conducted in Spain. METHODS: 1219 patients with transitional cell carcinoma of the urinary bladder and 1271 controls selected from 18 hospitals in Spain between June 1998 and September 2000 provided detailed information on life-time occupational history, smoking habits, medical history, and other factors. We used unconditional logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for each occupation and industry, adjusting for age, hospital region, smoking duration, and employment in a high-risk occupation for bladder cancer. RESULTS: Statistically significant increased risks were observed among men employed as machine operators in the printing industry (OR 5.4; 95% CI 1.6 to 17.7), among men employed in the transportation equipment industry (OR 1.6; 95% CI 1.1 to 2.6) and among those who had worked for >/=10 years in the electrical/gas/sanitary services (OR 3.9; 95% CI 1.5 to 10.4) and in hotels and other lodgings (OR 3.1; 95% CI 1.3 to 7.3). Men who worked as miscellaneous mechanics and repairers (OR 2.0; 95% CI 1.1 to 3.6) and as supervisors in production occupations (OR 2.1; 95% CI 1.2 to 3.6) also had excess risks for bladder cancer. Male farmers and those who worked in crop and livestock production had decreased risks for bladder cancer. We found no significant associations between occupation or industry and bladder cancer risk among women. CONCLUSIONS: We did not observe excess bladder cancer risk for many of the occupations identified as being a priori at high risk. Examination of more detailed job exposure information should help clarify these associations.

Work in the textile industry in Spain and bladder cancer.

BACKGROUND/OBJECTIVE: Textile manufacturing is a complex industry that has frequently been associated with bladder cancer. However, results have not been consistent. This study investigated the risk of bladder cancer in Spanish textile workers. METHODS: We analysed data from a multicentre hospital-based case-control study carried out in Spain (1998-2001) including 1219 cases of bladder cancer and 1271 controls. Of those, 126 cases and 122 controls reported a history of employment in the textile industry. Lifetime occupational history was obtained using a computer-assisted personal interview. Occupations, locations and materials used in the textile industry were assessed using a detailed questionnaire and expert assessment. RESULTS: Overall, no increased risk of bladder cancer was found for textile workers, including duration of employment analysis. Increased risks were observed for weavers (OR = 1.82, 95% CI 0.95 to 3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working for more than 10 years appeared to be associated with an increased risk for weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62, 95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials. Statistically significant higher risks were also found for specific combinations of occupations or locations with exposure to synthetics and cotton. CONCLUSIONS: There was no overall increased risk for textile workers, but increased risks were found for specific groups of workers. Our findings indicate that observed risks in previous studies may be better evaluated by analysis of materials used or section worked within the industry and occupation.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives.

Background: Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods: Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results: FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions: The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

Cancer epidemiology: study designs and data analysis.

Among the scientific interests of cancer epidemiology is the identification of both environmental and genetic factors associated with cancer development. Observational designs requiring sophisticated methodology are applied to control for potential confounding factors. The enormous biotechnological potential developed in the last two decades has allowed the integration of a plethora of new biomarkers in epidemiological studies to better define the exposure and "neoclassic" outcomes, as well as incorporating genetic susceptibility factors in both classical and new epidemiological designs. The integration of scopes, objectives, data and tools coming from different disciplines also benefits epidemiology, thus evolving into "systems epidemiology". In this manuscript, we review the basic concepts of study designs and data analysis and introduce readers to the more innovative aspects that are now being applied in epidemiological studies.

Assessment of lifetime exposure to trihalomethanes through different routes.

OBJECTIVES: To evaluate lifetime exposure to trihalomethanes (THM) through ingestion, inhalation, and dermal absorption in a hospital based case-control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. METHODS: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person-years of exposure. RESULTS: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mug/l. THM exposure through ingestion was 23.7 mug/day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5-10% were exposed through swimming in pools. CONCLUSION: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route.

Serum anti-p53 antibodies and prognosis of patients with small-cell lung cancer.

BACKGROUND: Some patients with cancer develop antibodies against the p53 tumor suppressor protein. The presence of these antibodies in serum has been associated with the expression of mutant p53 by the tumor and in some studies with a poorer survival. PURPOSE: The goals of this study were to determine the prevalence of anti-p53 antibodies in the serum of patients with newly diagnosed small-cell lung cancer (SCLC) and to assess the clinical relevance of the presence of these antibodies in the serum, particularly their relationship with tumor response to treatment and with patient survival. METHODS: In this prospective study, serum was obtained from 170 patients at the time of diagnosis of SCLC who were to subsequently receive platinum- or doxorubicin-based chemotherapy at any one of four hospitals in Barcelona, Spain, from October 1991 through June 1994. Normal human sera from blood bank donors (n = 50) served as controls. The presence of anti-p53 antibodies was determined by western blot analysis with the use of purified recombinant p53 protein. As of January 1996, 96.5% of the patients had been treated and observed in the study, for a median follow-up time of 33.5 months. Survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression and unconditional logistic regression analyses were conducted. All P values resulted from two-sided tests. RESULTS: Anti-p53 antibodies were detected in the serum of 27 (16%) of the 170 patients studied. None of 50 serum samples from normal individuals contained anti-p53 antibodies. Analysis of pretreatment clinical characteristics demonstrated that a weight loss of less than 5% (P = .025), a serum lactic acid dehydrogenase (LDH) level of less than 450 U/L (P = .002), and limited stage disease (i.e., tumor confined to one hemithorax, with local and regional lymph node positivity for tumor cells and/or ipsilateral pleural effusion allowed) (P < .001) were associated with a statistically significant complete response to therapy. The presence of serum anti-p53 antibodies was not associated with clinical characteristics, such as age (P = .622), functional status (P = 1.0), disease stage (P = .634), complete response to treatment (P = .572), and survival (P = .492) or with any laboratory parameters including known prognostic factors in SCLC, such as serum sodium or LDH concentration (P values of .731 and .246, respectively). CONCLUSIONS AND IMPLICATIONS: The presence of anti-p53 antibodies in the serum of patients with newly diagnosed SCLC was not associated with any clinical characteristics or prognostic markers, suggesting that, in this context, the measurement of anti-p53 antibodies is not a useful prognostic marker.