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Clinical staging in lung cancer has implications for treatment planning and prognosis. We sought to determine the rate of inaccurate clinical stage (relative to pathologic), identify risk factors for inaccuracy, and evaluate the association of inaccuracy on survival. We hypothesized that inaccurate staging was associated with poor survival. In this retrospective cohort study, adult patients who received surgical resection without neoadjuvant treatment for nonsmall cell lung cancer from 2004 to 2020 in the National Cancer Database were categorized by accuracy of clinical stage (relative to pathologic stage). Multivariate models were used to determine risk factors for inaccuracy. The association between inaccuracy and overall survival was also analyzed. We identified 255,598 patients with lung cancer, including 84,543 patients (33.1%) who were inaccurately staged. Stage inaccuracy was associated with higher tumor, node, metastasis stage (T-category 3: odds ratio [OR] = 1.2, 95% confidence interval [CI] 1.15-1.28; N-category 2: OR = 2.6, 95% CI 2.47-2.79), greater quantity of lymph nodes evaluated, and more extensive resection (extended lobectomy/bilobectomy: OR = 1.3, 95% CI 1.20-1.37; pneumonectomy: OR = 1.6, 95% CI 1.54-1.74). Patients undergoing robotic surgery were less likely to be inaccurately staged (OR = 0.89, 95% CI 0.852-0.939). Inaccurate staging was associated with worse overall survival (5-y 67.5% accurate versus 55.4% inaccurate, P < 0.001). Inaccurate staging was also associated with worse survival in a multivariate Cox model (hazard ratio [HR] = 1.3, 95% CI 1.29-1.33). Both "understaging" (path > clinical) and "overstaging" (clinical > path) were associated with inferior survival. Inaccurate clinical stage (relative to pathologic) occurs in one-third of patients receiving surgery for lung cancer. Inaccuracy is associated with poor survival. Quality improvement initiatives should focus on improving clinical staging accuracy. [ABSTRACT FROM AUTHOR]

Renal cell carcinoma (RCC) is occasionally associated with vena cava involvement. Despite recent advances in therapeutic modalities, the 5-year survival in this population continues to be poor. Therefore, further studies are required to better characterize this patient population, especially from the clinicopathologic standpoint. A comprehensive review of patients with RCC and vena cava involvement managed at our institution from 2014 to 2022 was performed. Multiple clinicopathologic parameters including follow-up were obtained. A total of 114 patients were identified. The mean patient age was 63 years (range: 30-84 years). The cohort consisted of 78/114 (68%) males and 36/114 (32%) females. The mean primary tumor size (excluding tumor thrombus) was 11 cm. The majority of tumors (104/114, 91%) were unifocal. Tumor stages were categorized as follows: pT3b (51/114, 44%), pT3c (52/114, 46%), and pT4 (11/114, 10%). Most of the tumors were clear cell RCC 89/114 (78%), although other more aggressive RCC subtypes were also present. Most tumors were WHO/ISUP grade 3 (44/114, 39%) or 4 (67/114, 59%) with sarcomatoid differentiation present in 39/67 (58%). Necrosis was present in 94/114 (82%) tumors. Twenty-three of 114 (20%) tumors were categorized as pM1 and the ipsilateral adrenal gland was the most common site of metastasis. Of the 91 patients categorized as pM, not applicable at nephrectomy, 42/91 (46%) subsequently developed metastasis, most frequently to the lung. Of all patients, only 16/114 (14%) had positive vascular margins and 7/114 (6%) had positive soft tissue margins despite having very advanced disease and a subset considered inoperable at other centers. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to identify the novel microRNAs (miRNAs) for early diagnosis of bladder cancer. Materials and Methods: Differentially expressed miRNAs between early and advanced bladder cancer were identified by differential expression analysis, using miRNA-seq data from The Cancer Genome Atlas (TCGA). The optimal subset of feature miRNAs for pathologic stage prediction was acquired by Random Forest algorithm and was used to construct a support vector machine (SVM) classifier. The performance of the SVM classifier in predicting the progression of bladder cancer samples was validated using an independent validating dataset. An miRNA-regulated target gene network was finally constructed and functional annotation were performed for the target genes. Results: A total of 52 significantly differentially expressed miRNAs were identified between early and advanced bladder cancer samples and 17 of these miRNAs were identified to be feature miRNAs. The 17 feature miRNAs were used to construct an SVM classifier, which showed a high performance in pathologic stage prediction for both training and validating dataset. Besides, our functional annotation analysis showed that the feature miRNAs were significantly involved in biological processes and pathways related to extracellular matrix process and PI3K/Akt signaling. Conclusions: The optimal subset of miRNAs may act as potential therapeutic targets and diagnostic markers of bladder cancer. [ABSTRACT FROM AUTHOR]

Abstract Background The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC. Methods Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model. Results We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases. Conclusions Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC.

Background: Though several nomograms exist, machine learning (ML) approaches might improve prediction of pathologic stage in patients with prostate cancer. To develop ML models to predict pathologic stage that outperform existing nomograms that use readily available clinicopathologic variables., Methods: Patients with prostate adenocarcinoma who underwent surgery were identified in the National Cancer Database. Seven ML models were trained to predict organ-confined (OC) disease, extracapsular extension, seminal vesicle invasion (SVI), and lymph node involvement (LNI). Model performance was measured using area under the curve (AUC) on a holdout testing data set. Clinical utility was evaluated using decision curve analysis (DCA). Performance metrics were confirmed on an external validation data set., Results: The ML-based extreme gradient boosted trees model achieved the best performance with an AUC of 0.744, 0.749, 0.816, 0.811 for the OC, ECE, SVI, and LNI models, respectively. The MSK nomograms achieved an AUC of 0.708, 0.742, 0.806, 0.802 for the OC, ECE, SVI, and LNI models, respectively. These models also performed the best on DCA. Findings were consistent on both a holdout internal validation data set as well as an external validation data set., Conclusions: Our ML models better predicted pathologic stage relative to existing nomograms at predicting pathologic stage. Accurate prediction of pathologic stage can help oncologists and patients determine optimal definitive treatment options for patients with prostate cancer., (© 2024 Wiley Periodicals LLC.)

Aim: This study aimed to investigate the expressions of Nm23-H1 and HER2/neu in Turkish cases of urothelial carcinomas of bladder and to examine their associations with prognostic parameters. Urothelial carcinoma of the bladder is one of the most prevalent cancers worldwide. Nm23-H1 and HER2/neu expressions have been previously studied in urothelial carcinomas. Despite the availability of many reports in the literature, the prognostic significance of these expressions remains unclear. Materials and Methods: Fifty cases of urothelial carcinoma of the bladder treated with radical cystectomy were retrospectively reviewed. The tumor specimens were evaluated by immunohistochemistry using Nm23-H1 and HER2/neu antibodies. Results: Immunohistochemically, Nm23-H1 and HER2/neu expressions were present in 80% and 18% of cases and associated with pathological stage (p=0.025 and p=0.023, respectively). Conclusion: Both antibodies were noted in patients with advanced stage cancer, which can adversely affect prognosis in infiltrative urothelial carcinomas of the bladder. HER2/neu may be a target for therapy. [ABSTRACT FROM AUTHOR]

Background: The clinical pathologic stages (stage I, II, III-IV) of hepatocellular carcinoma (HCC) are closely linked to the clinical prognosis of patients. This study aims at investigating the gene expression and mutational profile in different clinical pathologic stages of HCC.Methods: Based on the TCGA-LIHC cohort, we utilized a series of analytical approaches, such as statistical analysis, random forest, decision tree, principal component analysis (PCA), to identify the differential gene expression and mutational profiles. The expression patterns of several targeting genes were also verified by analyzing the Chinese HLivH060PG02 HCC cohort, several GEO datasets, HPA database, and diethylnitrosamine-induced HCC mouse model.Results: We identified a series of targeting genes with copy number variation, which is statistically associated with gene expression. Non-synonymous mutations mainly existed in some genes (e.g.,TTN, TP53, CTNNB1). Nevertheless, no association between gene mutation frequency and pathologic stage distribution was detected. The random forest and decision tree modeling analysis data showed a group of genes related to different HCC pathologic stages, including GAS2L3 and SEMA3F. Additionally, our PCA data indicated several genes associated with different pathologic stages, including SNRPA and SNRPD2. Compared with adjacent normal tissues, we observed a highly expressed level of GAS2L3, SNRPA, and SNRPD2 (P = 0.002) genes in HCC tissues of our HLivH060PG02 cohort. We also detected the high expression pattern of GAS2L3, SEMA3F, SNRPA, and SNRPD2 in the datasets of GSE102079, GSE76427, GSE64041, GSE121248, GSE84005, and the qPCR assay using diethylnitrosamine-induced HCC mouse model. Moreover, SEMA3F and SNRPD2 protein were highly stained in the HCC tissues of the HPA database. The high expression level of these four genes was associated with the poor survival prognosis of HCC cases.Conclusions: Our study provides evidence regarding the gene expression and mutational profile in different clinical pathologic stages of TCGA HCC cases. Identifying four targeting genes, including GAS2L3, SNRPA, SNRPD2, and SEMA3F, offers insight into the molecular mechanisms associated with different prognoses of HCC. [ABSTRACT FROM AUTHOR]

Background Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear. Patients and methods We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA). Results We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways. Conclusion In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future.

Objectives Rete testis invasion by germ cell tumors is frequently concomitant with lymphovascular or spermatic cord invasion (LVI/SCI); independent implications for staging are uncertain. Methods In total, 171 seminomas and 178 nonseminomatous germ cell tumors (NSGCTs; 46 had 1%-60% seminoma component) came from five institutions. Metastatic status at presentation, as a proxy for severity, was available for all; relapse data were unavailable for 152. Rete direct invasion (ReteD) and rete pagetoid spread (ReteP) were assessed. Results ReteP and ReteD were more frequent in seminoma than NSGCT. In seminoma, tumor size bifurcated at 3 cm or more or less than 3 cm predicted metastatic status. Tumors with ReteP or ReteD did not differ in size from those without invasions but were less than with LVI/SCI; metastatic status or relapse did not show differences. In NSGCT, ReteP/ReteD did not correlate with size, metastatic status, or relapse. Conclusions Findings support retaining American Joint Committee for Cancer pathologic T1 stage designation for rete testis invasion and pT1a/pT1b substaging of seminoma. [ABSTRACT FROM AUTHOR]

Background. To avoid diagnostic errors such as missed diagnosis and errors in staging tumors due to inadequate tissue sampling, pathologists submit additional sections (AS). Objective. This study assessed frequency, diagnostic yield, distribution, and cost of AS. Method. Among 1542 AS cases, we calculated mean AS per case; fraction of AS that altered diagnosis or stage; AS variation by tissue, malignant versus benign lesions, presence or absence of neoadjuvant therapy, mass, margin, lymph nodes, or other source, resident versus pathologist assistant (PA) dissector; and AS cost per case. Results. Overall 9.2 ± 8.8 AS were collected per case. In only 3.8% (58/1542) of cases AS altered diagnosis or stage. Urinary bladder cases provoked the most AS: 19.5 ± 15.1 per case. Significantly more AS came from malignant versus benign lesions (10.8 ± 9.7 vs 7.6 ± 7.5, P = <.0001) and from specimens treated with neoadjuvant therapy versus malignant lesions not so treated (12.3 ± 9.4 vs 10.3 ± 9.8, P = .02). Lymph nodes were sampled more heavily compared with mass, margin, and other sites combined (11.8 ± 11.4 vs 8.9 ± 8.4, P = .003), but in 78.4% (1209/1542) of cases, AS were from mass. Of diagnosis or stage altering AS cases, two thirds (38/58) were from masses, one fifth (11/58) from lymph nodes, a 10th (6/58) from margins, and a 20th (3/58) from other specimen sites. Resident versus pathologist assistant dissection caused no significant AS difference. AS contributed 40% cost per case. Conclusions. AS per case ranged widely; their diagnostic yield was low; they were highest in urinary bladder specimens, in malignant and particularly neoadjuvant-treated lesions. Although lymph nodes were most heavily sampled, most AS were from masses. Resident dissection did not increase AS and cost of AS was high. [ABSTRACT FROM AUTHOR]

Abstract: Background: Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Methods: Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. Results: There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Conclusion: Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. [ABSTRACT FROM AUTHOR]

Objective To determine the frequency, associated factors, and prognosis of clinicopathologic stage discrepancy in oropharyngeal squamous cell carcinoma (OPSCC). Study Design Retrospective study using a national database. Setting National Cancer Database. Subjects and Methods Cases of OPSCC diagnosed between January 1, 2004, and December 31, 2013, with full clinical and pathologic staging information available were identified. Demographic, clinicopathologic, and treatment variables associated with overall stage discrepancy were identified by multivariate logistic regression analysis. Results In total, 7731 cases of OPSCC were identified. Overall stage discrepancy was present in 30.2% of cases (21.9% upstaging, 8.2% downstaging). A total of 13.1% of cases were T-upstaged, and 10.5% of cases were T-downstaged; 22.9% of cases were N-upstaged, and 8.6% of cases were N-downstaged. Upstaging by overall stage was associated with a high Charlson-Deyo score, high tumor grade, number of lymph nodes examined, and increasing tumor size. No factors were positively associated with downstaging. High tumor grade was negatively associated with downstaging. For stage II, III, and IVA tumors, upstaging was associated with poorer OS. Conclusion Clinicopathologic stage discrepancy is common in OPSCC and is likely attributable to insensitive clinical staging techniques as well as to intrinsic tumor biologic properties. Upstaging is associated with poorer prognosis, which is likely due to advancement of disease. [ABSTRACT FROM AUTHOR]

Testicular cancer is the most common solid neoplasm of adult men between the ages of 20 and 40 years. Germ cell tumors account for 95% of all testicular tumors. The assessment of staging is essential to guide further management of patients with testicular cancer and to prognosticate cancer-related outcomes. Postradical orchiectomy treatment options, including adjuvant therapy and active surveillance, vary based on the anatomical extent of disease, serum tumor markers, pathologic diagnosis, and imaging. This review provides an update on the germ cell tumor staging system adopted by the 8th edition of the American Joint Commission on Cancer (AJCC) Staging Manual, treatment implications, risk factors, and predictors of outcomes., (Published by Elsevier Inc.)

Background: The role of prophylactic cranial irradiation (PCI) on small cell lung cancer (SCLC) has been established based on the two-stage system of limited versus extensive disease and the treatment modality of chemoradiotherapy. However, the use of PCI after combined-modality treatment with surgery for resectable limited-stage SCLC has not been investigated sufficiently. We conducted a retrospective study to evaluate risk factors for brain metastasis (BM) in patients with surgically resected SCLC to identify those most likely to benefit from PCI. Patients and methods: The records of 126 patients with completely resected SCLC and definitive TNM stage based on histological examination between 2003 and 2009 were reviewed. The cumulative incidence of BM was estimated using the Kaplan–Meier method and differences between the groups were analyzed using the log-rank test. Multivariate Cox regression analysis was applied to assess the risk factors of BM. Results: Twenty-eight patients (22.2%) developed BM at some point during their clinical course. The actuarial risk of developing BM at 3 years was 9.7% in patients with p-stage I disease, 18.5% in patients with p-stage II disease, and 35.4% in patients with p-stage III disease (p = 0.013). The actuarial risk of developing BM at 3 years in patients with LVI was 39.9% compared to 17.5% in patients without LVI (p = 0.003). Multivariate analysis identified pathologic stage (hazard ratio [HR] = 2.013, p = 0.017) and LVI (HR = 1.924, p = 0.039) as independent factors related to increased risk of developing BM. Conclusion: Patients with completely resected p-stage II-III SCLC and LVI are at the highest risk for BM. [ABSTRACT FROM AUTHOR]

Testicular cancer is the most common solid neoplasm of adult men between the ages of 20 and 40 years. Germ cell tumors account for 95% of all testicular tumors. The assessment of staging is essential to guide further management of patients with testicular cancer and to prognosticate cancer-related outcomes. Postradical orchiectomy treatment options, including adjuvant therapy and active surveillance, vary based on the anatomical extent of disease, serum tumor markers, pathologic diagnosis, and imaging. This review provides an update on the germ cell tumor staging system adopted by the 8th edition of the American Joint Commission on Cancer (AJCC) Staging Manual, treatment implications, risk factors, and predictors of outcomes., (Published by Elsevier Inc.)

Copyright of Archivos de Bronconeumología (English Edition) is the property of Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Archivos de Bronconeumología (English Edition) is the property of Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: A PSA velocity (PSAV) >0.35 ng/ml/year approximately 10-15 years prior to diagnosis is associated with a greater risk of lethal prostate cancer. Some have recommended that a PSAV >0.35 ng/ml/year should prompt a prostate biopsy in men with a low serum PSA (<4 ng/ml) and benign DRE. However, less is known about the utility of this PSAV cutpoint for the prediction of treatment outcomes among men undergoing radical prostatectomy (RP). Methods: Between 1992 and 2007, 339 men underwent RP at our institution with a preoperative PSA <4 ng/ml, benign DRE, and multiple preoperative PSA measurements. PSAV was calculated by linear regression analysis using all PSA values within 18 months prior to diagnosis. Kaplan-Meier survival analysis was performed, and biochemical progression rates were compared between PSAV strata using the log-rank test. Results: The preoperative PSAV was >0.35 ng/ml/year in 124 (36.6%) of 339 men. Although there were no significant differences in clinico-pathological characteristics based upon PSAV, men with a PSAV >0.35 ng/ml/year were significantly more likely to experience biochemical progression after RP at a median follow-up of 4 years ( P = 0.022). Conclusions: In this low-risk population with a preoperative PSA <4 ng/ml and benign DRE, approximately 1/3 had a preoperative PSAV >0.35 ng/ml/year. Physicians should carefully monitor men with a preoperative PSA >0.35 ng/ml/year as they are at increased risk of biochemical progression following RP. [ABSTRACT FROM AUTHOR]

Abstract: Context: In the last few years, the treatment of renal cell carcinoma (RCC) has progressed significantly, and some histopathologic issues have become important for selection and follow-up after medical and surgical therapies. Objective: The aim of this collaborative article is to review the most recent literature on the role of traditional histopathologic features obtained from renal core biopsy or nephrectomy specimens in the management of confined, locally advanced, and metastatic RCC. Evidence acquisition: A nonsystematic review of the literature was performed in April 2010 using the Medline database. Multiple free-text searches were performed for the following items: renal cell carcinoma, clear cell, papillary, chromophobe, histologic* subtype*, histotype*, nuclear grade*, necrosis, sarcomatoid differentiation, biopsy, molecular marker*, and cytogenetic marker*. A total of 2369 records were retrieved from Medline, and 263 full-text studies were considered and partially included in the present review. A panel of experts reached consensus on the main subheadings of this paper. Evidence synthesis: Core needle biopsies can provide important information that is useful to avoid the overtreatment of benign tumors and to help plan watchful waiting or minimally invasive treatments in selected patients. Tumor histotype is fundamental in the pathologic report. In the context of integrated prognostic systems, the combination of the most important clinical and pathologic factors (TNM stage, Fuhrman nuclear grade, presence of necrosis, microvascular invasion, and sarcomatoid dedifferentiation) allows us to reach a high prognostic accuracy. These models can be used to select patients suitable for adjuvant protocols, to design an appropriate follow-up schedule, and to provide careful patient counseling. Molecular and cytogenetic markers should be further evaluated. Conclusions: The histopathologic definition of parenchymal epithelial renal tumors is fundamental to plan the management and follow-up of patients with locally confined, locally advanced, and metastatic RCC. [Copyright &y& Elsevier]

OBJECTIVE To evaluate the subclassifications of pT2 diseases in tumour-nodes-metastases (TNM) staging system for prostate cancer. PATIENTS AND METHODS We retrospectively analysed the data of 372 patients who underwent radical retropubic prostatectomy (RRP) for pathologically organ-confined prostate cancer at our institution. Pathological staging of all subjects were re-evaluated using the 1997 and the 2002 TNM staging system for prostate cancer. Various clinicopathological features along with biochemical recurrence-free survival (BRFS) of pT2 subgroups were assessed. RESULTS Using the 2002 TNM staging criteria, 87 of the tumours (23.4%) were pT2a, and 284 (76.3%) were pT2c. Of all subjects, there was only one (0.3%) pathological 2002 T2b tumour identified. When subjects were classified according to the 1997 versions of the T2 subclassification (pT2a vs pT2b), the 1997 pT2a and pT2b cases showed no significant difference regarding BRFS (log-rank P = 0.645) among those who were followed-up for >2 years after RRP. Also, pathological stage (1997 pT2a vs pT2b) was not a significant predictor of BRFS in either uni- or multivariate analysis ( P = 0.289 and P = 0.241, respectively). Only preoperative serum PSA level and pathological Gleason score along with positive surgical margin were significant predictors of PSA outcome after RRP on multivariate analysis. CONCLUSION Our results suggest that two- or three-tiered subclassification of pT2 organ-confined prostate cancer via methods used in the previous or current TNM staging system may not be appropriate. Efforts should be made to upgrade the current TNM staging system for prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer.Methods and Materials: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage).Results: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation.Conclusions: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the prostate-specific antigen (PSA) levels and PSA velocity (PSAV) in a group of men who were diagnosed with prostate cancer and who were enrolled in a prostate cancer screening trial. PSA levels and PSAV were examined as risk factors for an elevated biopsy Gleason score. The study also examined whether PSAV and/or PSA level in patients who underwent prostatectomy, when combined with clinical predictors had better predictive ability for advanced pathologic stage compared with clinical predictors alone.

Background: Caveolin-1, as a major component of caveolae, is involved in the regulation of cell cycle by impacting various signaling pathways. Previous studies of caveolin-1 in cancer showed two contrary results. In most in vitro studies, caveolin-1 played a role as a tumor suppressor. On the other hand, the elevated expression of caveolin-1 was often reported to be associated with poor clinical outcome in human studies. These results indicate differential biological functions of caveolin-1 depending on the development and progression stage of cancer in vivo. Methods: To clarify the correlation between the clinicopathologic profiles of pulmonary squamous cell carcinomas and the expression of caveolin-1, 107 cases of formalin-fixed and paraffin-embedded tissues of pulmonary squamous cell carcinomas were immunohistochemically evaluated for the expression of caveolin-1 by the tissue-array method. Results: Caveolin-1 was expressed in 34 cases (31.7%) among 107 cases of pulmonary squamous cell carcinoma. The expression of caveolin-1 was statistically correlated with pathologic stage (stage I and II vs. III; P<0.001), pT (T1 and T2 vs. T3 and T4; P=0.001), and pN (N1 vs. N2 and N3; P=0.0143). The patients with caveolin-1 expression in pulmonary squamous cell carcinomas showed a poorer prognosis than those in caveolin-1-negative group (P=0.0345). Conclusion: The expression of caveolin-1 is significantly correlated with advanced pathologic stage and poor prognosis in pulmonary squamous cell carcinoma. The results of current study suggest that the expression level of caveolin-1 may be a candidate factor for predicting prognosis in patients with pulmonary squamous cell carcinoma. [Copyright &y& Elsevier]

Purpose: The patients diagnosed with colorectal cancer (CRC) are likely to undergo differential outcomes in clinical survival owing to different pathologic stages. However, signatures in association with pathologic evolution and CRC prognosis are not clearly defined. This study aimed to identify pathologic evolution-related genes in CRC based on both single-cell and bulk transcriptomics. Patients and methods: The CRC single-cell transcriptomic dataset (GSE81861, n=590) with clinical information and tumor microenvironmental tissues was collected to identify the pathologic evolution-related genes. The colonic adenocarcinoma and rectum adenocarcinoma transcriptomics from The Cancer Genome Atlas were obtained as the training dataset (n=363) and 5 other CRC transcriptomics cohorts from Gene Expression Omnibus (n=1031) were acquired as validation data. Graph-based clustering analysis algorithm was applied to identify pathologic evolution-related cell populations. Pseudotime analysis was performed to construct the trajectory plot of pathologic evolution and to define hub genes in the evolution process. Cell-type identification by estimating relative subsets of RNA transcripts was then executed to build a novel cell infiltration classifier. The prediction efficacy of this classifier was validated in bulk transcriptomic datasets. Results: Epithelial and T cells were elucidated to be related to the pathologic stages in CRC tissues. Pseudotime analysis and survival analysis indicated that HOXC5, HOXC8 and BMP5 were the marker genes in pathologic evolution process. Our cell infiltration classifier exhibited excellent forecast efficacy in predicting pathologic stages and prognosis of CRC patients. Conclusion: We identified pathologic evolution-related genes in single-cell transcriptomic and proposed a novel specific cell infiltration classifier to forecast the prognosis of CRC patients based on pathologic stage-related hub genes HOXC6, HOXC8 and BMP5., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Oral squamous cell carcinoma (OSCC) is a major lethal malignant cancer of the head and neck region, yet its molecular mechanisms of tumourigenesis are still unclear., Patients and Methods: We performed weighted gene co-expression network analysis (WGCNA) on RNA-sequencing data with clinical information obtained from The Cancer Genome Atlas (TCGA) database. The relationship between co-expression modules and clinical traits was investigated by Pearson correlation analysis. Furthermore, the prognostic value and expression level of the hub genes of these modules were validated based on data from the TCGA database and other independent datasets from the Gene Expression Omnibus (GEO) database and the Human Protein Atlas database. The significant modules and hub genes were also assessed by functional analysis and gene set enrichment analysis (GSEA)., Results: We found that the turquoise module was strongly correlated with pathologic T stage and significantly enriched in critical functions and pathways related to tumourigenesis. PPP1R12B, CFD, CRYAB, FAM189A2 and ANGPTL1 were identified and statistically validated as hub genes in the turquoise module and were closely implicated in the prognosis of OSCC. GSEA indicated that five hub genes were significantly involved in many well-known cancer-related biological functions and signaling pathways., Conclusion: In brief, we systematically discovered a co-expressed turquoise module and five hub genes associated with the pathologic T stage for the first time, which provided further insight that WGCNA may reveal the molecular regulatory mechanism involved in the carcinogenesis and progression of OSCC. In addition, the five hub genes may be considered candidate prognostic biomarkers and potential therapeutic targets for the precise early diagnosis, clinical treatment and prognosis of OSCC in the future., Competing Interests: The authors declare there are no competing interests., (©2020 Hu et al.)

Background: In the Surveillance, Epidemiology, and End Results population-based data, the survival curves reversed between T4N0 (stages IIB or IIC) and T1-2N1 (stage IIIA) in rectal cancer. However, T4N0 had a higher stage than T1-2N1 in the current colorectal staging system., Patients and Methods: We analyzed 1804 patients with rectal cancer who were treated with preoperative chemoradiotherapy and curative surgery. We grouped patients by pathologic stage, and recurrence-free survival (RFS) and overall survival rates were calculated and compared for each stage. We evaluated prognostic factors that influenced recurrence and survival., Results: In the recurrence and survival analysis, 3-year RFS rates were 95.9% for ypStage 0, 94.0% for ypStage I, 78.9% for ypStage IIA, 55.8% for ypStage IIB/C, 80.2% for ypStage IIIA, 64.6% for ypStage IIIB, and 44.9% for ypStage IIIC. Patients with ypStage IIB/C showed significantly worse RFS (P = .004) than did those with ypStage IIIA. The ypStage IIB/C group showed significantly higher rates of both locoregional recurrence (24.3% vs. 5.5%; P = .02) and distant metastasis (31.6% vs. 17.1%; P = .048) than did the ypStage IIIA group. Compared with ypStage IIIA, ypStage IIB/C showed significantly higher pre-chemoradiotherapy carcinoembryonic antigen (P = .004), circumferential radial margin involvement (P = .001), and positive perineural invasion (P = .014)., Conclusion: Patients with rectal cancer staged ypT4N0 were associated with higher locoregional recurrence and distant metastasis rates than those staged ypT1-2N1 in the current staging system., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Our objective is to explore the accuracy of magnetic resonance imaging in determining the preoperative T and N staging, pathological stage, and the length of esophageal tumor in patients with esophageal cancer., Methods: This retrospective analysis included 57 patients admitted to the Department of Thoracic Surgery of The First Affiliated Hospital of Nanjing Medical University between January 2015 and December 2016. Postoperative pathological results were used as the reference to verify the accuracy of magnetic resonance imaging in evaluating tumor T and N staging, pathological stage, and tumor length. The correlation between tumor lengths-measured using magnetic resonance imaging and the surgical specimen measurements-was evaluated., Results: The mean age of the patients was 64.6 ± 7.2 years, with a range of 47 to 77 years. The overall accuracy rate of magnetic resonance imaging in T staging of esophageal cancer was 63.2%; magnetic resonance imaging was generally consistent in the N staging of esophageal cancer. Magnetic resonance imaging and surgical evaluation of tumor length were in excellent agreement (κ = .82, P < .001), while that of gastroscopy and postoperative pathology was moderate (κ = .63, P < .001)., Conclusion: Magnetic resonance imaging is highly accurate in determining the preoperative T and N staging, pathologic stage, and tumor length in patients with esophageal cancer, which is important in deciding the choice of preoperative treatment and the surgical approach.

Purpose: To determine the accuracy of 18 F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG-PET/CT) scans in assessing the response to neoadjuvant chemotherapy (NAC) in patients with bladder cancer scheduled to undergo radical cystectomy (RC)., Patients and Methods: All patients treated at our center for muscle-invasive bladder cancer (MIBC) were counseled and offered NAC before RC. FDG-PET/CT scans were performed before the initiation of chemotherapy and after completion of the regimen. Patients with disease with complete response to NAC were those who had (pT0) or residual carcinoma-in-situ (pTis) on final pathology. Those who were downstaged from MIBC to non-MIBC were considered to have a chemosensitive tumor. We used percentage reduction in standardized maximum uptake value (SUV max ) from PET/CT scans as our measure to correlate with the final pathology after cystectomy., Results: Thirty-seven patients with MIBC who underwent NAC followed by RC were included in the final analysis. FDG-PET/CT had 75% sensitivity (89.66% specificity) in identifying those with complete pathologic response with a 100% change in SUV max , and 83% sensitivity (94% specificity) for the detection of chemosensitive tumors., Conclusion: FDG-PET/CT can help determine the response of primary tumor to NAC in patients with MIBC and thus can more accurately predict the prognosis of the patients, or potentially the appropriate time for cystectomy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The 8th edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects survival of clinically and pathologically staged patients, requiring separate groupings for each cell type, but ypTNM groupings are identical for both cell types. Clinical categories, typically obtained by imaging with minimal histologic information, are limited by resolution of each method. Strengths and shortcomings of clinical staging methods should be recognized. Complementary cytology or histopathology findings may augment imaging and aid initial treatment decision-making. However, prognostication using clinical stage groups remains coarse and inaccurate compared with pTNM. Pathologic staging is losing its relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains relevant for early-stage cancers and as a staging and survival reference point. Although pathologic stage could facilitate decision-making, its use to direct postoperative adjuvant therapy awaits more effective treatment. Prognostication using pathologic stage groups is the most refined of all classifications. Postneoadjuvant staging (ypTNM) is introduced by the AJCC but not adopted by the Union for International Cancer Control (UICC). Drivers of this addition include absence of equivalent pathologic (pTNM) categories for categories peculiar to the postneoadjuvant state (ypT0N0-3M0 and ypTisN0-3M0), dissimilar stage group compositions, and markedly different survival profiles. Thus, prognostication is specific for patients undergoing neoadjuvant therapy. The role of ypTNM classification in additional treatment decision-making is currently limited. Precision cancer care advances are necessary for this information to be clinically useful., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.