American Joint Committee On Cancer Staging System Research Articles

Negative Prognostic Implication of TERT Promoter Mutations in Human Papillomavirus\u2013Negative Tonsillar Squamous Cell Carcinoma Under the New 8th AJCC Staging System

Telomerase reverse transcriptase gene promoter (TERTp) mutation is a potential candidate for pathogenesis and therapeutic target of tonsillar squamous cell carcinomas (TSCCs) in association with human papillomavirus (HPV). Their clinical relevance has not been validated under the new 8th American Joint Committee on Cancer (AJCC) staging system. We analyzed real-time peptide nucleic acid–mediated PCR and sequencing methods (TERTp mutation) and real-time PCR-based assay (HPV) in 80 surgically resected TSCCs. The 8th edition staging system improved the stratification of the early and advanced stages and between T or N categories for overall survival over the 7th edition. TERTp mutation was found in 7.5%, and HPV in 80.0% of the patients. The majority (83.3%) of TERTp mutation cases were HPV-positive TSCCs. Applying the 8th edition staging system, TERTp mutation was an independent factor of poor prognosis for disease-free survival (DFS) in TSCC patients, supporting the clinical significance of TERTp mutation in tonsil cancer. TERTp mutations were also negatively correlated with overall survival and DFS in HPV-negative TSCCs. Conclusively, TERTp mutation provides negative prognostic impact on survival of surgically managed tonsil cancers staged with the AJCC 8th edition.

Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection

BackgroundBoth the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear.Methods178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.ResultsThere was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31 months (P = 0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0 IU/L) and CA19–9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.ConclusionThe newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.

Staging of T2 and T3 nasopharyngeal carcinoma: Proposed modifications for improving the current AJCC staging system.

ObjectivesWe aimed to reconstitute T2 and T3 stage classification in nasopharyngeal carcinoma (NPC) cases and verify its utility in clinical settings.Materials and MethodsWe enrolled 792 NPC patients. Cox proportional hazards model was used to compare the effect sizes (hazard ratio [HR]) of the cranial structure invasion on survival and select the structures for up‐staging or downstaging T2 and T3 NPC. The samples were reclassified and the survival curves for T2 and T3 stages were analyzed. The proposed new staging system was validated on an external sample (n = 433).ResultsThirteen cranial structures were examined. American Joint Committee on Cancer (AJCC) T3 stage patients with the invasion of the base of the sphenoid (HR = 2.58, 95% CI = 1.16‐5.77) or base of the pterygoid (HR = 2.00, 95% CI = 0.84‐4.77) had significantly lower hazard ratios than T2 stage patients with the invasion of soft tissues in the bilateral parapharyngeal space (HR = 5.26, 95% CI = 2.02‐13.68) and single/bilateral carotid sheath (HR = 7.78, 95% CI = 3.06‐19.76). T3 stage with the invasion of the above‐mentioned bones was reclassified as T2, and T2 stage with the invasion of the above‐mentioned soft‐tissue structures was reclassified as T3. Survival analysis showed a significant difference between the reclassified T2 and T3 stages (P < 0.001). The results were replicated in the validation samples.ConclusionThe proposed staging system for defining T2 and T3 stage NPC appears to be superior to the AJCC 8th edition. It could improve prognosis and optimize the treatment selection.

The American Joint Committee on Cancer staging for metastatic head and neck cutaneous squamous cell carcinoma: A multi-institutional study of within-stage heterogeneity and impact on prognostic performance.

The American Joint Committee on Cancer (AJCC) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) stratifies risk poorly. We hypothesized that this results from prognostic heterogeneity within N and TNM groups. Retrospective analysis of disease-specific survival (DSS) in a multicenter study of 1146 patients with nodal metastases from HNcSCC. The majority of patients were classified as pN2a or pN3b (83.1%) and TNM stage IV (90.6%). On multivariate analysis, there was statistically significant prognostic heterogeneity within these groups based on the number and size of nodal metastases, immunosuppression, and perineural invasion. When stage IV patients were categorized into low, moderate, and high-risk groups based on adverse features, there was wide variation in prognosis with 5-year DSS ranging from 90% to 60% (P < .001). The AJCC staging system stratifies risk poorly in HNcSCC due to significant prognostic heterogeneity within pN2a, pN3b, and stage IV groups.

Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification

BackgroundSeminoma accounts for 30–50% of testicular germ cell tumors (TGCT)—the most common solid malignancy in men aged 15–35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification’s potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions.MethodsAll consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed.ResultsSeminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P < 0.0001 and P = 0.023, respectively), known adverse biological features.ConclusionsIn our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.

Differences in 7th and 8th edition American Joint Committee on Cancer staging for periocular sebaceous carcinoma

ObjectiveTo examine the clinicopathological features of periocular sebaceous carcinoma and describe the differences in T category between the seventh and eighth editions of the American Joint Committee on Cancer (AJCC) staging system for eyelid carcinoma in a Canadian population. MethodsThis study is a single-centre retrospective review of consecutive patients diagnosed with periocular sebaceous carcinoma at Vancouver General Hospital over a 24-year period. Medical records and pathological slides were reviewed. Clinicopathological features, management, and outcomes were recorded. Each carcinoma was staged as per both the seventh and eighth editions AJCC staging system for eyelid carcinoma. ResultsForty-five patients (25 women, 20 men) were identified with a median age of 74 years (range 42–91 years). Tumour size was with a median of 4 mm (range 1–30 mm) and a mean of 6.7 mm. Using the seventh edition, patients were assigned the following T categories: Tis = 10, T1 = 9, T2 = 11, T3 = 8, T4 = 0. Under the eighth edition, 18 of 45 patients (40%) were restaged, with the majority of these (15 patients, 33%) being downstaged. The eighth edition categories were as follows: Tis = 10, T1 = 22, T2 = 3, T3 = 0, T4 = 3. Three patients developed disease recurrence, 2 of whom (staged T2c and T4b) died of disease. ConclusionsThere were substantial differences in the seventh and eighth editions of AJCC for the staging of periocular sebaceous carcinoma. Our series had small tumours at presentation with infrequent recurrences or metastases. We found a high number of patients with in-situ-only disease.

The Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival after radical cystectomy: external validation in a large bi-institutional cohort.

To perform an external validation of the Cancer of the Bladder Risk Assessment (COBRA) score for estimating cancer-specific survival (CSS) after radical cystectomy (RC) in a large bi-institutional cohort of patients. Patients treated with RC and lymph node dissection (LND) between May 1996 and July 2017 were retrieved from the RC databases of Leuven and Turin. Collected variables were age at RC, tumour stage, lymph node (LN) density, neoadjuvant chemotherapy, the extent of LND, and nodal stage. The primary outcome was CSS visualised using Kaplan-Meier plots. Cox proportional hazard models were used to assess the impact of variables on CSS. We performed a pairwise comparison between the COBRA score levels using a log-rank test corrected by Bonferroni, and developed a simplified COBRA score with three risk categories. To compare models, we assessed concordance indices (C-indices), receiver operating characteristic curves with area under the curve (AUC), calibration plots, and decision curve analysis (DCA). Finally, we compared both COBRA and simplified COBRA models with the established American Joint Committee on Cancer (AJCC) model. A total of 812 patients were included. All COBRA score variables had a significant impact on CSS in a Cox proportional hazard model. However, pairwise comparison of the COBRA subscores could not differentiate significantly between all COBRA score levels. Based on these findings, we developed a simplified COBRA score by introducing three categories within the following COBRA score ranges: low- (0-1) vs intermediate- (2-4) vs high-risk (5-7). A pairwise comparison could discriminate significantly between all COBRA risk categories. When finally comparing COBRA and simplified COBRA models with the AJCC model, AJCC performed better than both. C-indices, AUCs, calibration plots and DCA for AJCC were all better compared with the original and simplified COBRA models. We performed an external validation of the COBRA score in a large bi-institutional cohort. We observed that several risk groups had overlapping CSS, demonstrating suboptimal performance of the COBRA score. Therefore, we constructed a simplified model with three COBRA score risk categories. This model resulted in demarcated risk groups with non-overlapping CSS and good predictive accuracy. However, both COBRA score models were outperformed by the AJCC staging system. Therefore, we conclude that the AJCC staging system should remain the current standard for stratifying patients after RC for CSS.

A Proposed Staging System for Improved Prognostication of MDM2-amplified Liposarcoma.

Despite the release of anatomic site-specific staging systems for soft tissue sarcomas in the eighth edition of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual, the algorithms for sarcomas arising in the extremities/trunk and retroperitoneum differ only in the staging of lymph node metastasis. The retroperitoneum not only provides a larger potential space for tumor growth before the clinical presentation, but its anatomic complexities complicate surgical resection and adversely affect disease-free survival. Here, we propose a new staging system for MDM2-amplified liposarcomas (well-differentiated and dedifferentiated subtypes) that properly emphasizes retroperitoneal localization, degree of differentiation (histologic subtype), and presence of distant metastasis. A retrospective cohort of 4146 adult patients with surgically resected liposarcoma was extracted from the SEER database to compare the natural history of MDM2-amplified liposarcomas arising in the extremities/trunk or retroperitoneum. Separate training and validation datasets were created, and Cox proportional hazard regression, multivariable nonlinear regression, and nomographic analyses determined the most significant parameters in predicting sarcoma-specific death. A new staging system was derived and its predictive accuracy was compared with the AJCC, eighth edition system using areas under receiver operating characteristic curves and multiple concordance indices. Multivariable analysis showed that dedifferentiation (hazard ratio [HR]=3.7±0.5; P<0.0005), retroperitoneal location (HR=3.2±0.5; P<0.0005), and distant metastasis (HR=2.4±0.6; P=0.002), but not categorized tumor size (pT category), had the largest effects on sarcoma-specific survival. A new staging system based on these predictive factors demonstrated better discrimination between tumor stages, higher concordance with clinical outcomes, and greater predictive accuracy than the AJCC eighth edition staging system (86±1% vs. 83±2%; P=0.005). Statistical analysis of a large national cohort failed to confirm that categorized tumor size is a useful criterion by which to stage MDM2-amplified liposarcoma. A simplified staging system based on anatomic location and dedifferentiation outperforms the current AJCC staging system. Anatomic localization and histologic grade, and not tumor size, should be included in any future liposarcoma-specific staging system.

Development and validation of prognostic nomograms for pseudomyxoma peritonei patients after surgery: A population-based study.

Background:The aim of study was to develop and validate nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) of patients with pseudomyxoma peritonei (PMP) and compare the predictive accuracy with the American Joint Committee on Cancer (AJCC) staging system.Methods:Data of 4959 PMP patients who underwent surgical resection were collected between 2004 and 2015 from the Surveillance Epidemiology and End Results (SEER) database. All included patients were divided into training (n = 3307) and validation (n = 1652) cohorts. The Kaplan–Meier method and Cox proportional hazard model were applied. Nomograms were validated by discrimination and calibration. Finally, concordance index (C-index) was used to compare the predictive performance of nomograms with that of the AJCC staging system.Results:According to the univariate and multivariate analyses of training sets, both nomograms for predicting OS and CSS combining age, grade, location, N stage, M stage, and chemotherapy were identified. Nomograms predicting OS also incorporated T stage and the number of lymph nodes removed (LNR). The calibration curves showed good consistency between predicted and actual observed survival. Moreover, C-index values demonstrated that the nomograms predicting both OS and CSS were superior to the AJCC staging system in both cohorts.Conclusion:We successfully developed and validated prognostic nomograms for predicting OS and CSS in PMP patients. Two nomograms were more accurate and applicable than the AJCC staging system for predicting patient survival, which may help clinicians stratify patients into different risk groups, tailor individualized treatment, and accurately predict patient survival in PMP.

Diagnostic and prognostic values of upregulated SPC25 in patients with hepatocellular carcinoma.

BackgroundSpindle pole body component 25 (SPC25) plays a vital role in many cellular processes, such as tumorigenesis. However, the clinical significance of SPC25 in hepatocellular carcinoma (HCC) has not been investigated. This study aimed to explore the expression patterns of SPC25 in HCC and non-neoplastic tissues and to investigate the diagnostic and prognostic values of SPC25.MethodThe expression of SPC25 was examined in 374 HCC issues and 50 non-neoplastic tissues from The Cancer Genome Atlas (TCGA) cohort. The diagnostic and prognostic values of SPC25 were analyzed via receiver operating characteristic (ROC) curve and survival analyses, respectively. Univariate and multivariate Cox regression analyses were used to identify the prognostic factors and to establish a nomogram. The diagnostic and prognostic values were further validated in an external cohort from the International Cancer Genome Consortium (ICGC) database.ResultsThe expression of SPC25 in HCC tissues was significantly higher than that in normal tissues in both cohorts (all P < 0.001). The ROC curve analysis indicated that SPC25 expression has high diagnostic value in HCC with area under the curve (AUC) value of 0.969 (95% confidence interval [CI] [0.948–0.984]) and 0.945 (95% CI [0.920–0.965]) for TCGA and ICGC cohorts, respectively. Patients with HCC exhibiting high SPC25 expression were associated with worse prognosis than those exhibiting low SPC25 expression in both cohorts (all P < 0.001). SPC25 was independently associated with overall survival in both cohorts (all P < 0.001). The concordance indices of the nomogram for predicting overall survival in TCGA and ICGC cohorts were 0.647 and 0.805, respectively, which were higher than those of the American Joint Committee on Cancer (AJCC) staging system.ConclusionSPC25 was upregulated in HCC and independently predicted poor overall survival of patients with HCC. Therefore, SPC25 is an effective diagnostic and prognostic biomarker for HCC. An SPC25-based nomogram was more accurate and useful than the AJCC staging system to predict prognosis of HCC.

Prognostic role of ultrasonography staging in patients with anal cancer.

BACKGROUNDCarcinomas of the anal canal are staged according to the size and extent of the disease; however, we propose including a novel ultrasound (US) staging system, based on depth of tumor invasion. In this study the clinical American Joint Committee on Cancer (AJCC) staging guidelines and the US classificationss in patients with anal cancer were compared.AIMTo evaluate the prognostic role of the US staging system in patients with anal cancer.METHODSThe data of 48 patients with anal canal squamous cells carcinoma, observed at our University Hospital between 2007 and 2017, who underwent pre-treatment assessment with pelvic magnetic resonance imaging (MRI), total body computed tomography (CT) scan and endoanal US were retrospectively reviewed. Anal canal tumors were clinically staged according to AJCC, determined by MRI by measurement of the longest tumor diameter, and CT scan. Endoanal US was performed with a high multi-frequency (9-16 MHz), 360° rotational mechanical probe; US classification was based on depth of tumor penetration through the anal wall, according to Giovannini’s study. All patients were treated with definitive radiation combined with 5-fluorouracile and Mitomycin-C. After treatment patients were followed-up regularly.RESULTSAt baseline there were 30 and 32 T1-2, 18 and 16 T3-4, 31 and 19 N+ patients classified according to the clinical AJCC and US staging system respectively. After a mean follow-up of 98 months, 38 patients (79.1%) are alive and 28 (58.3%) are disease free. During follow up 20 patients (41.6%) experienced recurrences. After univariate analysis, American Society of Anesthesiologists (ASA) score (P = 0.00000001) and US staging (P = 0.009) were significantly related to disease-free survival (DFS). When overall survival and DFS functions were compared, a statistically significant difference was observed for DFS survival when the US staging was applied with respect to the clinical AJCC staging. By combining the 2 significant prognostic variables, namely the US staging with the ASA score, four risks groups with different prognoses were identified.CONCLUSIONOur findings suggest that US staging may be superior to traditional clinical staging, since it is significantly associated with DFS in anal cancer patients.

Compartmental Surgery With Microvascular Free Flap Reconstruction in Patients With T1-T4 Squamous Cell Carcinoma of the Tongue: Analysis of Risk Factors, and Prognostic Value of the 8th Edition AJCC TNM Staging System.

Compartmental surgery and primary reconstruction with microvascular free flaps represent the gold-standard in the treatment of oral tongue squamous cell carcinoma (OTSCC). However, there are still unclear clinical features that negatively affect the outcomes. This retrospective study included 80 consecutive patients with OTSCC who underwent compartmental surgery and primary reconstruction by free flap. The oncologic outcomes, the reliability of the 8th edition American Joint Committee on Cancer (AJCC) staging system and the prognostic factors were evaluated. Fifty-nine males and 21 females (mean age 57.8 years, range 27–81 years) were treated between November 2010 and March 2018 (one patient had two metachronous primaries). Seventy-one patients (88.75%, 52 males, 19 females, mean age of 57.9 years, range of 27–81 years) had no clinical history of previous head and neck radiotherapy and were considered as naive. Histology showed radical surgery on 80/81 lesions (98.8%), with excision margins >0.5 cm, while in 1 case (1.2%), a close posterior margin was found. According to the 8th AJCC classification, 37 patients (45.7%) were upstaged shifting from the clinical to the pathological stage, and 39 (48.1%) showed an upstaging while shifting from the 7th to the 8th AJCC staging system (no tumors were downstaged). Nodal involvement was confirmed in 33 patients (40.7%). Perineural and lymphovascular invasion were present in 9 (11.1%) and 11 (13.6%) cases, respectively. Twenty-two patients (27.1%) underwent adjuvant therapy. The 5-years disease-specific, overall, overall relapse-free, locoregional relapse-free and distant metastasis-free survival rates were 73.2, 66.8, 62.6, 67.4, and 86%, respectively. Patients with a lymph node ratio >0.09 experienced significantly worse outcomes. Univariate analysis showed that patients with previous radiotherapy, stage IV disease, nodal involvement, and lymphovascular invasion had significantly worse outcomes. Multivariate analysis focused naive patients and showed that lymphovascular invasion, advanced stage of disease, and node involvement resulted reliable prognostic factors, and patients with the same tumor stage and histological risk factors who did not undergo adjuvant therapy experienced significantly worse outcomes. In our series, surgery played a major role in the treatment of local extension; adjuvant therapy resulted strictly indicated in patients with advanced-stage disease associated with risk factors.

Clinicopathological Characteristics and Prognosis of Nasopharyngeal Lymphoepithelial Carcinoma: A Population-Based Retrospective Study

BackgroundThe aim of this study was to establish a predictive model for prognostic factors and overall survival (OS) in nasopharyngeal lymphoepithelial carcinoma (NLEC) patients.Material/MethodsThe data of 538 NLEC patients diagnosed between 1988 and 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Patients who were diagnosed from 1988 to 1999 were included in the validation cohort, and those diagnosed from 2000 to 2015 in the primary cohort. Least absolute shrinkage and selection operator and multivariate Cox regression analyses were performed. The discrimination and calibration capabilities of the predictive models were evaluated using the receiver operating characteristic (ROC) curve and calibration plot, respectively.ResultsRadiotherapy (P<0.0001), early-stage cancer based on the American Joint Committee on Cancer (AJCC) staging system (P<0.0001), younger age (P=0.0005) were associated with better OS rates. In the primary cohort, the areas under the ROC curves (AUC) of the nomogram for predicting 1-, 10-, and 15-year OS were 0.749, 0.754, and 0.81, respectively. Meanwhile, in the validation cohort, the AUC of the nomogram for predicting 1-, 10-, and 15-year OS were 0.692, 0.692, and 0.682, respectively. Furthermore, the calibration plot exhibited optimal agreements between the nomogram-predicted and actual 1-, 10-, and 15-year OS in both cohorts. The 1-, 10-, and 15-year OS rates were 93.6%, 62.7%, and 49.9%, respectively.ConclusionsAge, early-stage cancer based on the AJCC staging system, radiotherapy, and gender can be used to predict OS in nasopharyngeal lymphoepithelial carcinoma patients.

Validation of Stage N3 of the Eighth Edition AJCC Staging System for Nasopharyngeal Carcinoma.

To validate stage nodal (N)3 of the 8th edition American Joint Committee on Cancer (AJCC) staging system for nasopharyngeal carcinoma (NPC). This retrospective cohort study extracted NPC patients from the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Pathologically confirmed patients with complete data of level IV, N3a, and N3b lymph node metastasis were investigated. The included patients were divided into level IV, N3a, and N3b groups. Five-year overall survival (OS) and cancer-specific survival (CSS) were compared among the three groups. A total of 693 patients were included: 285 (41.13%) patients in the level IV group, 124 (17.89%) patients in the N3a group, and 284 (40.98%) patients in the N3b group. The 5-year OS (57.1%, 55.0%, and 55.2%) and CSS (64.4%, 63.5%, and 64.4%) were not different among the level IV, N3a, and N3b groups. Multivariate regression analysis revealed that N stage was not an independent prognostic factor for OS (hazard ratio [HR] = 1.03, 95% confidence interval [CI]: 0.91-1.17; P = .65) or CSS (HR = 1.03, 95% CI: 0.89-1.19; P = .70). Stage N3 of the 8th edition AJCC staging system for NPC is reasonable. III Laryngoscope, 131:535-540, 2021.

Added value of metastatic cervical lymph node group V in nodal staging of nasopharyngeal cancer.

Prognostic significance of posterior cervical lymph node metastasis in nasopharyngeal cancer is largely unknown. This study aims to determine the added prognostic significance of cervical lymph node group V to the standard American Joint Committee on Cancer (AJCC) staging system (eighth edition AJCC) of nasopharyngeal patients with cancer treated with intensity-modulated radiation therapy (IMRT) in terms of overall survival (OS), distant metastatic-free survival (DMFS), and disease-free survival (DFS). A retrospective cohort of 199 consecutively diagnosed nasopharyngeal patients with cancer treated with definitive radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) in the era of IMRT in a large university hospital in endemic area of Southeast Asia. Pre-treatment imaging studies were thoroughly re-evaluated and re-staged by a board-certified radiologist using radiographic criteria for cervical lymph node metastasis. T and N classifications were reclassified according to the eighth AJCC staging system. Group V (Va and Vb) cervical node was evaluated for its added prognostic significance. Cox's proportional hazard model was used to retrieve hazard ratio (HR), 95% confidence interval and P value for N classification. Harrell's C-statistic (concordance index) was used for test of discrimination and internal validation was calculated by bootstrap method. This study demonstrated greater separation of OS with HR of 6.75 (95%CI 1.94-23.51, P = .003) by using group Vb only as N3 compared to HR of 4.70 (95%CI 1.37-16.13, P = .014) by using current standard N3 disease (groups IV and Vb). Similarly, N2 with presence of Va shows worsened DFS with HR of 8.70 (95%CI 1.08-69.67, P = .042) compared to N2 without Va with HR of 5.93 (95%CI 0.76-46.00, P = .089). After incorporating cervical group V into nodal staging, the HR and 95%CI among each group was better separated than the eighth AJCC staging system but without significant improvement in C-index. Cervical lymph node group V is a potentially added prognostic factor to standard TNM staging.

Nomogram prediction of overall survival based on log odds of positive lymph nodes for patients with penile squamous cell carcinoma.

PurposeThis study aimed to establish a nomogram to predict the long‐term overall survival (OS) for patients with penile squamous cell carcinoma (PSCC).MethodThe PSCC patients receiving regional lymph node dissection (RLND) were enrolled from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The dataset of all eligible patients were used to develop the predictive model. The significant independent predictors were identified through Cox regression modeling based on the Bayesian information criterion and then incorporated into a nomogram to predicted 1‐, 3‐, and 5‐year OS. Internal validation was performed using the bootstrap resampling method. The model performance was evaluated using Harrell's concordance index (C‐index), calibration plots, integrated discrimination improvement (IDI), net reclassification improvement (NRI), and decision curve analysis (DCA).ResultsTotally, 384 eligible PSCC patients were enrolled from the SEER database. A nomogram for OS prediction was developed, in which three clinical variables significantly associated with OS were integrated, including age, N classification, and log odds of positive lymph nodes (LODDS). The C‐index of the nomogram (0.746, 95% CI: 0.702‐0.790) was significantly higher than that of the American Joint Committee on Cancer (AJCC) staging system (0.692, 95% CI: 0.646‐0.738, P = .020). The bootstrap optimism‐corrected C‐index for the nomogram was 0.739 (95% CI: 0.690‐0.784). The bias‐corrected calibration plots showed the predicted risks were in good accordance with the actual risks. The results of NRI, IDI, and DCA exhibited superior predictive capability and higher clinical use of the nomogram compared with the AJCC staging system.ConclusionWe successfully constructed a simple and reliable nomogram for OS prediction among PSCC patients receiving RLND, which would be beneficial to clinical trial design, patient counseling, and therapeutic modality selection.

A prognostic nomogram for the cancer-specific survival of patients with upper-tract urothelial carcinoma based on the Surveillance, Epidemiology, and End Results Database

BackgroundThe aim of this study was to establish a comprehensive nomogram for the cancer-specific survival (CSS) of patients with upper-tract urothelial carcinoma (UTUC) and compare it with the traditional American Joint Committee on Cancer (AJCC) staging system in order to determine its reliability.MethodsThis study analyzed 9505 patients with UTUC in the Surveillance, Epidemiology, and End Results (SEER) database. R software was used to randomly divided the patients in a 7-to-3 ratio to form a training cohort (n = 6653) and a validation cohort (n = 2852). Multivariable Cox regression was used to identify predictive variables. The new survival model was compared with the AJCC prognosis model using the concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA).ResultsWe have established a nomogram for determining the 3-, 5-, and 8-year CSS probabilities of UTUC patients. The nomogram indicates that the AJCC stage has the greatest influence on CSS in UTUC, followed by the age at diagnosis, surgery status, tumor size, radiotherapy status, histological grade, marital status, chemotherapy status, race, and finally sex. The C-index was higher for the nomogram than the AJCC staging system in both the training cohort (0.785 versus 0.747) and the validation cohort (0.779 versus 0.739). Calibration plotting demonstrated that the model has good calibration ability. The AUC, NRI, IDI, and DCA of the nomogram showed that it performs better than the AJCC staging system alone.ConclusionsThis study is the first to establish a comprehensive UTUC nomogram based on the SEER database and evaluate it using a series of indicators. Our novel nomogram can help clinical staff to predict the 3-, 5-, and 8-year CSS probabilities of UTUC patients more accurately than using the AJCC staging system.

Development and Validation of a Nomogram-Based Prognostic Evaluation Model for Sarcomatoid Hepatocellular Carcinoma.

Sarcomatoid hepatocellular carcinoma (SHC) is a rare subtype of liver cancer with extremely poor prognosis. This study aimed to identify the prognostic factors and develop an exclusive and efficient nomogram to predict cancer-specific survival (CSS) for SHC. The data on patients diagnosed with SHC from January 1973 to December 2015 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database, and these patients were included as the training cohort. Least absolute shrinkage and selection operator (LASSO) and Cox proportional hazards regression analyses were used to identify the prognostic risk factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were determined using concordance index (C-index), calibration curve, and receiver operating characteristic (ROC) curve. Decision curve analysis (DCA) was used to compare the clinical benefits of the prognostic evaluation model (PEM) with that of the American Joint Committee on Cancer (AJCC) staging system. The results were validated with an external validation cohort. In total, 116 patients with SHC were included in the training cohort. Multivariate Cox analysis revealed M stage (distant metastasis), primary tumor surgery, and chemotherapy to be associated with CSS, and along with tumor size, an integrated PEM was constructed. A calibration curve for the probability of survival showed good agreement between the nomogram and actual observation. The C-index value of the nomogram for predicting CSS and AJCC was 0.853 and 0.649, respectively. In the validation cohort, the C-index value of the PEM discrimination was better than that of the Barcelona Clinic Liver Cancer (BCLC) staging system, CLIP score, and Okuda staging system, and no statistical difference was observed with eighth edition of the AJCC staging system and Izumi staging system. The proposed four-factor nomogram of PEM could accurately predict the prognosis of SHC and could be used in clinical practice.

Tumor Size is an Independent Predictor of Mortality Risk in Differentiated Thyroid Cancer Patients with T4 Disease

Objective: The eighth edition of the American Joint Committee on Cancer (AJCC) guideline on the tumor-node-metastasis staging system has been applied in clinical practice for thyroid cancer since 2018. However, using these criteria, a few studies have shown no significant difference between stage III and IV diseases amongst the differentiated thyroid cancer (DTC) patients. Thus, we aimed to study the underlying reason behind this observation. Methods: Patients were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. The Cox proportional hazards regression model was used for the univariate and multivariate analyses to plot the Kaplan-Meier survival curves for overall survival (OS) and disease-specific survival (DSS). Results: A total of 1,431 patients had a median tumor size of 3.0 cm (range: 0.1 to 50 cm). When stratified by tumor size (≤2 cm, 2 to 4 cm, and >4 cm), lower survival rates were observed in patients with stage III (T4a) cancer and large tumor size than in those with stage IVA (T4b) cancer and small tumor size. Univariate and multivariate analyses showed that tumor size (≤4 cm versus >4 cm) is an independent prognostic factor for OS (P<.001) and DSS (P<.001) in DTC patients with T4a and T4b diseases. Conclusion: Tumor size is an independent prognostic factor for OS and DSS in DTC patients with T4 disease; tumor size-related modification of the T4 category can improve the AJCC staging system for DTC patient with stage III-IV diseases. Abbreviations: AJCC = American Joint Committee on Cancer; CI = confidence interval; DSS = disease-specific survival; DTC = differentiated thyroid cancer; FTC = follicular thyroid cancer; HR = hazard ratio; OS = overall survival; PTC = papillary thyroid cancer; SEER = Surveillance, Epidemiology, and End Results; TNM = tumor-node-metastasis.

A prognostic nomogram for pancreatic ductal adenocarcinoma patients' all-cause survival in a Surveillance, Epidemiology, and End Results analysis.

BackgroundThe American Joint Committee on Cancer (AJCC) staging system is not adequate for predicting the all-cause survival of patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to establish a comprehensive nomogram for PDAC and compare its prognostic ability with that of the AJCC 8th edition staging system.MethodsThis study identified 5,097 patients with PDAC in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016, and R software was used to divide them into training (n=3,567) and validation (n=1,530) cohorts. Multivariate Cox regression was used to select predictive variables. The concordance index (C-index), the area under the time-dependent receiver operating characteristics curve (AUC), the net reclassification improvement (NRI), the integrated discrimination improvement (IDI), calibration plotting, and decision-curve analysis (DCA) were used to compare the new survival model with the AJCC 8th edition prognosis model.ResultsAfter performing a multivariate Cox regression analysis, data on the age at diagnosis, marital status, primary site, pathology grade, regional nodes examined, AJCC stage, surgery status, adjuvant radiotherapy status, and adjuvant chemotherapy status were entered into the model and used to establish the nomogram. The C-index for the nomogram (0.668 for the training cohort and 0.670 for the validation cohort) was higher than those for the AJCC staging system (0.590 and 0.578, respectively). The AUC, NRI, IDI, calibration plotting, and DCA showed that the nomogram performed better than the AJCC staging system.ConclusionsWe have developed and validated a prognosis nomogram as a predictive model for PDAC patients provides significantly improved predictive performance and is superior to the latest AJCC 8th edition staging system.