Staging Paradox and recurrence pattern among stage IIB, IIC, and IIIA Colon cancers: a retrospective cohort study.

PURPOSE: The survival rates of patients with stage IIB and IIC colon cancer are paradoxically inferior to that of patients with stage IIIA colon cancer. This study aimed to examine the oncological outcomes and investigate the factors that could affect the staging paradox among stage IIB, IIC, and IIIA colon cancers based on a 9-year cancer database. METHODS: Patients with stage IIB (pT4aN0M0), IIC (pT4bN0M0), or IIIA (pT1-2N1M0) colon cancer were retrospectively selected from a prospectively maintained medical database from January 2011 to December 2019. Factors that might influence the staging paradox, including radicality, harvested lymph nodes, and chemotherapy administration, were examined. RESULTS: A total of 282 patients (stage IIB, n = 59; stage IIC, n = 46; and stage IIIA, n = 177) were enrolled. Patients with stage IIB/C cancer demonstrated higher carcinoembryonic antigen levels, larger tumor size, more frequent tumor obstruction, and higher locoregional recurrence than those with stage IIIA cancer. With respect to 10-year locoregional recurrence-free survival and cancer-specific survival, patients with stage IIB and IIC cancers had significantly lower survival rates than did those with stage IIIA cancer (73.7% vs. 66.3% vs. 91.2%, P = 0.0003; 5.4% vs. 10.9% vs. 11.2%, P = 0.0023). The staging paradox persisted in patients who underwent R0 resection, had harvested lymph nodes ≥ 12, and received chemotherapy, as confirmed by multivariate regression analysis. CONCLUSIONS: Based on the inferior oncological outcomes and higher locoregional recurrence rate, this study highlighted the need for intensified cytotoxic chemotherapy specific to this recurrence pattern for patients with stage IIB/C colon cancer.

Survival paradox between stage IIB/C and stage IIIA colon cancer: is it time to revise the American Joint Committee on Cancer TNM system?

INTRODUCTION: A survival paradox between T4N0 (Stage IIB/IIC) and Stage IIIA colon cancer exists, even after adjusting for adequate lymph node (LN) retrieval and receipt of adjuvant chemotherapy (C). We conducted a large hospital-based study to re-evaluate this survival paradox based on the newest 8th edition staging system. METHODS: The National Cancer Data Base was queried to evaluate 35,606 patients diagnosed with Stage IIB, IIC, and IIIA colon cancer between 2010 and 2017. The Kaplan-Meier method and log-rank test were used to compare unadjusted overall survival (OS). Multivariable Cox proportional hazards model was used to determine the association of stage with hazard ratios adjusted for relevant demographic and clinical variables including ≥ 12 LNs retrieved and receipt of adjuvant chemotherapy. P value < 0.05 was considered statistically significant. RESULTS: The 5-year OS for optimally treated stage IIIA colon cancer (receipt of C) was 84.3%, which was significantly higher than stage IIB/C (≥ 12 LNs retrieved + C) (72.8%; P < 0.0001). Stage was an independent predictor of OS. Among optimally treated Stage IIIA patients, T1N1 had the best survival (90.6%) while stage T4bN0 (stage IIC) had the worst (70.9%) (P < 0.0001). Compared to stage IIB, stage IIC had a 17% increased risk of overall death while stage IIIA had a 21% reduction in death (P < 0.0001). CONCLUSION: Stage IIB/C and Stage IIIA survival paradox persists even after accounting for receipt of adjuvant chemotherapy and adequate lymph node retrieval. Future iteration of the TNM system should take this paradox into consideration.

Rural versus urban commuting patients with stage III colon cancer: is there a difference in treatment and outcome?

BACKGROUND: To evaluate if there are differences in outcomes for patients with stage III colon cancer in those from urban vs. rural commuting areas. METHODS: Data were evaluated on patients diagnosed with stage III colon cancer between 2012 and2018 from the Louisiana Tumor Registry. Patients were classified into rural and urban groups. Data on overall survival, time from diagnosis to surgery and time from surgery to chemotherapy, and sociodemographic factors (including race, age, and poverty level) were recorded. RESULTS: Of 2652 patients identified, 2159 were urban (81.4%) and 493 rural (18.6%). No age difference between rural and urban patients (p = 0.56). Stage IIIB accounted for 66.7%, followed by IIIC (21.6%) and IIIA (11%), with a significant difference between rural and urban patients based on stage (p = 0.02). There was no difference in the extent of surgery (p = 0.34) or tumor size (p = 0.72) between urban and rural settings. No difference in undergoing chemotherapy (p = 0.12). There was a statistically significant difference in receiving timely treatment for hospital volume (p < 0.0001) and poverty level (p < 0.0001), but no difference in time from diagnosis to surgery (p = 0.48), and time from surgery to chemotherapy (p = 0.27). Non-Hispanic Blacks were less likely to receive timely treatment when compared with non-Hispanic Whites for both surgery and adjuvant chemotherapy, (aHR 0.91, 95% CI 0.83-0.99) and (aHR 0.86, 95% CI 0.77-0.97), respectively. There was no difference in Kaplan-Meier overall survival curves comparing rural vs. urban patients (p = 0.77). CONCLUSIONS: There was no statistical difference in overall survival, time to surgery, and time to adjuvant chemotherapy between rural and urban patients with Stage III colon cancer.

LIBRETTO-432, a phase III study of adjuvant selpercatinib or placebo in stage IB-IIIA RET fusion-positive non-small-cell lung cancer.

Selpercatinib, a first-in-class, highly selective and potent central nervous system-active RET kinase inhibitor demonstrated clinically meaningful activity with manageable toxicity in pretreated and treatment-naive advanced/metastatic RET fusion-positive non-small-cell lung cancer (NSCLC). LIBRETTO-432 is a global, randomized, double-blind, phase III trial evaluating selpercatinib versus placebo in stage IB-IIIA, RET fusion-positive NSCLC, previously treated with definitive surgery or radiation; participants must have undergone available anti-cancer therapy (including chemotherapy or durvalumab) or not be suitable for it, per investigator's discretion. The primary end point is investigator-assessed event-free survival (EFS) in the primary analysis population (stage II-IIIA RET fusion-positive NSCLC). Key secondary end points include EFS in the overall population, overall survival, and time to distant disease recurrence in the central nervous system.

Selpercatinib is approved in multiple countries for the treatment of advanced or metastatic RET-altered lung cancers. Selpercatinib has shown promising efficacy and safety results in patients with advanced/metastatic RET fusion-positive NSCLC. This is a summary of the LIBRETTO-432 study which compares selpercatinib with placebo in patients with earlier stages (stage IB-IIIA) of RET fusion-positive NSCLC, who have already undergone surgery or radiotherapy and applicable adjuvant chemotherapy. This study is active and currently recruiting new participants. This trial will evaluate how long people live without evidence of cancer recurrence, both during and after treatment. Side effects will also be evaluated in this study. Clinical Trial Registration: NCT04819100 (ClinicalTrials.gov).

miRNA Profile and Bioinformatic Analysis for Diagnosis in Patients with Stage IIIA Colon Cancer.

Early diagnosis is a critical factor in deciding the outcome of colon cancer, as is the case with other types of cancers. Recent scientific developments have enabled the use of biomarkers for diagnosis and for designing treatment strategies for various cancer types. Further, identification of potential targets of these biomarkers will facilitate a better understanding of molecular processes. The aim of this study is to analyze microRNA expression profile, and through bioinformatic analyses determine the cellular processes of potential target genes and understand their molecular mechanism in stage IIIA colon cancer patients. The microRNA expression profiles of both normal and tumor tissues of seven patients were analyzed using the Affymetrix microarray system. The target genes were identified by performing a KEGG pathway analysis on eight miRNAs (hsa-miR-362-3p, hsa-miR-34c-5p, hsa-miR-34c-3p, hsa-miR-34a-3p, hsa-miR-19b-1-3p, hsa-miR-371a-5p, hsa-miR-941 ad hsa-miR-7-5p), which were selected through an array scan by using DIANA-miRPath v.3 bioinformatic analysis tool. Biological pathway and cellular component analyses were performed on 30 genes targeted by miRNAs using FunRich Gene Enrichment tool. These analyses indicated that the genes targeted by these eight miRNAs played a role in either cell communication (53%), signal transduction (60%) or apoptosis (20%) in stage IIIA colon cancer. Taken together, these data suggest that these miRNAs can be used as biomarkers in Stage IIIA colon cancer.

Surgical challenges in multimodal treatment of N2-stage IIIA non-small cell lung cancer.

Locally advanced non-small cell lung cancer, especially mediastinal lymph node metastasis-positive stage IIIA-N2 cancer, is a heterogeneous disease state characterized by anatomically locally advanced disease with latent micrometastases. Thus, surgical resection or radiotherapy alone has historically failed to cure this disease. During the last three decades, persistent efforts have been made to develop a suitable treatment modality to overcome these problems using chemotherapy and/or radiotherapy with surgical resection. However, the role of surgical resection remains unclear, and the standard treatment for stage IIIA-N2 disease is concurrent chemoradiotherapy. In general, adjuvant chemotherapy is indicated for completely resected pathological stage IB disease or lymph node metastasis-positive pathological stage II or IIIA disease. Platinum-based doublet cytotoxic chemotherapy is currently the standard regimen. Additionally, post-operative radiotherapy might be indicated for post-operatively proven mediastinal lymph node metastasis; i.e. clinical N0-1 and pathological N2 disease. With the remarkable progression that has recently been made in the field of chemotherapy, such as advances in molecular targeting agents and immune checkpoint inhibitors, the basic policy of chemotherapy has been shifting to personalized treatment based on the individual patient's oncogene driver mutation status, immune status and other parameters. The same trend is being seen in the treatment of stage IIIA-N2 disease. We should consider the past and upcoming results of several clinical trials to optimize the coming era of personalized treatment.

Clinicopathological and biomolecular characteristics of stage IIB/IIC and stage IIIA colon cancer: Insight into the survival paradox.

BACKGROUND: A survival paradox of stage IIB/IIC and IIIA colon cancer has been consistently observed throughout revisions of the TNM system. This study aimed to understand this paradox with clinicopathological and molecular differences. METHODS: Clinicopathological characteristics of patients with pathologically confirmed stage IIB/IIC or IIIA colon cancer were retrospectively reviewed from a database. Publicly available molecular data were retrieved, and intrinsic subtypes were identified and subjected to gene sets enrichment analysis (GSEA). RESULTS: Among the 159 patients included in the clinicopathological analysis, those at stage IIB/IIC had worse 3-year disease-free and overall survival than those at stage IIIA (59.3% vs 91.7%, P < 0.001 and 82.7% vs 98.5%, P < 0.001, respectively), even after adjusting for confounding factors. Data of 95 patients were retrieved from public databases, demonstrating a higher frequency of the microsatellite instable subtype in stage IIB/IIC. The consensus molecular subtype distribution pattern differed between the groups. The GSEA further suggested the protumor inflammatory reaction might be more prominent in stage IIB/IIC. CONCLUSIONS: The survival paradox in colon cancer was confirmed and appears to be a multifactorial phenomenon not attributed to a single clinicopathologic factor. However, the greater molecular heterogeneity in stage IIB/IIC could contribute to the poor prognosis.

Postoperative Radiotherapy for Resected Stage IIIA-N2 Non-small-cell Lung Cancer: A Population-Based Time-Trend Study.

INTRODUCTION: The value of postoperative radiotherapy (PORT) for resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial with few studies focusing on whether PORT always plays a part in clinical practice and generates benefits to patients across different time periods. We investigated this issue using the Surveillance, Epidemiology, and End Results Database (SEER) and assessed the temporal trends spanning 27 years. METHODS: Within SEER, we selected stage IIIA-N2 NSCLC patients who underwent a lobectomy or pneumonectomy and coded as receiving PORT or never receiving radiotherapy over three time periods: 1988 to 1996, 1997 to 2005, 2006 to 2014. For each period, survival analyses were performed and propensity score matching (PSM) was used in the potentially beneficial subgroup. RESULTS: 45.4% of 5568 eligible patients received PORT. The yearly PORT use rates varied largely from 27.8% to 74.4%. Overall survival (OS) was distinctly improved over the period. The application of PORT had a significant impact on survival only in period 1 and 3. In subgroup analysis, the OS benefit of PORT was significant in each period in patients with 50% or more lymph node ratio (LNR) both before (hazard ratios, and P values of 0.647, P = .002; 0.804, P = .008; 0.721, P < .001 for period 1, 2, 3, respectively) and after PSM (0.642, P = .006; 0.785, P = .004; 0.748, P = .003 for period 1, 2, 3, respectively). CONCLUSIONS: The benefits of PORT are lasting and stable throughout the years in patients with LNR of 50% or more. This might provide a clue on proper patient selection for PORT application.

Tailored management of stage IIIa non-small-cell lung cancer in the era of the 8th edition of the TNM classification for lung cancer.

Stage IIIA is a very heterogeneous group encompassing locally advanced disease with T3 and T4 tumors without any nodal involvement and very small T1a primary tumors with unilateral mediastinal lymphatic disease. Tailored management defines interdisciplinary management requiring board decisions, which can sometimes be difficult particularly in stage IIIa non-small-cell lung cancer (NSCLC). Lobectomy still is standard of care even for stage I NSCLC, which increasingly is implemented using minimally invasive surgical technique. On the other hand even locally extended tumors are today safely resected with low morbidity and mortality. According to the 2015 guidelines of the European Society of Thoracic Surgeons any kind of anatomical lung resection for lung cancer with curative intent has to be accompanied by formal mediastinal lymph node dissection. The transcervical route for complete bilateral mediastinal lymphadenectomy offers improved completeness of resection without the need for single lung ventilation and ideally supports the concept of minimally invasive surgery.

Male patients with resected IIIA-N2 non-small-cell lung cancer may benefit from postoperative radiotherapy: a population-based survival analysis.

AIM: Our analysis was performed to assess the efficacy of postoperative radiotherapy (PORT) on the survival for pathologic IIIA-N2 Non-small-cell lung cancer patients. PATIENTS & METHODS: We identified 2949 patients from 2004 to 2013 in the SEER database. Propensity score-matching was used to reduce the selection bias. Overall survival (OS), cancer-specific survival (CSS) and the factors associated with survival prognosis were evaluated. RESULTS: There was no significant difference in OS and CSS between PORT and non-PORT groups. However, subgroup analysis revealed an OS (p = 0.007) and CSS (p = 0.006) detrimental for male patients not receiving PORT. Multivariate analysis showed that old age, male sex, high pathologic grade, squamous carcinoma, bigger tumor size and larger number of positive lymph nodes had a negative impact on survival. CONCLUSION: PORT could improve OS and CSS in male patients with resected IIIA-N2 non-small-cell lung cancer.

Poor survival in stage IIB/C (T4N0) compared to stage IIIA (T1-2 N1, T1N2a) colon cancer persists even after adjusting for adequate lymph nodes retrieved and receipt of adjuvant chemotherapy.

BACKGROUND: A survival paradox between Stage IIB/C and Stage IIIA colon cancers exists. It is unclear how adequate lymph nodes dissection (LN) and post-surgery chemotherapy contribute to the survival paradox. We intended to assess the impact of these two factors on the survival paradox. RESULTS: We evaluated 34,999 patients diagnosed with stage IIIA or stage IIB/C colon cancer in 2003-2012 from the National Cancer Data Base. The 5-year overall survival (OS) was 73.5 % for stage IIIA and 51.1 % for stage IIB/C (P < 0.0001). The 5-year OS was 84.1 % for stage IIIA with post-surgery chemotherapy, 70.8 % for stage IIB/C with ≥ 12 LNs retrieved with chemotherapy, 53.9 % for stage IIB/C < 12 LNs with chemotherapy, 49.5 % for stage IIIA without chemotherapy, 43.7 % for stage IIB/C ≥ 12 LNs retrieved without chemotherapy, to 27.7 % for stage IIB/C < 12 LNs without chemotherapy. Even among stage IIB/C who had optimal treatment (≥12 LNs retrieved, received chemotherapy), OS remains lower than stage IIIA with chemotherapy. After adjusting LN dissection and chemotherapy in addition to the adjustment of other clinical factors, the survival paradox was reduced from HR = 1.76 (95 % CI: 1.68-1.85) to HR 1.51 (95 % CI: 1.44-1.59). CONCLUSIONS: LN dissection and post-surgery chemotherapy partially explained the survival paradox. More research is warranted to identify other factors that contribute to this paradox. Future iteration of TNM staging system should take this into consideration.

Distinctive oncological features of stage IIIA colorectal cancer: Analysis of prognostic factors for selective adjuvant chemotherapy.

INTRODUCTION: In the seventh TNM classification, stage IIIA includes tumors with early stage of bowel wall invasion and regional lymph node metastasis. We investigated the validity of the current TNM classification of patients with stage IIIA colorectal cancer and identified prognostic factors of them for ameliorating treatment strategies for them. METHODS: This study included the participation of four tertiary hospitals. A total of 4,236 patients with Stages I-IIIB colorectal cancer were analyzed. The primary end point was the 5-year relapse-free survival. RESULTS: The 5-year relapse-free survival of patients with stage IIIA disease was similar to that of patients with stage IIA. The 5-year relapse-free survival was 88.9% in the chemotherapy group (n = 152) and 82.3% in the no-chemotherapy group (n = 36, P = 0.111). Tumor differentiation (moderate or poor) and venous invasion were independent prognostic factors of relapse-free survival. CONCLUSIONS: The relapse-free survival of patients with stage IIIA tumors was similar to that of patients with stage IIA tumors, and the prognosis of stage IIIA tumors varied significantly by the tumor factors identified. These factors can be used to predict the risk of disease recurrence and to optimize the use of adjuvant chemotherapy.

The outcome and efficacy of adjuvant chemotherapy alone in patients with stage IIIA endometrial carcinoma with solitary adnexal involvement: a retrospective single-institution study.

OBJECTIVES: The appropriate adjuvant therapy for patients with endometrial carcinoma with solitary adnexal involvement is unclear. We conducted a retrospective single-institution study to evaluate the outcome and efficacy of adjuvant chemotherapy alone in this population. METHODS: All patients with endometrial carcinoma who received primary surgical treatment between January 1999 and May 2010 were reviewed. The patients who were diagnosed with stage IIIA disease based only on isolated adnexal involvement and treated with surgical procedures followed by adjuvant chemotherapy alone were included. Demographic, clinicopathologic, treatment and outcome data were collected. Recurrence and survival were analyzed. RESULTS: Among 1453 reviewed patients, 67 patients were identified. The median age was 48 years. All patients were treated with platinum-based adjuvant chemotherapy, with the majority (36/67, 53.7%) receiving paclitaxel plus carboplatin. The total number of cycles of chemotherapy administered was 305 (median four cycles/person). Most of the chemotherapy related toxicities were mild or moderate. The median follow-up time was 76 months. Eight patients experienced recurrence. The majority of initial relapses were distant (7/8, 87.5%), characterized by liver metastases (3/8, 37.5%). The 5-year disease-free survival (DFS) and overall survival (OS) rates were 89.6% and 91.9%, respectively. Multivariate analysis confirmed that grade 3 tumor was an independent predictor of worse DFS and OS (HR=5.19, P=0.048; HR=6.55, P=0.037, respectively). CONCLUSION: Patients with stage IIIA endometrial carcinoma with solitary adnexal involvement have favorable outcomes. Adjuvant chemotherapy alone may be effective and feasible for these patients.

Surgical outcomes after initial surgery for clinical single-station N2 non-small-cell lung cancer.

OBJECTIVE: Single-station N2 (Stage IIIA) non-small-cell lung cancer has been reported to have a relatively favorable prognosis after surgery. However, most previous studies examined surgical outcomes in N2 disease by pathologic nodal status but not by clinical nodal status. The objective of this study was to clarify the surgical outcomes in clinical single-station N2 non-small-cell lung cancer patients. METHODS: A total of 125 consecutive patients with clinical single-station N2 non-small-cell lung cancer were treated in our institution between 1992 and 2008. Among them, 97 (78%) patients underwent thoracotomy, and were included in this retrospective study. We defined clinical single-station N2 node as a node measuring 1-2 cm in a single mediastinal station observed on contrast-enhanced computed tomography. The median follow-up period was 5.9 years (range, 1.8-12.6). RESULTS: Eighty-eight (91%) patients underwent lung resection. Of them, 17 (19%) had true (pathologic) single-station N2 disease. Twenty-eight (32%) had pathologic multistation N2 and 43 (49%) had pN0-1 disease with favorable prognoses. The overall survival of the clinical single-station N2/pathologic N2 patients after initial surgery was unsatisfactory with a 5-year overall survival of 23.6%, but their prognoses were heterogeneous. True single-station pathologic N2 status (hazard ratio = 0.35, P = 0.008) and negative subcarinal node status (hazard ratio = 0.34, P = 0.022) were independent favorable prognostic factors after initial resection for clinical single-station N2/ pathologic N2 patients. The patients with both factors revealed a relatively favorable 5-year overall survival of 43.8%. CONCLUSION: Clinical single-station N2 status does not always correspond with pathologic true N2 status. From a prognostic point of view, initial surgery for clinical single-station N2 patients is indicated if their true single-station N2 status and negative subcarinal involvement are preoperatively confirmed.

[Resected non-small cell bronchogenic carcinoma stage pIIIA-N2. Which patients will benefit most from adjuvant therapy?]. / Carcinoma broncogénico no microcítico resecado, estadio pIIIA-N2. ¿En qué pacientes la adyuvancia ofrece mayor beneficio?

BACKGROUND: Controversy persists as regards the indications and results of surgery in the treatment of patients with stage pIIIA-N2 non-small cell lung cancer (NSCLC). The objective of this study was to analyze the overall survival of a multicentre series of these patients and the role of adjuvant treatment, looking for factors that may define subgroups of patients with an increased benefit from this treatment. METHODS: A retrospective study was conducted on 287 patients, with stage pIIIA-N2 NSCLC subjected to complete resection, taken from a multi-institutional database of 2.994 prospectively collected consecutive patients who underwent surgery for lung cancer. Adjuvant treatment was administered in 238 cases (82.9%). Analyses were made of the age, gender, histological type, administration of induction and adjuvant chemotherapy and/or radiation therapy treatments. RESULTS: The 5-year survival was 24%, with a median survival of 22 months. Survival was 26.5% among patients receiving with adjuvant treatment, versus 10.7% for those without it (P=.069). Age modified the effect of adjuvant treatment on survival (interaction P=.049). In patients under 70 years of age with squamous cell carcinoma, adjuvant treatment reduced the mortality rate by 37% (hazard ratio: 0,63; 95% CI; 0,42-0,95; P=.036). CONCLUSIONS: Completely resected patients with stage pIIIA-N2 NSCLC receiving adjuvant treatment reached higher survival rates than those who did not. Maximum benefit was achieved by the subgroup of patients under 70 years of age with squamous cell carcinoma.

Efficacy of Prophylactic Cranial Irradiation in Early to Mid-stage Small Cell Lung Cancer Patients in the Era of Magnetic Resonance Imaging.

BACKGROUND: Recent advancements in magnetic resonance imaging (MRI) for staging have highlighted the critical question of the need for prophylactic cranial irradiation (PCI) in managing early to mid-stage small cell lung cancer (SCLC). This study assesses the impact of PCI on overall survival (OS) and intracranial control among patients with stage I-IIB SCLC. METHODS: Data from 148 stage I-IIB SCLC patients treated with thoracic radiation therapy (TRT) at two centers were examined. Patients were categorized based on PCI administration: 63 received PCI, while 85 did not. All underwent pretreatment MRI, achieving at least a partial response to therapy. A 1:1 propensity score matching analysis corrected for potential biases. RESULTS: Propensity scores were generated to 116 patients, considering patient demographics, disease progression, and treatment methods. Death was included as a competing risk. The 3-year brain metastases (BM) occurrence rate was significantly higher in patients who did not receive PCI (30.0%) compared to those who did (14.8%), however, the difference was not statistically significant (No PCI vs. PCI, hazard ratio [HR]: 2.08, 95% CI [0.93-4.55], P = .07). No significant effect of PCI on OS was observed [PCI vs. No PCI, HR: 0.80, 95% CI (0.45-1.43), P = .45]. A subgroup analysis of stage IIB patients showed a significant increase in BM risk and mortality for those not receiving PCI (No PCI vs. PCI, BM risk HR: 5.85, 95% CI: 1.83-18.87, P = .003; mortality HR: 2.78, 95% CI: 1.14-6.67, P = .02), with less pronounced effects in stages I-IIA. CONCLUSION: With modern MRI-based screening, PCI may markedly benefit stage IIB SCLC patients by reducing BM and improving OS after initial sensitive treatment. This benefit does not appear to extend to stage I-IIA patients.

Revisiting the survival paradox between stage IIB/C and IIIA colon cancer.

Patients with stage IIB/C (T4a-bN0) colon cancer often exhibit worse survival rates compared to those with stage IIIA (T1-2N1, T1N2a) colon cancer. This study re-evaluates the survival paradox using the latest Surveillance, Epidemiology, and End Results (SEER) data (released on April 17, 2024) to inform potential revisions to the staging criteria. Utilizing SEER data with 8th edition TNM staging criteria, 4692 colon cancer patients diagnosed between 2018 and 2021 were analyzed with chi-square test. Cox regression and Kaplan-Meier survival analysis were employed to assess factors associated with cancer-specific survival (CSS) and overall survival (OS). The 3-year CSS rates for stage IIB and IIC were 73.1% and 70.3%, respectively, whereas stage IIIA had a substantially higher CSS rate of 91% (P < 0.001). Similarly, the OS rates were 64.9% and 63.0% for stage IIB and IIC, respectively, compared to 83.1% for stage IIIA (P < 0.001). Multivariate analyses revealed stage IIIA patients had significantly lower risks of cancer-specific mortality (hazard ratio (HR) = 0.374, 95% CI: 0.296-0.473, P < 0.001) and overall mortality (HR = 0.575, 95% CI: 0.483-0.685, P < 0.001) compared to stage IIB patients. The upcoming 9th edition of the AJCC staging system should address this paradox by integrating advanced diagnostic markers and emphasizing the aggressive biology of T4 tumor, providing more accurate prognostic information and guiding more effective treatment strategies for colon cancer patients.

Real-World Analysis of Survival and Treatment Efficacy in Stage IIIA-N2 Non-Small Cell Lung Cancer.

BACKGROUND: Stage IIIA-N2 non-small cell lung cancer (NSCLC) poses a significant clinical challenge, with low survival rates despite advances in therapy. The lack of a standardised treatment approach complicates patient management. This study utilises real-world data from Guy's Thoracic Cancer Database to analyse patient outcomes, identify key predictors of overall survival (OS) and disease-free survival (DFS), and address the limitations of randomised controlled trials. METHODS: This observational, single-centre, non-randomised study analysed 142 patients diagnosed with clinical and pathological T1/2 N2 NSCLC who received curative treatment from 2015 to 2021. Patients were categorised into three groups: Group A (30 patients) underwent surgery for clinical N2 disease, Group B (54 patients) had unsuspected N2 disease discovered during surgery, and Group C (58 patients) received radical chemoradiation or radiotherapy alone (CRT/RT) for clinical N2 disease. Data on demographics, treatment types, recurrence, and survival rates were analysed. RESULTS: The median OS for the cohort was 31 months, with 2-year and 5-year OS rates of 60% and 30%, respectively. Group A had a median OS of 32 months, Group B 36 months, and Group C 25 months. The median DFS was 18 months overall, with Group A at 16 months, Group B at 22 months, and Group C at 17 months. Significant predictors of OS included ECOG performance status, lymphovascular invasion, and histology. No significant differences in OS were found between treatment groups (p = 0.99). CONCLUSIONS: This study highlights the complexity and diversity of Stage IIIA-N2 NSCLC, with no single superior treatment strategy identified. The findings underscore the necessity for personalised treatment approaches and multidisciplinary decision-making. Future research should focus on integrating newer therapeutic modalities and conducting multi-centre trials to refine treatment strategies. Collaboration and ongoing data collection are crucial for improving personalised treatment plans and survival outcomes for Stage IIIA-N2 NSCLC patients.

Beneficial effects of postoperative radiotherapy for IIIA­N2 non­small cell lung cancer after radical resection analysed using the propensity score­matching method.

The objective of the present study was to investigate the role of postoperative radiotherapy (PORT) after radical resection of stage IIIA-N2 non-small cell lung cancer (NSCLC). Subgroups of patients who benefited from PORT were evaluated. A retrospective review of 288 consecutive patients with resected pIIIA-N2 NSCLC at Beijing Chest Hospital (Beijing, China) was performed. Of these patients, 61 received PORT. The 288 patients were divided into PORT and non-PORT groups according to the treatment received. The baseline characteristics of the two patient groups were balanced using propensity score-matching (PSM; 1:1 matching). In total, 60 patients in the PORT group and 60 patients in the non-PORT group were matched. After PSM, the median survival time of the matched patients was 53 months. The 1-, 3- and 5-year overall survival (OS) rates of the PORT patient group were 95.0, 63.2 and 48.2%, respectively, while those of the non-PORT group were 86.7, 58.3 and 34.5%, respectively, and there was no significant difference between the two groups (P=0.056). The 5-year local recurrence-free survival (LRFS) rate in the PORT group was significantly improved (P=0.001). The effects of PORT on OS and LRFS rates were analysed in patients with different clinicopathological features. For subgroups with multiple N2 stations, N2 positive lymph nodes ≥4 and squamous cell carcinoma, PORT significantly increased the OS and LRFS rates (P<0.05). In conclusion, there was no statistically significant improvement in the 5-year OS rate with PORT overall, but there may be subgroups, such as patients with multiple N2 stations, N2 positive nodes ≥4 and squamous cell carcinoma histology, that could be explored as potentially benefitting from improved 5-year OS and LRFS rates with PORT.

ER predicts poor prognosis in male lung squamous cell cancer of stage IIIA-N2 disease after sequential adjuvant chemoradiotherapy.

Introduction: The efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study. Methods: A total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay. Results: The median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors. Conclusions: PORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT.