Controversies in locoregional management of breast cancer with low volume pN0(i+) and pN1mi nodal disease

ABSTRACT

Introduction: The pathologic status of the axillary lymph nodes is an important prognostic factor in patients with breast cancer. With the transition from axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) for patients with clinically node negative breast cancer, there has been an increase in detection of pN0(i+) breast cancer with isolated tumor cells and pN1mi disease with micrometastatic nodal involvement. The prognostic impact of small volume nodal involvement and the role of locoregional radiotherapy, especially in the era of modern systemic therapy, are unclear.

Areas covered: This review examines contemporary data evaluating the prognostic impact of pN0(i+) and pN1mi breast cancer on locoregional recurrence and survival outcomes, then discusses controversies related to the use of adjuvant locoregional radiation therapy in the presence of low volume nodal disease. Relevant papers were identified by searching multiple engines for articles published since 2000.

Expert opinion: Sentinel lymph node biopsy without completion ALND is a standard surgical option for patients with pN0(i+) and pN1mi disease. The available evidence does not support routine use of adjuvant locoregional radiation therapy in patients with pN0i+ or pN1mi disease, but locoregional radiotherapy should be considered in the presence of concomitant high-risk features and patient factors.     

TNM classification and the need for revision of pN3a breast cancer

BackgroundAccording to the seventh edition of tumour-node-metastasis (TNM) classification, pN3a status in breast cancer patients consists of presence of an infraclavicular lymph node metastasis (LNM) and/or presence of ≥10 axillary LNMs. The aim of this study was to determine whether prognosis of pN3a based on at least an infraclavicular LNM differs from ≥10 axillary LNMs.MethodsData were obtained from the Netherlands Cancer Registry. All patients were diagnosed between 2005 and 2008 with primary invasive epithelial breast cancer and pN2a or pN3a status as pathologic result. Patients with pN3a were subdivided in pN3a based on at least an infraclavicular LNM or ≥10 axillary LNMs. Disease-free survival (DFS) included any local, regional or contralateral recurrence, distant metastasis or death within 5 years. Kaplan–Meier curves provided information on 5-year DFS and 8-year overall survival (OS). In addition, Cox proportional hazards model was used to measure the effect of relevant clinicopathological variables on DFS and OS.ResultsA total of 3400 patients with pN2a and 1788 patients with pN3a were included. In 83 patients, pN3a was based on at least an infraclavicular LNM (4.6%) and in 1705 patients because of ≥10 axillary LNMs (95.4%). After multivariable analyses, DFS and OS were inferior in patients with pN3a based on ≥10 axillary LNMs compared to infraclavicular LNM (DFS 48.8% versus 63.8%, hazard ratio [HR] 1.59, p = 0.036; OS 46.6% versus 63.9%, HR 1.46, p = 0.042). Furthermore, pN2a and pN3a based on infraclavicular LNM had comparable DFS and OS.ConclusionPN3a status based on an at least an infraclavicular LNM is rare, yet its prognosis is superior to ≥10 axillary LNMs. Reclassification of infraclavicular LNM in the next TNM should therefore be considered into pN2a.     

Lymph node ratio and pN staging in patients with node-positive breast cancer: a report from the Korean breast cancer society

Patients with node-positive breast cancer are currently classified according to pN stage. Lymph node ratio (LNR), the ratio of positive to total removed lymph nodes, maybe a more useful prognostic factor in these patients. We therefore compared LNR and pN staging as prognostic factors in patients with node-positive breast cancer. Using two large prospective databases of the Korean Breast Cancer Registry (KBCR) and the Asan Medical Center (AMC) Breast Cancer Center of patients with LN-positive breast cancer from 1988 to 2005, we compared the ability of LNR and pN stage to predict patient survival by Cox regression analysis in the overall patient cohort and in subgroups categorized by age and intrinsic subtype. Patients were categorized into low- (≤0.20), intermediate- (>0.20 and ≤0.65), and high-risk (>0.65) LNR groups. The difference in mortality risk was greater among LNR groups than among patients staged pN1, pN2, and pN3, as assessed by disease-free survival (DFS), cancer-specific survival (CSS), and overall survival (OS) rates. In contrast to LNR risk categories, the survival curves for pN1 and pN2 stage patients overlapped in those aged <35 years and those with her2/neu-enriched or triple-negative tumors. These findings were validated by analyzing a nationwide registry of 15,488 node-positive patients, which showed that patients with pN1 and intermediate LNR risk had poorer DFS (HR 1.7, 95% CI 1.4–2.2) and CSS (HR 1.6, 95% CI 1.1–2.2) than patients with pN2 and low LNR risk. LNR is a better predictor of prognosis than pN stage in women with breast cancer, especially in high-risk patients, including younger women and women with her2/neu-enriched or triple-negative tumors. Treatment decisions should be based on LNR rather than on pN stage.     

Predictors of long-term survival in pN3 gastric cancer patients

BACKGROUND AND OBJECTIVES: Patients with pN3 gastric cancer are classified as having a stage IV disease just by virtue of having more than 15 metastatic lymph nodes according to the 5th UICC cancer staging criteria. We tried to verify whether the pN3 gastric cancer patients truly constitute a homogeneous group with the same poor prognosis by looking for predictors of long-term survival within the group. METHODS: Medical records of 347 patients who had gastrectomy with D2/D3 lymph node dissection for gastric cancer and diagnosed with pN3 disease by pathology, between January 1987 and December 1997 were reviewed. Clinicopathologic prognostic variables were evaluated as predictors of long-term survival by univariate and multivariate analysis. RESULTS: The overall 5-year survival rate was 13.0% (95% CI, 9.3-16.6%). The extent of gastric resection and metastatic lymph node ratio were significant independent predictors of long-term survival on multivariate analysis. The 5-year survival rates for the subtotal and total gastrectomy groups were 18.2 and 8.8%, respectively. The 5-year survival rate according to the metastatic lymph node ratio was 20.2, 8.9, and 1.9% when the ratio was <0.33, 0.33-0.67, and > 0.67, respectively. CONCLUSIONS: Patients with pN3 gastric cancer appear to be a heterogeneous group with clinicopathologic predictors that identify subgroups with significantly different long-term prognoses. The metastatic lymph node ratio may serve as a valuable tool to predict the long-term prognosis of these patients.     

Serum carcinoembryonic antigen level in pN1 non-small cell lung cancer patients

BACKGROUND: Although the prognostic significance of the serum carcinoembryonic antigen (CEA) level in non-small cell lung cancer has been reported in several studies, it is unknown whether the serum CEA level is a prognostic determinant for pN1 disease or not. MATERIALS AND METHODS: Seventy patients with pN1 non-small cell lung cancer who received complete resection were reviewed. The preoperative serum CEA level was measured in all patients. RESULTS: The pN1 patients with pT2-4 disease, hilar node involvement, multiple N1 station and elevated serum CEA level (>5 ng/mL) had a significantly unfavorable prognosis. Although a serum CEA level higher than 5 ng/mL was not an independent prognostic determinant, more than 10 ng/mL was an independent factor by multivariate analysis. In patients with pT1-2N1 disease, a serum CEA level more than 10 ng/mL was also a prognostic determinant. CONCLUSION: An elevated serum CEA level, especially higher than 10 ng/mL, is a significant prognostic determinant for pN1 lung cancer patients.     

Proposal of a novel subclassification of pN3b for improvement the prognostic discrimination ability of gastric cancer patients

IntroductionIn the recent edition of TNM staging system, pN3b gastric cancer were separated into the staging system for better prognosis accuracy. The definition of pN3b contains a large range of metastasis lymph nodes (mLNs). However, few studies have evaluated the prognosis of pN3b patients and it remains unknown whether these patients were reasonably assigned into the same substage.Materials and methodsA total of 642 pN3b patients from a multi-institutional cohort in China were included. Disease-specific survival (DSS) was estimated using the Kaplan-Meier method and the Cox proportional hazards regression analysis was used to identify the independent prognostic factors. Restricted cubic spine model was used to specify the association between the continuous variables and the logarithm Hazard ratios (HRs). The optimal cut-off value of mLNs for DSS was identified using the X-tile software.ResultsThe 5-year DSS rate of total pN3b cohort was 15.4%. The smooth curves showed a non-linear association between the mLNs and the logarithm HRs. All pN3b gastric cancer patients were divided into two subclassifications (pN3b1: 16-24 mLNs, pN3b2: ≥25 mLNs). Significant survival difference was observed between two subclassifications (P = 0.048). Additionally, more LNs examined could decrease the death risk of pN3b patients and bring survival benefit only in pN3b1 patients, but not in pN3b2 patients.ConclusionsWe proposed a novel subclassification of pN3b patients, which assigned patients into two subclassifications with significant survival difference. Future study should explore the prognosis value based on this novel subclassification in TNM staging system.     

pN3b期胃癌亚分期预后评估的合理性研究

目的:第8版TNM分期将pN3b期患者纳入分期,这一变化提高了预后评估准确性.然而鲜有研究评价pN3b期患者的预后情况,并且pN3b期病例涵盖的淋巴结转移范围较广,而如此大范围的淋巴结转移患者纳入到同一分期中,其合理性仍属未知.方法:来自国内多中心的642例pN3b期患者纳入本次研究.采用Kaplan-Meier方法及...     

pN2Ⅲ期结直肠癌患者生存影响多因素分析

目的:分析影响pN2Ⅲ期结直肠癌患者预后的不同因素,为临床治疗提供参考。方法:回顾性分析2008年01月至2013年06月就诊于江苏大学附属宜兴医院的185例术后病理证实为pN2Ⅲ期的结直肠癌患者病例资料,对患者进行随访,利用Log-rank检验及COX比例风险模型分析临床各因素对患者预后的影响。结果:全组患者2、3、5年生存率分别为68.6%、30.8%、18.9%,中位无病生存时间（DFS）为12.4个月,中位生存时间（MST）为26.7个月。单因素分析结果显示,年龄、分化程度、脉管内癌栓、浸润深度、化疗、术后CEA水平与pN2 Ⅲ期结直肠癌患者预后相关(P<0.05）。多因素分析结果显示,分化程度（HR=0.567,95%CI:0.410～0.783,P=0.001）、脉管内癌栓（HR=0.617,95%CI:0.434～0.878,P=0.007）、浸润深度（HR=1.640,95%CI:1.331～2.022,P<0.001）、化疗（HR=2.488,95%CI:1.678～3.689,P<0.001）、术后CEA水平（HR=0.375,95%CI:0.266～0.530,P<0.001）是影响pN2 Ⅲ期结直肠癌患者预后的独立因素(P<0.05）。结论:pN2Ⅲ期结直肠癌患者预后较差,特别是肿瘤分化程度低、脉管内有癌栓、肿瘤浸润至全层以上及术后CEA升高患者,化疗可改善预后。     

Five-year survivors with resected pN2 nonsmall cell lung carcinoma

BACKGROUND: Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow-up periods. METHODS: Between 1981-1990, 178 patients with pN2 nonsmall cell lung carcinoma underwent complete resection with systemic lymph node dissection. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors were compared. RESULTS: Gender, the side that was operated on, location of the tumor, histologic type, or surgical procedure were not related to the ratio of 5-year survivors. However, T classification, skip metastasis, and the number of levels involved were associated with the ratio significantly. The authors also found that the location of the involved lymph node(s) affected the ratio. CONCLUSIONS: Even in the presence of pN2 disease, lung carcinoma patients with T1 tumors, skip metastasis, or single level mediastinal lymph node involvement, especially Level 4, Level 5, or Level 6 lymph nodes, had a relatively favorable prognosis and may be candidates for primary resection.     

Therapeutic strategy for patients with pN0 gastric carcinoma

BACKGROUND AND OBJECTIVES: The prognosis for patients with pN0 gastric cancer is moderately hopeful (expected 5-year survival: 80%). However, the relevant prognostic factors and most appropriate surveillance protocol have not been identified. METHODS: We investigated 733 gastric cancer patients without lymph node metastasis for prognostic factors by uni- and multi-variate analysis and by documenting causes of death and recurrence patterns. RESULTS: Univariate analysis revealed that age, tumor location, macroscopic appearance, tumor diameter, invasion depth, lymphatic invasion, and venous invasion affected prognosis. Multivariate analysis showed that age (> or = 60 years), ill-defined macroscopic appearance, and undifferentiated histological type independently reduced survival rates. Age (> or = 60 years) and undifferentiated histological type adversely influenced prognosis in 507 early gastric cancer patients whereas ill-defined macroscopic appearance adversely affected prognosis in 226 advanced cancer patients. Recurrence patterns in these patients were similar to those produced by lymph node metastasis. The predominant recurrence pattern was peritoneal dissemination, observed 2-3 years post-resection. CONCLUSIONS: This study identified adverse prognostic factors in pN0 gastric cancer patients. Randomized controlled studies of adjuvant chemotherapy are necessary to assess whether such therapy is beneficial for patients with adverse prognostic factors.     

The combined pN stage and breast cancer subtypes in breast cancer: a better discriminator of outcome can be used to refine the 8th AJCC staging manual

Background

pN stage and breast cancer subtypes (BCS) are both well-recognized prognostic indicators. Our previous work has highlighted that patients even with the same pN stage exhibited a significant survival difference in different BCS. Given this achievement, we hypothesized that a statistical interaction might exist between pN stage and BCS. The aim of this retrospective cohort study was to compare the prognostic value of the combined pN stage and BCS (pN_new stage) with either pN stage or BCS alone, and to determine if this combined new stage could serve as an alternative discriminator of outcome.

Methods

We combined pN stage and BCS to create a new variable named pN_new stage and then divided it into four groups: pN0_new, pN1_new, pN2_new, and pN3_new. Survival analysis was performed with the use of the Kaplan–Meier method and the log-rank test was used for univariate analysis. For multivariate analysis, cox proportional hazard models were applied, allowing for the estimation of disease-free survival (DFS). To assess discriminatory accuracy of the models, we compared the area under the receiver-operating characteristic curve (AUROC), the Akaike information criterion (AIC), and the Bayesian information criterion (BIC) values. Then, we used this pN_new stage to generate a TN_newM staging system according to the 7th AJCC staging system.

Results

A statistical interaction between pN stage and BCS was found. In multivariate survival analysis, the pN_new stage has been confirmed as an independent prognostic variable of 5-year DFS. The pN_new stage, with a smaller AIC or BIC value and larger AUROC, was a more powerful predictor of DFS than either pN stage or BCS alone. Results were validated in a separate cohort of patients. The TN_newM stage proposed in our present study was found comparable to the new 8th AJCC edition which includes anatomic T, N, and M plus tumor grade and the status of the biomarkers Her-2, ER, and PR with respect to prognostic value for breast cancer patients.

Conclusions

The pN_new stage (combined pN stage and BCS) appears to be a more powerful predictor and discriminator for the outcome of breast cancer, as compared to pN stage or BCS alone, and the TN_newM stage may serve as a simple, easy-to-use alternative to the 8th AJCC edition staging manual.

     

Use of tamoxifen in pT1a-pT1b, pN0 breast cancer.

PURPOSE: To evaluate if in low-risk breast cancer patients (pT1a-pT1b, pN0) tamoxifen can reduce local recurrence and improve survival. METHODS: Retrospectively 700 patients were analyzed. All patients were treated from 1980 to 2003 with conservative surgery plus radiotherapy at the University of Florence. No patients were treated with adjuvant chemotherapy. Tamoxifen was prescribed in 359 patients (51.3%). The crude probability of survival (or local recurrence) was estimated by using Kaplan-Meier method, and survival (or local recurrence) comparisons were carried out using Cox proportional hazard regression models. RESULTS: The univariate analysis for specific survival showed that only histological type and local recurrence were significant prognostic factors (log rank test: p=0.02 and p<0.0001, respectively). The Cox regression model by stepwise selection confirmed lobular histological type (p=0.008; HR: 3.83, 95% CI: 1.31-11.21) and local recurrence (p<0.001; HR: 9.05, 95% CI: 3.05-26.82) as independent prognostic factors for disease specific survival. For local disease free survival, multivariate analysis did not show any significant parameters. CONCLUSION: In our series tamoxifen did not seem to improve disease specific survival and local disease specific survival. The number of events in terms of death for cancer or in terms of local recurrence is too small in this group of patients. However, according to our results we suggest not to prescribe tamoxifen in patients affected by pT1a-pT1b, pN0 breast cancer.     

Impact of Adjuvant Treatment in pN3 Penile Cancer

AimsDue to the lack of high-quality evidence and consensus on adjuvant treatment for locoregionally advanced penile cancer, we reviewed the outcomes of pN3 patients to determine the suitable adjuvant treatment options.Patients and methodsAll consecutive pN3 penile cancer patients treated at our institution between January 2010 and December 2018 were reviewed to assess the impact of demographical, pathological and treatment factors on disease-free survival (DFS) and overall survival. The DFS and overall survival were estimated using the Kaplan–Meier method and association was tested using the Cox regression model (two-sided test with P < 0.05 considered significant).ResultsOf 128 patients, 31 (24%) had pelvic nodal involvement. Twenty-six patients (20.3%) received no adjuvant treatment, 40 (31.3%) received single modality adjuvant treatment and 62 (48.4%) received multimodality adjuvant treatment (a combination of chemotherapy and radiotherapy). At a median follow-up of 22 months, the DFS and overall survival were 55.4 and 62%, respectively. The best DFS and overall survival was noted with chemotherapy followed by concurrent chemoradiation (C-CTRT; 93% each). On multivariate analysis, both DFS and overall survival were worse with pelvic node involvement (2.2 [1.3–4], P = 0.027 and 2.2 [1.3–4], P = 0.027, respectively) and better with any adjuvant treatment (single modality: 3 [1.5–5.5], P < 0.001; multimodality: 3.1 [1.6–6], P < 0.001). C-CTRT was associated with improved DFS over chemotherapy alone (0.17 [0.4–0.78], P = 0.02) but not over radiotherapy alone (0.35 [0.07–1.6], P = 0.19). In patients with no pelvic nodes involved, chemotherapy and radiotherapy as single modalities were associated with similar DFS and overall survival. In patients with pelvic nodes, multimodality treatment was associated with better DFS than single modality treatment (0.3 [0.1–1], P = 0.05).Conclusion: pN3 penile cancer is a diverse prognostic group with poorer outcomes associated with pelvic nodes. Single modality adjuvant treatment may be adequate in inguinal nodes with extranodal extension, but multimodality treatment should be given in patients with pelvic nodal involvement.     

Clinical implications of lymph node micrometastasis in patients with histologically node-negative (pN0) esophageal carcinoma

BACKGROUND AND OBJECTIVES: Lymph node micrometastasis is frequently detected in resected specimens of esophageal squamous cell carcinoma (ESCC). The goal of this study was to evaluate the clinical implication of micrometastasis in patients with lymph node-negative (pN0) disease. METHODS: We examined the presence of micrometastasis in 2,511 lymph nodes from 53 patients with pN0 disease who underwent curative esophagectomy. All lymph nodes and the primary tumors were immunostained using an anticytokeratin antibody cocktail (AE1/AE3). RESULTS: Micrometastasis was detected in 18 lymph nodes (0.72%) from 14 patients (26.4%). Detection of micrometastasis was not associated with the depth of invasion or the differentiation or lymphatic invasion. Lymph nodes containing micrometastases were widely distributed, but the most frequently involved nodes were located along the lesser curvature of the stomach. Four patients with micrometastasis (29%) and the only two patients without micrometastasis (5%) had recurrence as lymph node metastases (P = 0.036). There were no significant differences in recurrence-free survival and disease-specific survival between patients with micrometastasis and patients without micrometastasis. CONCLUSIONS: These results show that micrometastasis might increase the risk of lymph node recurrence, but does not influence the survival of patients with pN0 ESCC.     

pN0期食管鳞癌血液微转移检测的临床意义

目的探讨pN0期食管鳞癌的血液微转移临床意义及其对预后的影响。方法提取血液标本总RNA,将mRNA反转录成cDNA,然后用实时荧光定量RT—PCR技术检测血液标本MMP-7 mRNA和hTERT mRNA表达,计算样本的△△Ct值,对40例N0期食管癌患者分别进行术后3、6、12个月跟踪随访复查。结果血液微转移与年龄、性别、癌肿长度等因素无相关关系,但与组织分化等级和pTNM分期间存在相关关系。随访结果显示单纯观察肿瘤不同侵犯深度与肿瘤术后转移（复发）率无相关性;随访术后6个月及12个月,血液微转移与否与肿瘤转移（复发）率有相关性（P〈0．05）,其中血液微转移阳性患者术后12个月肿瘤转移（复发）概率是阴性患者的6．44倍（OR=6．440,95％CI为1．547～26．822）。结论食管鳞癌患者血液微转移检测对早期诊断及预后判断具有重要意义。     

Lymph Node Ratio and pN Staging Show Different Superiority As Prognostic Predictors Depending on the Number of Lymph Nodes Dissected in Chinese Patients With Luminal A Breast Cancer

BackgroundThe lymph node ratio (LNR) classification has shown superiority to pN staging (the number of positive lymph nodes) in breast cancers, but it has not been examined according to whether sufficient lymph nodes have been dissected.MethodsAll Chinese patients with luminal A breast cancer with positive lymph nodes seen at Sun Yat-sen University Cancer Center between 1995 and 2009 were enrolled. Disease-free survival (DFS) and overall survival (OS) were the endpoints, and the patients were further classified into 2 groups according to whether ≤ 10 or > 10 lymph nodes were dissected.ResultsFor the whole group, the OS curves of the pN stages overlapped, whereas they were separated in the LNR survival curves. LNR was an independent prognostic factor for OS and DFS, whereas the pN stage was not. In the ≤ 10 lymph nodes dissected group, both OS and DFS curves were clearly separated in the pN staging but overlapped in the LNR classification. In the > 10 lymph nodes dissected group, LNR showed no overlap in the OS curves and was an independent prognostic factor of OS and DFS when compared with pN staging.ConclusionIn Chinese patients with luminal A breast cancer, LNR classification and the pN stage show different superiority as prognostic predictors according to whether > 10 or < 10 lymph nodes are dissected.     

Metastatic Axillary Lymph Node Ratio (LNR) is Prognostically Superior to pN Staging in Patients with Breast Cancer - Results for 804 Chinese Patients from a Single Institution

The number of axillary lymph nodes involved and retrieved are important prognostic factors in breast cancer.The purpose of our study was to investigate whether the lymph node ratio (LNR) is a better prognostic factor inpredicting disease-free survival (DFS) for breast cancer patients as compared with pN staging. The analysis wasbased on 804 breast cancer patients who had underwent axillary lymph node dissection between 1999 and 2008in Sun Yat-Sen University Cancer Center. Optimal cutoff points of LNR were calculated using X-tile softwareand validated by bootstrapping. Patients were then divided into three groups (low-, intermediate-, and high-risk)according to the cutoff points. Predicting risk factors for relapse were performed according to Cox proportionalhazards analysis. DFS was estimated using the Kaplan-Meier method and compared by the log-rank test. The5-year DFS rate decreased significantly with increasing LNRs and pN. Univariate analysis found that the pT ,pN, LNR, molecule type, HER2, pTNM stage and radiotherapy well classified patients with significantly differentprognosis. By multivariate analysis, only LNR classification was retained as an independent prognostic factor.Furthermore, there was a significant prognostic difference among different LNR categories for pN2 category,but no apparent prognostic difference was seen between different pN categories in any LNR category. Therefore,LNR rather than pN staging is preferable in predicting DFS in node positive breast cancer patients, and routineclinical decision-making should take the LNR into consideration.     

Factors influencing the outcomes of primary surgery with postoperative radiotherapy for pN2 oropharyneal squamous cell carcinoma

The purpose of this study was to examine treatment outcomes and define factors that influence survival in patients with pN2 oropharyngeal carcinoma. Fifty-five patients underwent primary surgery with postoperative radiotherapy between 1994 and 2009. Primary tumor sites were 36 tonsil, 13 base of tongue, 3 soft palate, and three posterior pharyngeal wall. There were 15, 26, 5, and 9 patients with stage T1 to T4 cancers, respectively. The N stage were 5 N2a, 37 N2b, and 13 N2c. The 5-year disease-specific survival rates were 66%. A significant positive correlation was found between high risk HPV status and extracapsular spread and disease-specific survival rates (HPV (+); 93% vs. HPV (-); 56%, p=0.031 and extracapsular spread (-); 93% vs. extracapsular spread (+); 50%, p=0.008, respectively). Primary surgery with postoperative radiotherapy can be achieved with favorable oncologic outcomes for pN2 oropharyngeal carcinoma. Factors that affected prognosis were HPV status and extracapsular spread.     

Frequency of therapy-relevant staging shifts in colorectal cancer through the introduction of pN1c in the 7th TNM edition

BackgroundpN1c is a novel N-category introduced for colorectal cancer (CRC) in current TNM (Tumour, Node, Metastasis) classification. It represents cancers displaying tumour deposits (TDs) in the fat but no involvement of lymph nodes. pN1c is integrated into the UICC (International Union Against Cancer) staging system and shifts previous stage II cancers (6th edition) to stage III. We investigated the frequency of upstaging and TD prognostic significance.Methods414 CRCs, consecutively collected during a population-based epidemiological study, TNM classified and UICC staged according to the 6th TNM edition were reinvestigated for TD presence. The association with survival was investigated after a median follow-up time of 5 years in multivariate analyses among nodal negative and positive cases.ResultsTDs were found in 103 (24.9%) cancers and were strongly associated with T-, N- and M-stages (p < 0.0001, each). Upstaging of previous stage II cancers by the presence of TDs (pN1c) was found in six of 140 cases (4.3% of stage II, 1.4% of all tumours). For stage III CRC, strongly reduced overall, CRC-specific and recurrence-free survival were observed with the presence of TDs (hazard ratios (HR) 2.29, 95% confidence interval 1.27–4.10, HR 2.51, 1.27–4.98, and HR 2.43, 1.32–4.48, respectively).ConclusionsUpstaging of CRCs through the introduction of pN1c occurs in less than 5% of previous stage II and less than 2% of all cancers. Given the biologic relevance of TDs, integration into the UICC staging relevant N-category is justified. The high prognostic impact of TDs, however, is not reflected in nodal positive cancers in both the TNM and UICC staging systems.