Adjuvant chemotherapy is associated with improved overall survival in pelvic node–positive penile cancer after lymph node dissection: A multi-institutional study

ObjectivesWe determined whether adjuvant chemotherapy (AC) would be associated with improved survival after lymph node dissection (LND) for patients with penile cancer (PeCa) who have positive pelvic lymph nodes (PPLNs).MethodsWe retrospectively identified patients across 4 centers with penile squamous cell carcinoma who underwent LND from 1978 to 2013 and were found to have PPLNs. Patients who received chemotherapy before surgery or in the presence of recurrent disease were excluded. Cox regression was used to evaluate the association of AC with overall survival (OS), which was estimated using the Kaplan-Meier method. Differences in OS were determined with the log-rank test.ResultsDuring the study period, 141 patients who underwent LND for PeCa had PPLNs, and 84 of them met inclusion criteria. Median number of PPLNs was 2 (interquartile range [IQR]: 4–7), with 10% of cases occurring bilaterally and 55% having pelvic extranodal extension. AC was used in 36 (43%) patients. Patients who received AC were younger (P = 0.014), had less-aggressive penile tumor pathology (P<0.01), were less likely to receive adjuvant radiation (P<0.01), had less bilateral inguinal disease (P = 0.019), and had more inguinal extranodal extension (P = 0.042). Median follow-up was 12.1 months. Estimated median OS was 21.7 months (IQR: 11.8–104) in patients who received AC vs. 10.1 (IQR: 5.6–48.1) in those who did not (P = 0.048). AC was independently associated with improved OS on multivariate analysis (hazard ratio: 0.40; 95% CI: 0.19–0.87; P = 0.021).ConclusionsAC is associated with improved OS in patients with PeCa who have PPLNs after LND. Prospective studies are needed to demonstrate causality.     

Extranodal Spreading of Esophageal Squamous Cell Carcinoma: Clinicopathological Characteristics and Prognostic Impact

Background Microscopic cancer spreading to extranodal connective tissues (extranodal spreading: ENS) is occasionally found in resected specimens from patients with esophageal squamous cell carcinoma (SCC), but the prognostic impact of ENS remains unclear. The aims of this study were to elucidate the prognostic impact of ENS to help determine the most suitable management for the patients with ENS. Methods We histologically re-evaluated 7,349 lymph nodes obtained from 171 patients with SCC of the thoracic esophagus who underwent potentially curable resection between 1992 and 2003. We defined ENS as microscopic penetration of tumor cells from metastatic lymph nodes or tumor cell dissemination into extranodal connective tissues. Results Extranodal spreading was found in 37 (21.6%) patients, and it had a significant relationship with diameter and depth of the tumor, lymphatic and venous invasion, intramural metastasis, and number of metastatic nodes. Patients who were ENS positive were at higher risk of recurrence, and their overall survival rate was lower than that for ENS-negative patients. Furthermore, recurrent risk was higher and overall survival rate was lower in ENS-positive patients than in ENS-negative patients when they had 1–3 metastatic nodes, but recurrent risk and overall survival rate of the patients with 4 or more metastatic nodes were very similar in ENS-positive and ENS-negative patients. Conclusions The present findings suggest that in SCC of the thoracic esophagus, the presence of ENS increases recurrent risk and reduces the overall survival of the patients with 1–3 metastatic nodes. Patients showing ENS should be managed in the same way as patients with 4 or more metastatic nodes.     

Abdominal Lymph Node Metastasis in Patients with Mid Thoracic Esophageal Squamous Cell Carcinoma

Background  There are few reports about abdominal lymph node metastasis of mid thoracic esophageal carcinoma. This study was designed to explore the pattern of abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma and to evaluate the prognostic factors. Methods  The complete data of 368 patients with mid thoracic esophageal squamous cell carcinoma, who underwent modified Ivor-Lewis esophagectomy with two-field lymphadenectomy from January 1998 to January 2003, were reviewed. Survival rate was calculated by Kaplan-Meier method. Cox regression analysis was performed to identify risk prognostic factors. Results  Abdominal lymph node metastasis occurred in 58 (15.8%) patients: 34.5% (20/58) of them were stage T1 and T2. Skipping abdominal node metastasis was recognized in 13.8% (8/58) patients: all were stage T1 and T2. The overall 5-year survival rate of patients with abdominal lymph node metastasis (10.3%) was lower than that of those with thoracic node metastasis (18.3%). The prognosis of patients with distant abdominal lymph node metastasis was poor, and no one could survive more than 5 years. Cox regression analysis showed that five or more positive nodes and distant abdominal node metastasis were independent risk factors of patients with abdominal lymph node metastasis. Conclusions  Abdominal lymph node metastasis in patients with mid thoracic esophageal squamous cell carcinoma occurred frequently, and the surgery favorable for extensive abdominal lymph node dissection should be selected. The prognosis of patients with abdominal lymph node metastasis was poor, especially those with more positive nodes and distant abdominal node metastasis.     

胸中段食管鳞状细胞癌伴腹腔淋巴结转移及其预后的临床研究

目的 了解胸中段食管鳞状细胞癌伴腹腔淋巴结转移的方式,分析预后的影响因素.方法 对1998年1月至2003年1月接受手术治疗的368例胸中段食管鳞状细胞癌患者进行回顾性研究.本组男性289例,女性79例,年龄38～79岁,平均56岁.术前临床分期I～Ⅲ期.全部患者采用Ivor-Lewis手术(右胸及上腹部两切口)行食管大部切除加胸腹二野淋巴结清扫.全组患者平均随访时间68个月.结果 腹腔淋巴结转移58例(15.8%),其中T1-2患者占36.2%(21/58);有13.8%(8/58)的患者为跳跃性腹腔淋巴结转移,均发生在T1-2患者中.腹腔淋巴结转移患者5年生存率为10.3%,低于胸腔淋巴结转移患者的18.3%.远处腹腔淋巴结转移患者预后极差,无1例达到5年生存(0/16).COX多因素分析结果 显示,淋巴结转移数目≥5枚和远处腹腔淋巴结转移是腹腔淋巴结转移患者的独立预后因素.结论 胸中段食管癌腹腔淋巴结转移的发生率较高,应该选择有利于腹腔淋巴结广泛清扫的手术方式.腹腔淋巴结转移患者的预后不良,尤其淋巴结转移数目较多和远处淋巴结转移的患者预后更差.     

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010

ObjectivesThe prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis.MethodsThe phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy.ResultsIn total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence.ConclusionsPrerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.     

Impact of the Number and Extent of Positive Lymph Nodes in 200 Patients with Thoracic Esophageal Squamous Cell Carcinoma after Three-field Lymph Node Dissection

Background Subtotal esophagectomy with three-field lymph node dissection (3FLD) has been reported to improve survival in patients with thoracic esophageal squamous cell carcinoma (SCC). The purpose of this study was to evaluate the prognostic impact of the extent and number of positive lymph nodes for long-term survival of patients who underwent 3FLD. Methods From January 1983 to December 2002, a total of 200 patients with thoracic esophageal SCC underwent 3FLD without any neoadjuvant therapy. The prognostic impact of the extent and number of positive lymph nodes was evaluated by both univariate and multivariate analysis. Results The extent of positive nodes associated with a 5-year survival were as follows: none, 69%; one-field, 50%; two-field, 29%; and three-field, 11%. The number of positive nodes associated with 5-year survival were as follows: single node, 65%; two-nodes, 51%; and more than three-nodes, 20%. Among patients with cervical lymphatic spreading, patients with upper tumors showed significantly better survival than patients with lower tumors (P = 0.036). Multivariate analysis indicated that number of positive nodes and the abdominal node status were independent prognostic factors among lymph node status. Conclusions Together, number and extent of positive lymph nodes can be considered an independent predictor of a high risk of recurrence. Although cervical lymphatic spreading was risk factor for worse survival, patients with upper tumors may have survival benefit after cervical lymph node dissection.     

Impact of subcarinal dissection on short-term outcome and survival following esophagectomy

Background

The purpose of this study was to investigate the impact of subcarinal dissection on short-term outcomes and survival after esophagectomy in patients with thoracic esophageal squamous cell carcinoma.

Methods

Patients without subcarinal dissection were matched randomly to patients with subcarinal dissection in a 1:1 ratio according to 5 baseline variables (gender, pathologic stage, tumor location, histologic grade, and surgical approach) that may have major impacts on short-term outcomes and survival after esophagectomy in patients with thoracic esophageal squamous cell carcinoma. Preoperative clinical characteristics, short-term outcomes, and survival after esophagectomy of the 2 groups were compared.

Results

There were 128 patients included in each group. Blood loss, postoperative pleural drainage volume, and the incidences of postoperative complications and pulmonary complications in the nondissection group were significantly less than in the dissection group. The comparison of overall survival curves and disease-free survival curves between the 2 groups showed no significant difference (P > .05).

Conclusions

Subcarinal dissection might be futile for patients with thoracic esophageal squamous cell carcinoma.     

Tumor stiffness measurement using magnetic resonance elastography can predict recurrence and survival after curative resection of hepatocellular carcinoma

BackgroundTumor stiffness measurement using magnetic resonance elastography can assess tumor mechanical properties and predict hepatocellular carcinoma recurrence. This study aimed to investigate preoperative tumor stiffness on magnetic resonance elastography as a predictor of overall survival and recurrence-free survival in patients with solitary nodular hepatocellular carcinoma who underwent curative resection.MethodsSeventy-eight patients with solitary nodular hepatocellular carcinoma who underwent preoperative magnetic resonance elastography and curative resection were retrospectively analyzed. Potential associations of tumor stiffness and other clinicopathological variables with overall survival and recurrence-free survival were analyzed in both univariate and multivariate Cox proportional hazards analyses. The optimal tumor stiffness cutoff value was determined using the minimal P value approach.ResultsIn multivariate analysis, tumor stiffness (hazard ratio 1.31; 95% confidence interval, 1.07–1.59; P = .008) and vascular invasion (hazard ratio 2.62; 95% confidence interval, 1.27–5.17; P = .010) were independent predictors of recurrence-free survival. For overall survival, tumor stiffness (hazard ratio, 1.33; 95% confidence interval, 1.02–1.76; P = .037) was the only independent predictor. The optimal tumor stiffness cutoff value was 5.81 kPa for both overall survival and recurrence-free survival. Patients with tumor stiffness ≥5.81 kPa had a significantly greater risk of death (hazard ratio 6.10; 95% confidence interval, 2.11–21.90; P < .001) than those with tumor stiffness <5.81 kPa.ConclusionPreoperative tumor stiffness as measured by magnetic resonance elastography was a predictor of overall survival and recurrence-free survival in hepatocellular carcinoma patients who underwent curative resection. Higher tumor stiffness was associated with higher risk of recurrence and death.     

Correlation Between gp96 Expression and the Surgical Outcome in Patients With Esophageal Squamous Cell Carcinoma

Background

Heat-shock protein gp96 plays an important role in antitumor immunoreactions. Gp96 has a close relationship with antitumor immunity. This study evaluated the correlation between gp96 expression and the prognosis in esophageal squamous cell carcinoma.

Methods

Seventy-eight patients with primarily resected esophageal squamous cell carcinoma were enrolled onto this study, and gp96 expression was evaluated by immunohistochemical staining. The association of clinicopathological factors and patients’ survival was calculated by univariate (log rank test) and multivariate (Cox proportional hazard regression method) analyses.

Results

Fifty-seven (73%) of 78 cases were gp96 positive, and 21 were negative (27%). The survival of patients with gp96-negative disease was significantly shorter (5-year survival, 22.9 months) than with gp96-positive disease (45.8 months; P = 0.049), and the multivariate analysis showed that gp96 negativity is an independent risk factor for poor survival (hazard ratio, 2.577; P = 0.040). Gp96-negative cases had more metastatic lymph nodes than did negative cases, especially in T1 cases (4.8 in gp96-negative cases vs. 0.84 in gp96-positive cases; P = 0.064)

Conclusions

The downregulation of gp96 expression is closely correlated with poor survival in esophageal squamous cell carcinoma.     

Treatment outcome and prognosis of patients with lymph node recurrence of thoracic esophageal squamous cell carcinoma after curative resection

Background  

This study aimed to assess treatment outcome and factors influencing survival after lymph node recurrence of thoracic esophageal squamous cell carcinoma (SCC) after curative resection.     

Perigastric lymph node metastasis does not affect the survival of squamous cell carcinoma of the oesophagus treated with two‐field oesophagectomy

Aim: There are some discrepancies as to the prognostic value of perigastric lymph node (LN) metastasis in the survival of squamous oesophageal carcinoma. The present study aimed to compare survival following standard oesophagectomy in the treatment of squamous oesophageal carcinoma with or without perigastric abdominal LN metastasis. Methods: From 1998 to 2003, 17 patients with squamous cell carcinoma of the mid or lower oesophagus who had abdominal LN metastasis upon pathological examination underwent Ivor Lewis oesophagectomy. They did not receive further adjuvant therapy. The clinical outcomes of this cohort were compared to a control of 34 patients of similar age, gender and T staging who had no perigastric nodal diseases upon oesophagectomy. Results: There was no significant difference between the two groups in terms of the demographics, tumour size, differentiation of the tumour, duration of operation, volume of blood loss, and the type of oesophagectomy. The cumulative 3‐year survival rate was similar between those with abdominal LN metastasis or those without abdominal LN metastasis (52.9% vs 47.1%; log–rank test P = 0.61).There was also no significant difference in the rates of recurrence between the two groups (58.8% vs 58.8%; P = 0.1). Conclusions: Perigastric LN metastasis over the lesser curvature, left gastric artery and pericardial regions does not affect the survival of patients with squamous cell carcinoma of the oesophagus treated by two‐field oesophagectomy.     

Laser ablation as monotherapy for penile squamous cell carcinoma: A multi-center cohort analysis

Introduction

Although the trend towards penile sparing therapy is increasing for penile squamous cell carcinoma, outcomes for laser ablation therapy have not been widely reported. We assessed the clinical outcomes of penile cancer patients treated with only laser ablation.

Surgical outcome after the clearance of abdominal metastatic lymph nodes in 138 patients with thoracic esophageal carcinoma

BACKGROUND: Although abdominal lymph node metastasis in patients with thoracic esophageal squamous cell carcinoma (SCC) has been reported to be a risk factor to reduce long-term survival, only a few studies have so far evaluated the clinicopathologic factors among this group of patients. The purpose of this study was to evaluate the patients' surgical outcome after the clearance of metastatic abdominal nodes. PATIENTS AND METHODS: From 1980 to 2002, 550 consecutive patients with thoracic esophageal SCC underwent surgery with an abdominal lymph node dissection. A total of 138 patients with abdominal lymph node metastases were curatively resected. Those patients, including 62 from 1980 to 1989 and 76 from 1990 to 2002, were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the impact of clinicopathologic factors on the survival of these patients. RESULTS: The overall 5-year survival rate of the 138 patients with abdominal lymph node metastases was 23%. A univariate analysis revealed that the following groups showed a greater than 30% overall 5-year survival rate: patients with T1 or T2 tumors, patients without thoracic node metastases, and those with poorly differentiated type tumors. Good prognostic factors based on a multivariate analysis were the most recent time period of surgery and 4 or fewer positive nodes. CONCLUSION: Among the patients with abdominal lymph node metastases, those with T1 or T2 tumors, patients without thoracic node metastases, and patients with 4 or fewer positive nodes showed an acceptable overall survival after a curative resection.     

Impact of micropapillary urothelial carcinoma variant histology on survival after radical cystectomy

ObjectivesThe role of micropapillary urothelial carcinoma (MUC) variant histology as an independent prognostic factor for survival after radical cystectomy has not been studied. Our aim was to examine the impact of MUC on survival.Materials and methodsA retrospective analysis of prospectively collected data from the University of Southern California (USC) Bladder Cancer Database was performed. Between 1985 and 2008, 1,380 patients underwent radical cystectomy and superextended pelvic lymph node dissection for bladder cancer. All surgical specimens underwent central pathologic review by dedicated genitourinary pathologists. Histologic type was categorized as urothelial carcinoma (UC; n = 1,347) or MUC (n = 33). The outcomes were overall survival (OS) and recurrence-free survival (RFS). The Kaplan-Meier method and Cox proportional regression models were used to analyze survival data.ResultsThe median follow-up duration was 10 years (range, 0–25 years). Baseline characteristics were similar between histologic types except MUC was associated with advanced clinical (cTanyN1–3: 2% vs. 9%, P = 0.03) and pathologic (pTanyN1–3: 22% vs. 46%, P = 0.01) TNM stage, multifocality (38% vs. 58%, P = 0.02), and high nuclear grade (83% vs. 97%, P = 0.03). The predicted 5-year OS (61% and 67%, Log rank P = 0.96) and RFS (69% and 58%, Log rank P = 0.33) rates did not differ between patients with UC and MUC. Multivariable analysis showed that histologic type was not independently associated with OS (HR 0.91, 95% CI 0.55–1.49, P = 0.70) or RFS (HR 0.97, 95% CI 0.55–1.73, P = 0.92).ConclusionsOutcomes of radical cystectomy for patients with MUC are similar to those with UC when controlling for other clinical and pathologic factors.     

Effect of age on the clinical outcomes of patients with early gastric cancer with undifferentiated-type histology

Background

Undifferentiated-type early gastric cancers account for a large proportion of gastric cancers in younger patients. Therefore, the clinical outcomes of endoscopic resection in younger patients are a major concern. We aimed to investigate the influence of age on lymph node metastasis and long-term survival after surgery for undifferentiated-type early gastric cancers.

Extranodal extension in node-positive bladder cancer: the continuing controversy

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Although extranodal extension in node‐positive patients may provide prognostic information in certain urological malignancies, contradictory results have been reported in node‐positive patients after radical cystectomy for bladder cancer. We examined whether extranodal extension could have an impact on the outcomes of node‐positive patients who underwent radical cystectomy for bladder cancer in a single large tertiary hospital. We have shown that the presence of extranodal extension was not an independent prognostic factor in node‐positive patients after radical cystectomy and pelvic lymphadenectomy for bladder cancer.

OBJECTIVE

? To examine whether extranodal extension (ENE) has an impact on the outcome of node‐positive patients who underwent radical cystectomy for bladder cancer.

PATIENTS AND METHODS

? Of 543 consecutive patients who underwent radical cystectomy for urothelial carcinoma of the bladder between 1990 and 2007, 112 patients with lymph node metastasis detected on histological examination were evaluated with regard to recurrence‐free survival (RFS) and disease‐specific survival (DSS) based on ENE status.

RESULTS

? The overall 5‐year RFS and DSS rates were 22.3% and 33.8%, respectively. ENE was observed in 41 (36.6%) of the 112 patients. ? The presence of ENE was associated with advanced pathological nodal status (P= 0.004), more positive lymph nodes (P= 0.006), and higher lymph node density (P < 0.001). ? The incidence of positive ENE increased with large positive lymph node diameter (P < 0.001). ? Multivariate analysis showed that lymph node density (hazard ratio (HR) = 2.39, 95% CI 1.09–5.24, P= 0.029; and HR = 3.13, 1.43–6.84, P= 0.004) and use of adjuvant chemotherapy (HR = 1.80, 1.02–3.20, P= 0.041; and HR = 2.07, 1.13–3.79, P= 0.018) were significant predictors of RFS and DSS, respectively. ? After adjustment for other prognostic factors, ENE was not significantly related to RFS (P= 0.825) and DSS (P= 0.961) by multivariate analysis.

CONCLUSIONS

? The presence of ENE was not an independent prognostic factor in node‐positive patients after radical cystectomy for bladder cancer. ? Additional prospective studies are needed to determine the independent prognostic role of ENE.     

Clinicopathologic Characteristics and Clinical Outcomes of Esophageal Basaloid Squamous Carcinoma: Experience at a Single Institution

This retrospective study investigated the clinicopathologic characteristics and clinical outcomes of esophageal basaloid squamous carcinoma (BSC). Among 190 patients with esophageal carcinoma treated surgically between 1998 and 2011, we identified 9 (4.7%) with BSC. All of the patients were male, with a median age of 65 years. The frequencies of venous invasion, lymphatic invasion, and lymph node metastasis were 56%, 89%, and 67%, respectively. A total of 2 patients were pathologic stage 1, 5 were stage 2, and 2 were stage 3. Tumor recurrence was observed in 56% of the patients. The 5-year survival rate for patients with esophageal BSC was 40%, which was compatible with the figure of 53.8% for control patients (n = 18) with typical squamous cell carcinoma matched for sex, age, tumor location, and pathologic stage (P = 0.45). Although esophageal BSC shows aggressive lymph-vascular invasion and has a high likelihood of recurrence, its prognosis seems identical to that of typical squamous cell carcinoma.     

胸段食管鳞癌患者的喉返神经旁淋巴结转移特点

目的探究胸段食管鳞癌患者的喉返神经旁淋巴结转移特点。 方法回顾性分析福建协和医院胸外科2012年1月至2015年12月间收治的行胸腹腔镜联合食管癌切除术的294例胸段食管鳞癌患者的喉返神经旁淋巴结清扫及转移情况,并分析喉返神经旁淋巴结转移特点。 结果294例行喉返神经旁淋巴结清扫的患者中,有88例患者有喉返神经旁淋巴结转移,转移率为29.93%;共清扫喉返神经旁淋巴结1 899枚,转移淋巴结145枚,转移度为7.64%。胸段食管鳞癌患者左、右喉返神经旁淋巴结转移与肿瘤浸润深度、分化程度、脉管瘤栓均有显著相关性(P<0.05),但与性别、年龄、肿瘤部位无显著相关性(P>0.05)。 结论胸段食管鳞癌患者易发生喉返神经旁淋巴结转移。对于肿瘤浸润程度大、分化程度差、有脉管瘤栓的胸段食管鳞癌患者,应重视左、右两侧喉返神经旁淋巴结清扫。     

Prognostic Implications of Pathological Lymph Node Status After Preoperative Chemotherapy for Operable T3N0M0 Breast Cancer

Background: Although preoperative chemotherapy has become the standard of care for inoperable locally advanced breast cancer, its role for downstaging resectable primary tumors is still evolving. The purpose of this study was to determine whether the prognostic information from an axillary node dissection in patients with clinical T3N0 breast cancer was altered by preoperative chemotherapy compared with surgery de novo.Methods: Between 1976 and 1994, 91 patients with clinically node-negative operable T3 breast cancer received doxorubicin-based combination chemotherapy on protocol at one institution. Fifty-three patients received both preoperative and postoperative chemotherapy (PreopCT), and 38 received postoperative chemotherapy only (PostopCT). All patients underwent axillary lymph node dissection as part of their definitive surgical treatment. There were no differences between the PreopCT and PostopCT groups in median age (51 vs. 49 years), median tumor size at presentation (6 cm vs. 6 cm), tumor grade, or estrogen receptor status (estrogen receptor negative 38% vs. 32%). The median follow-up time was 7 years.Results: Patients in the PreopCT group had fewer histologically positive lymph nodes (median, 0 vs. 3, P < .01), and a lower incidence of extranodal extension (19% vs. 42%, P 5 .02). By univariate analysis, the number of pathologically positive lymph nodes (P < .01) and extranodal extension (P < .01) were predictors of disease-specific survival in PreopCT patients. Multivariate analysis showed that extranodal extension was the only independent prognostic factor in PreopCT patients (P < .01). Overall, PreopCT and PostopCT patients had similar 5-year disease-free survival rates (66% vs. 57%); however, PreopCT patients had worse disease-free (P 5 .01) and diseasespecific survival (P 5 .04) when survival was compared after adjustment for the number of positive lymph nodes. Furthermore, PreopCT patients with 4–9 positive lymph nodes had a lower 5-year disease-free survival rate than PostopCT patients with 4–9 positive nodes (17 vs. 48%, P 5 .04).Conclusions: Axillary lymph node status remains prognostic after chemotherapy. Pathologically positive lymph nodes after preoperative chemotherapy are associated with a worse prognosis than the same nodal status before chemotherapy.     

Infiltration of CD3+ and CD68+ cells in bladder cancer is subtype specific and affects the outcome of patients with muscle-invasive tumors

ObjectivesUrothelial carcinoma (UC) aggressiveness is determined by tumor inherent molecular characteristics, such as molecular subtypes, as well as by host reactions directed toward the tumor. Cell types responsible for the host?s response include tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). The aim of the present investigation was to explore the immunological response in relation to UC molecular subtypes and to evaluate the prognostic effect of TIL and TAM counts in tissue sections from muscle-invasive (MI) tumors.Methods and materialsTissue microarrays with 296 tumors spanning all pathological stages and grades were analyzed with antibodies for CD3, CD8, FOXP3, CD68, and CD163. Cases were classified into the following molecular subtypes: urobasal, genomically unstable, and squamous cell carcinoma–like using a combination of immunohistochemistry and histology. The Cox regression and Kaplan-Meier analyses were performed with progression-free survival and disease-specific survival as end points.ResultsUC molecular subtypes demonstrate different degrees of immunological responses; the urobasal subtype induces a weak response, the genomically unstable subtype induces an intermediate response, and the squamous cell carcinoma–like subtype induces a strong response. These subtype specific responses are independent of tumor stage and include both TILs and TAMs. The presence of infiltrating CD3⁺ TILs was significantly associated with good prognosis in the MI cases (P<0.01). This positive association was modulated by the presence of CD68⁺ TAMs. The strongest association with poor survival was observed for a high ratio between CD68 and CD3 (P = 7×10^?5).ConclusionUC molecular subtypes induce immunological responses at different levels. A high CD68/CD3 ratio identifies a bad prognosis group among MI UC cases.