Clinical nodal staging scores for prostate cancer: a proposal for preoperative risk assessment

Background:

Pelvic lymph node dissection in patients undergoing radical prostatectomy for clinically localised prostate cancer is not without morbidity and its therapeutical benefit is still a matter of debate. The objective of this study was to develop a model that allows preoperative determination of the minimum number of lymph nodes needed to be removed at radical prostatectomy to ensure true nodal status.

Methods:

We analysed data from 4770 patients treated with radical prostatectomy and pelvic lymph node dissection between 2000 and 2011 from eight academic centres. For external validation of our model, we used data from a cohort of 3595 patients who underwent an anatomically defined extended pelvic lymph node dissection. We estimated the sensitivity of pathological nodal staging using a beta-binomial model and developed a novel clinical (preoperative) nodal staging score (cNSS), which represents the probability that a patient has lymph node metastasis as a function of the number of examined nodes.

Results:

In the development and validation cohorts, the probability of missing a positive lymph node decreases with increase in the number of nodes examined. A 90% cNSS can be achieved in the development and validation cohorts by examining 1–6 nodes in cT1 and 6–8 nodes in cT2 tumours. With 11 nodes examined, patients in the development and validation cohorts achieved a cNSS of 90% and 80% with cT3 tumours, respectively.

Conclusions:

Pelvic lymph node dissection is the only reliable technique to ensure accurate nodal staging in patients treated with radical prostatectomy for clinically localised prostate cancer. The minimum number of examined lymph nodes needed for accurate nodal staging may be predictable, being strongly dependent on prostate cancer characteristics at diagnosis.     

Lymph node-positive prostate cancer: current issues,emerging technology and impact on clinical outcome

Lymph node metastasis in patients with prostate cancer indicates a poorer prognosis compared with patients without lymph node metastasis; however, some patients with node-positive disease have long-term survival. Many studies have attempted to discern what characteristics of lymph node metastasis are prognostically significant. These characteristics include nodal tumor volume, number of positive lymph nodes, lymph node density, extranodal extension, lymphovascular invasion and tumor dedifferentiation. Favorable characteristics of regional lymph node involvement included a smaller tumor size and smaller tumor volume. However, the current staging system for prostate cancer does not provide different subclassifications for patients with node-positive prostate cancer. In recent years numerous advanced technologies for the detection of lymph node metastasis have been developed, including molecular imaging techniques and the CellSearch^® Circulating Tumor Cell System. With the increased detection of patients with prostate cancer, emergence of new technology to identify lymph node metastasis and the number of radical prostatectomies being performed on the rise, subclassifying patients with lymph node-positive disease is imperative. Subclassification would provide a better picture of patient prognosis and allow for a better understanding of targeted therapies to treat patients with lymph node metastasis.     

Survival outcomes used to generate version 9 American Joint Committee on Cancer staging system for anal cancer

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including anal cancer, is the standard for cancer staging in the United States. The AJCC staging criteria are dynamic, and periodic updates are conducted to optimize AJCC staging definitions through a panel of experts charged with evaluating new evidence to implement changes. With greater availability of large data sets, the AJCC has since restructured and updated its processes, incorporating prospectively collected data to validate stage group revisions in the version 9 AJCC staging system, including anal cancer. Survival analysis using AJCC eighth edition staging guidelines revealed a lack of hierarchical order in which stage IIIA anal cancer was associated with a better prognosis than stage IIB disease, suggesting that, for anal cancer, tumor (T) category has a greater effect on survival than lymph node (N) category. Accordingly, version 9 stage groups have been appropriately adjusted to reflect contemporary long-term outcomes. This article highlights the changes to the now published AJCC staging system for anal cancer, which: (1) redefined stage IIB as T1–T2N1M0 disease, (2) redefined stage IIIA as T3N0–N1M0 disease, and (3) eliminated stage 0 disease from its guidelines altogether.     

Circulating tumor cells in breast cancer beyond the genotype of primary tumor for tailored therapy

Although TNM staging based on tumor, node lymph status and metastasis status—is the most widely used method in the clinic to classify breast cancer (BC) and assess prognosis, it offers limited information for different BC subgroups. Circulating tumor cells (CTCs) are regarded as minimal residual disease and are proven to have a strong relationship with BC. Detection of ≥5 CTCs per 7.5 mL in peripheral blood predicts poor prognosis in metastatic BC irrespective of other clinical parameters, whereas, in early‐stage BC, detection of CK19⁺ CTCs are also associated with poor prognosis. Increasing data and clinical trials show that CTCs can improve prognostic accuracy and help tailor treatment for patients with BC. However, heterogeneous CTCs in the process of an epithelial‐mesenchymal transition (EMT) in BC makes it a challenge to detect these rare cells. Moreover, the genotypic and phenotypic features of CTCs are different from primary BC tumors. Molecular analysis of CTCs in BC may benefit patients by identifying those amenable to tailored therapy. We propose that CTCs should be used alongside the TNM staging system and the genotype of primary tumor to guide tailored BC diagnosis and treatment.     

Expression of the human cachexia-associated protein (HCAP) in prostate cancer and in a prostate cancer animal model of cachexia

Prostate cancer (CaP) patients with disseminated disease often suffer from severe cachexia, which contributes to mortality in advanced cancer. Human cachexia-associated protein (HCAP) was recently identified from a breast cancer library based on the available 20-amino acid sequence of proteolysis-inducing factor (PIF), which is a highly active cachectic factor isolated from mouse colon adenocarcinoma MAC16. Herein, we investigated the expression of HCAP in CaP and its potential involvement in CaP-associated cachexia. HCAP mRNA was detected in CaP cell lines, in primary CaP tissues and in its osseous metastases. In situ hybridization showed HCAP mRNA to be localized only in the epithelial cells in CaP tissues, in the metastatic foci in bone, liver and lymph node, but not in the stromal cells or in normal prostate tissues. HCAP protein was detected in 9 of 14 CaP metastases but not in normal prostate tissues from cadaveric donors or patients with organ-confined tumors. Our Western blot analysis revealed that HCAP was present in 9 of 19 urine specimens from cachectic CaP patients but not in 19 urine samples of noncachectic patients. HCAP mRNA and protein were also detected in LuCaP 35 and PC-3M xenografts from our cachectic animal models. Our results demonstrated that human CaP cells express HCAP and the expression of HCAP is associated with the progression of CaP and the development of CaP cachexia.     

Proposed modification of the eighth edition of the AJCC-ypTNM staging system of esophageal squamous cell cancer treated with neoadjuvant chemotherapy: Unification of the AJCC staging system and the Japanese classification

BackgroundThe eighth edition of the American Joint Committee on Cancer (AJCC) tumor node metastasis (AJCC-TNM 8th) system adopted the newly separate post-neoadjuvant pathologic stage group (ypTNM). However, it is not compatible with the Japanese pathologic classification after neoadjuvant chemotherapy (JPN-CT-pTNM). The aim of this study is to clarify the subjects of the AJCC-ypTNM 8th and propose a unification of the AJCC and Japanese systems to create novel AJCC-CT-pTNM 8th.MethodsParticipants were 304 esophageal squamous cell carcinoma (ESCC) patients who underwent neoadjuvant chemotherapy followed by 3 stage esophagectomy between 2010 and 2019. Predictive probabilities of pN, pM in AJCC-ypTNM 8th and JPN-CT-pTNM 11th systems were evaluated to propose novel system.ResultsIn training data from 234 patients, the overall survival rate was statistically better for ypStage IIIA than ypStage II (P = 0.040) resulting in staging inversion in AJCC-ypTNM 8th. Predictive probability of pathological N status in AJCC-ypTNM 8th (Akaike Information Criterion: AIC = 979.53) was superior to that in JPN-CT-pTNM 11th (AIC = 999.07). In AJCC-ypTNM 8th, 71% (15/21) of ypM1 diseases were supraclavicular lymph nodes (No. 104 L/N as regional in JPN-CT-pTNM 11th) metastases with considerably good prognosis. The predictive probability of the novel AJCC-CT-pTNM 8th [unification of ypStage II and IIIA, conversion of supraclavicular L/Ns metastases from ypM to ypN] (AIC = 1054.24) was superior to that of the existing AJCC-ypTNM 8th (AIC = 1070.74). The feasibility of novel system was validated using test data from 70 patients.ConclusionsUnification of the AJCC and Japanese systems yields a simpler and more precise predictive system after neoadjuvant chemotherapy.     

Relative prognostic value of TNM7 vs TNM6 in staging oesophageal cancer

Background:

Stage migration consequent upon new cancer staging definitions may result in artifactual alterations in stage-specific survival and prognosis. The aim of this study was to determine the influence of the new TNM7 oesophageal cancer (OC) system on stage categorisation and survival when compared with historical controls.

Methods:

A total of 202 patients diagnosed with operable OC and undergoing oesophagectomy (118 neoadjuvant chemotherapy) were studied. Patients originally classified and staged using TNM6 were retrospectively re-staged using TNM7.

Results:

Re-classification of TNM7 resulted in stage migration in 11.9% of patients (9.9% downstaged, 2.0% upstaged) when compared with TNM6. Five-year survival for stages I, II and III was 78%, 46% and 18% using TNM6, compared with 62%, 51% and 18%, respectively, using TNM7. Univariable analysis revealed that histological grade (P=0.006), pT (P<0.0001), TNM6 pN (P<0.0001), TNM7 pN (P<0.0001), number of lymph node metastases (P<0.0001), TNM6 stage group (P<0.0001), TNM7 stage group (P<0.0001) and TNM7 prognostic group (P<0.0001) were all associated with survival. Multivariable analysis revealed that only the TNM7 prognostic group was independently and significantly associated with survival.

Conclusion:

TNM7 is a better prognostic tool than TNM6 and represents an important advance in staging OC.     

按第七版肺癌T分期和新分级与淋巴结转移关系分析

目的:探讨第7版肺癌T分期和新分级与淋巴结转移的关系.方法:回顾性分析442例行根治性切除及淋巴结清除术的肺癌患者的临床资料、原发肿瘤大小、淋巴结转移情况,运用SPSS软件行数据分析.结果:442例肺癌淋巴结转移率为39.1%,其中肺内淋巴结转移率为17.6%,纵隔淋巴结为7.2%、既有肺内又有纵隔淋巴结转移为14.3%;T1、T2、T3、T4期的淋巴结转移率分别为25.4%、45.3%、41.1%、53.8%,4组间P=0.002.T1与T2、T3、T4间淋巴结转移率比较差别有显著性.T2、T3、T4间两两比较淋巴结转移率无显著差别.N1淋巴结转移例数T1、T2、T3、T4间 P=0.274.N2淋巴结转移例数T1、T2、T3、T4间P=0.001.T1a淋巴结转移率为16.4%,T1b淋巴结转移率为32.0%,两者P=0.043.T2a淋巴结转移率为43.9%,T2b淋巴结转移率为48.1%,P>0.05.结论:第七版肺癌T分期的不同,淋巴结转移率有显著差别,其差别主要在N2上,T1 淋巴结转移率最低.肿瘤大小的分级与淋巴结转移率有关,T1a与T1b比有显著差异,但T2a与T2b间无差别.     

按第七版肺癌T分期和新分级与淋巴结转移关系分析

目的：探讨第7版肺癌T分期和新分级与淋巴结转移的关系。方法：回顾性分析442例行根治性切除及淋巴结清除术的肺癌患者的临床资料、原发肿瘤大小、淋巴结转移情况,运用SPSS软件行数据分析。结果：442例肺癌淋巴结转移率为39.1%,其中肺内淋巴结转移率为17.6%,纵隔淋巴结为7.2%、既有肺内又有纵隔淋巴结转移为14.3%;T1、T2、T3、T4期的淋巴结转移率分别为25.4%、45.3%、41.1%、53.8%,4组间P=0.002。T1与T2、T3、T4间淋巴结转移率比较差别有显著性。T2、T3、T4间两两比较淋巴结转移率无显著差别。N1淋巴结转移例数T1、T2、T3、T4间P=0.274。N2淋巴结转移例数T1、T2、T3、T4间P=0.001。T1a淋巴结转移率为16.4%,T1b淋巴结转移率为32.0%,两者P=0.043。T2a淋巴结转移率为43.9%,T2b淋巴结转移率为48.1%,P〉0.05。结论：第七版肺癌T分期的不同,淋巴结转移率有显著差别,其差别主要在N2上,T1淋巴结转移率最低。肿瘤大小的分级与淋巴结转移率有关,T1a与T1b比有显著差异,但T2a与T2b间无差别。     

Clinical application of nano-carbon to improve the accuracy of lymph node staging in patients with advanced gastric cancer receiving neoadjuvant chemotherapy: a prospective randomized controlled trial

BackgroundThe significance of nano-carbon for lymph node staging in radical gastrectomy for gastric cancer (GC) has been confirmed, but studies on its application for GC patients treated with neoadjuvant chemotherapy (NCT) are rare. The purpose of this study was to explore the clinical value of using carbon nanoparticles suspension injections (CNS) to improve the accuracy of lymph node staging (N staging) of NCT for advanced GC.Methods160 advanced GC patients receiving preoperative NCT were enrolled, according to the random number generated by computer, the enrolled patients were randomly divided into two groups: experimental group (n=80) and control group (n=80). The experimental group received endoscopic injection of CNS within 24 hours prior to NCT, while the control group received this within 24 hours post NCT and before D2 radical resection. SOX [oxaliplatin: 130 mg/(body surface area, BSA): m², first day + S-1: (BSA: <1.25 m², 40 mg each time; ≥1.25 to <1.5 m², 50 mg each time; ≥1.5 m², 60 mg each time), 2 times a day, for 2 weeks] was chosen as the NCT regimen, repeat every 3 weeks, 4 cycles were performed preoperative. Surgery was performed 3 weeks after the end of the 4 cycles of chemotherapy. The staining rate, metastasis rate, metastasis rate of stained lymph nodes, postoperative complication rate, and N staging of the two groups were analyzed and compared.ResultsA total of 3,197 lymph nodes were harvested in the experimental group, including 384 metastatic lymph nodes, 1,424 stained lymph nodes, and 210 metastatic stained lymph nodes. The total number of lymph nodes harvested in the control group was 2,565, including 244 metastatic lymph nodes, 796 stained lymph nodes, and 94 metastatic stained lymph nodes. Compared with the control group, a higher rate of stained lymph nodes, a higher total number of lymph nodes, and an increased number of metastatic lymph nodes were detected in the experimental group.ConclusionsThe application of CNS before NCT in patients with advanced GC can minimize lymph node staging bias after NCT and improve its accuracy.Trial RegistrationChinese Clinical Trial Registry ChiCTR2100047407.     

CT在肺癌临床分期中的应用和评价

为使肺癌得到正确的诊断和治疗，应用新的肺癌国际TNM分期标准是十分重要的。由于CT有助于在肺癌诊断和分期过程中对于原发肿瘤和纵隔淋巴结的评估，同时也有助于搜寻远处转移灶。因此，CT是肺癌最重要的辅助影像检查，而且也可进一步明确观察大气管、大血管、淋巴结及胸膜受侵犯的情况，从而为肺癌的TNM分期提供更有价值的信息和资料。PET-CT的图像融合可使肺癌的定位更加准确，使解剖位置和病灶代谢两者关系更为完善。PET／CT的联合检查和图像融合可改进肺癌的术前TNM分期，可能成为肺癌无创性分期中最为优良的方法。     

TOPK is highly expressed in circulating tumor cells,enabling metastasis of prostate cancer

Circulating tumor cells (CTCs) are important for metastasis in prostate cancer. T-LAK cell-originated protein kinase (TOPK) is highly expressed in cancer cells. Herein, we established a xenograft animal model, isolated and cultured the CTCs, and found CTCs have significantly greater migratory capacity than parental cells. TOPK is more highly expressed in the CTCs than in parental cells and is also highly expressed in the metastatic nodules caused by CTCs in mice. Knocking down TOPK decreased the migration of CTCs both in vitro and in vivo. TOPK was modulated by the PI3K/PTEN and ERK pathways during the metastasis of prostate cancer. High levels of TOPK in the tumors of patients were correlated with advanced stages of prostate cancer, especially for high-risk patients of Gleason score≥8, PSA>20ng/ml. In summary, TOPK was speculated to be one of a potential marker and therapeutic target in advanced prostate cancer.     

Comparison of different lymph node staging systems in prognosis of gastric cancer: a bi-institutional study from Hungary

Objective:The Union for International Cancer Control (UICC) Node (N) classification is the most common used staging method for the prognosis of gastric cancer.It demands adequate,at least 16 lymph nodes (LNs) to be dissected;therefore different staging systems were invented.Methods:Between March 2005 and March 2010,164 patients were evaluated at the Department of General Surgery in the Ken(e)y Gyula Hospital and at the Department of General,Thoracic and Vascular Surgery in the Kaposi Mór Hospital.The 6th,7th and 8th UICC N-staging systems,the number of examined LNs,the number of harvested negative LNs,the metastatic lymph node ratio (MLR) and the log odds of positive LNs (LODDS) were determined to measure their 5-year survival rates and to compare them to each other.Results:The overall 5-year survival rate for all patents was 55.5％ with a median overall survival time of 102 months.The tumor stage,gender,UICC N-stages,MLR and the LODDS were significant prognostic factors for the 5-year survival with univariate analysis.The 6th UICC N-stage did not follow the adequate risk in comparing N2 vs.N0 and N3 vs.N0 with multivariate investigation.Comparison of performances of the residual N classifications proved that the LODDS system was first in the prediction of prognosis during the evaluation of all patents and in cases with less than 16 harvested LNs.The MLR gave the best prognostic prediction when adequate (more than or equal to 16) lymphadenectomy was performed.Conclusions:We suggest the application of LODDS system routinely in western patients and the usage of MLR classification in cases with extended lymphadenectomy.     

Prognostic value of the number and laterality of metastatic inguinal lymph nodes in vulvar cancer: Revisiting the FIGO staging system

Objective

Inguinal lymph node (LN) metastasis is an important prognostic factor in vulvar cancer. Our aims were to analyze the prognostic value of LN metastasis with regard to the number of LNs that were involved and their laterality and compare these results with the current FIGO staging system.

Methods

A retrospective analysis was performed in a series of 234 individuals who underwent inguinal lymphadenectomy for vulvar squamous cell carcinoma from January 1980 to February 2010.

Results

The mean age was 68 years. One hundred seven (45.7%) patients had LN metastasis. Despite the FIGO staging, we did not observe any significant difference in the risk of recurrence or death between patients with 1 positive LN and ≥2 positive LNs. Moreover, there was no difference in outcome between the presence of 1 and 2 positive LNs. On categorizing patients into 3 groups—absence of LN involvement, 1–2 positive LNs, and ≥3 positive LNs—we achieved a significantly better prognostic correlation for progression-free survival, disease-specific survival, and overall survival. Extracapsular spread retained a prognostic role for the risk of recurrence in multivariate analysis. Further, for patients with ≥2 positive LNs, the presence of bilateral positive LNs did not negatively impact the risk of recurrence or death compared with those with unilateral positive LNs.

Conclusions

Our data suggest that the prognostic effect of bilateral LNs reflects the worse prognosis of multiple positive LNs. Regarding prognosis, LN involvement should be categorized into 2 groups—1–2 positive LNs and ≥3 positive LNs.     

Staging for prostate cancer

BACKGROUND: The American Joint Committee on Cancer (AJCC) staging system for prostate cancer is based primarily based on clinical tumor (T) classification. In this article, the authors summarize arguments for incorporating additional pretreatment parameters and creating a new staging system for prostate cancer. METHODS: Men with localized prostate cancer who received treatment with external beam radiation alone were analyzed using the 1997 AJCC staging system compared with a system that included pretreatment prostate-specific antigen (pPSA) level and Gleason score (GS). Multivariate analyses using a Cox proportional-hazards model were carried out to evaluate T classification, GS, and pPSA as predictors of overall survival (OS), disease-specific survival (DSS), and freedom from PSA failure (FFPF). RESULTS.: Based on pretreatment characteristics in a series of contemporary patients, only 0.6% of patients were classified with AJCC stage I disease, 16.0% were classified with AJCC stage III disease, and 83.4% were classified with AJCC stage II disease. Multivariate analyses indicated the independent statistical significance of T classification, GS, and pPSA in predicting OS, DSS, and FFPF (model chi-square value, P < .0001 for each). Using these 3 predictors, subsets of patients who had similar outcomes were combined to provide examples of the insensitivity of the AJCC system for predicting outcomes. Incorporating pPSA and GS allowed the identification of differences in OS, DSS, and FFPF for subsets of patients with AJCC stage II disease (P < .0001, P = .005, and P < .0001, respectively). CONCLUSIONS: The current AJCC staging system does not divide contemporary patients with prostate cancer into prognostic subgroups and does not identify patients who have comparable biochemical control and survival. The AJCC staging system for prostate cancer should be changed to incorporate pPSA, GS, and risk stratification.     

血清白细胞介素18在前列腺癌患者中的临床价值

Objective: To determine serum interleukin-18 (IL-18) levels and their clinical significance in patients with prostate cancer. Methods: Peripheral blood samples were obtained from 38 nonmetastatic and 18 metastatic prostate cancer patients who underwent curative surgery and from 25 healthy volunteers. The serum IL-18 level was determined in each sample with the enzyme-linked immunosorbent assay. Results: The levels of serum IL-18 were increased significantly in prostate cancer patients compared with control subjects (P ＜ 0.05). Serum IL-18 levels were significantly higher in the metastatic patients compared with the nonmetastatic patients (P ＜ 0.01). Patients with bone metastasis had higher serum IL-18 levels compared with patients with liver and lung metastasis (P ＜ 0.01). When the patients were subdivided into groups, it was found that the serum IL-18 levels in patients with T2, T3 and T4 stage were significantly higher than that of T1 stage patients (P ＜ 0.01). Patients with IL-18 levels ≥ 316 pg/mL experienced a significantly lower survival rate compared with the patients who had IL-18levels ＜ 316 pg/mL after undergoing surgery (P ＜ 0.05). The serum IL-18 level was identified as an independent postoperative prognostic factor in multivariate survival analysis using a Cox proportional hazards model (hazard ratio, 4.21; P = 0.02).Conclusion: The serum IL-18 level may be a useful marker in monitoring prostate cancer patients. IL-18 activity in prostate cancer patients with bone metastasis may be more valuable in the follow-up.