Significant Predictors Of Disease Recurrence Research Articles

O-193 Reproductive outcomes in women with Borderline Ovarian Tumours. Does fertility treatment increase the risk of disease recurrence?

Abstract Study question Does fertility treatment (FT) increase the risk of recurrence of Borderline Ovarian Tumours (BOTs)? Summary answer There is a significant association between recurrence of BOTs and exposure to FT (p = 0.025). What is known already The association between pregnancy or controlled ovarian stimulation (COS) and risk of recurrence of BOTs is a controversial topic of interest amongst clinicians and women undergoing treatment. Some studies report a risk of non- invasive relapse following ovarian stimulation between 19.4-23%, whereas earlier case-control studies have shown no significant association.It is important to consider that most studies are limited by their retrospective analysis, with an emphasis on the incidence of primary BOTs following exposure to FT. Whereby, data regarding the risk of disease recurrence following spontaneous pregnancy (SP) or COS specifically, remains sparse. Study design, size, duration A retrospective cohort of women who underwent fertility sparing surgery (FSS) for the management of BOTs between the 1st January 2004 and 31st December 2020 at Imperial College Healthcare NHS Trust, with prospective follow up of reproductive outcomes and recurrence of disease following surgery. Participants/materials, setting, methods Subgroup analysis included a control group of all women not exposed to FT or SP and a non-control group of those who achieved either SP or underwent FT following FSS for the management of BOTs. The recurrence rate of BOTs was determined within each subgroup. Main results and the role of chance 90 women underwent FSS for BOTs. Subgroup analysis confirmed 38.9% (35/90) were in the control group, 50% (45/90) in the non-control and 11.1% (10/90) lost to follow up. In the non-control group, 35.6% (16/45) achieved SP only and 64.4% (29/45) underwent FT. FT included COS for oocyte cryopreservation only (24.4%; 11/45), intracytoplasmic sperm insemination (ICSI) ± fresh or frozen embryo transfer (24.4%; 11/45) and those who underwent COS but also achieved SP without returning to their cryopreserved gametes (15.5%; 7/45). Within the non-control group, 75.6% (34/45) of women conceived, with a livebirth rate per pregnancy of 58.7% (27/46). The recurrence rate in the control and non-control groups were 20% (7/35) and 22.2% (10/45) respectively (p = 0.025) and 24.1% (7/29) following FT. Recurrence rates were 18.8% (3/16) after SP only, 0% (0/11) following oocyte cryopreservation only, 18.2% (2/11) ICSI ± embryo transfer and 71.4% (5/7) in those who underwent COS and achieved a SP. All recurrence of disease presented as serous BOTs. Within the FT group, logistic regression analysis demonstrated no significant predictors of disease recurrence. A combination of SP and FT is significantly associated with recurrence when compared to the following groups: control (p = 0.000), SP only (p = 0.001) and COS only (p = 0.015). Limitations, reasons for caution Due to the partial retrospective nature of the study, certain clinical information was not adequately documented and the subgroups compared were of unequal sample size, whilst overall sample size is also considered low. There was also a lack of control for confounders which may affect disease recurrence. Wider implications of the findings Despite the risk of recurrence of BOTs associated with FT, cases are often non invasive and successfully managed with further FSS with excellent prognosis. This evidence should be used to counsel women of reproductive age to ensure they can fulfil their reproductive aspirations, despite a diagnosis of BOT. Trial registration number NA

Impact of lymph node density on prognosis of advanced laryngeal carcinoma with nodal metastasis

Objective: To determine the prognostic value of lymph node density (LND) as a predictor for tumor recurrence in patients with advanced laryngeal carcinoma undergoing curative surgery. Patients and methods: This is a prospective study, included 87 patients, diagnosed with locally advanced laryngeal carcinoma (T3 & T4a) and carried out total laryngectomy with neck dissection, presented to otorhinolaryngology outpatient clinic at faculty of medicine, Cairo university, Egypt, between June 2018 and May 2019. LND was determined by calculating the ratio between number of resected lymph nodes (LNs) positive for malignancy and total number of resected LNs. The mean follow up duration for tumor recurrence was 24 months (range 17 – 29 months).Results: LND, number of positive LNs, involved surgical margins, presence of metastatic LNs and adjuvant chemoradiation were statistically significant predictors for disease recurrence in univariate analysis. LND was the only independent predictor of recurrence in pathologically positive neck node (pN+) patients in multivariate analysis. In patients with LND > 0.066, hazard ratio for disease recurrence was 3.887 (P=0.021), and for nodal recurrence was 6.453 (P=0.008), reaching LND > 0.25 significantly increased hazard ratio for recurrence to 5.838 (P=0.001), and for nodal recurrence to 9.329 (P=0.001) compared with pN0 cases.Conclusion: LND was found to be the only independent predictor for disease recurrence in pN+ laryngeal cancer. LND should be used complementary to the conventional TNM staging to assess the precise risk of treatment failure and planning of possible postoperative adjuvant treatment.

RET gene mutation analysis and long-term clinical outcomes of medullary thyroid cancer patients.

Medullary thyroid carcinoma is a rare, potentially aggressive tumour, with relatively worse prognosis than well-differentiated thyroid cancer. We evaluated the long-term outcomes and prognosis of medullary thyroid carcinoma patients at a single institution in India and compared outcomes based on results of RET protooncogene mutation analysis. Data were retrieved through a prospectively maintained thyroid cancer database from 1998 to June 2019, and medullary thyroid carcinoma patients were recruited. RET gene mutation status (exon 10-16) was assessed. Patient with a minimum follow-up of 12 months was eligible to be part of the long-term outcome analysis. Out of 149 peripheral blood samples, 42 were positive for RET gene mutation (prevalence of 28.1%). The median follow-up duration was 48 months, ranging from 12 to 240 months. Long-term clinical outcomes of 113 patients were assessed. Two deaths were noted in this series. Both 5- and 10-year survival was cent per cent. Overall survival was 98.2% (97.3% in RET positive and 98.7% in RET negative group). Progression-free survival was 55.4% in total (60% in RET positive and 53.3% in RET negative group). No statistically significant difference was found between RET positive and RET negative groups concerning overall survival (P = 0.6011) and progression-free survival (P = 0.5140). Univariate analysis revealed high calcitonin (>10 pg/mL), stage IV disease, and presence of lymph nodal metastasis to be significant predictors of disease recurrence, however, multivariate analysis demonstrated the presence of lymph node metastases as the only significant predictor of recurrence (P = 0.0005). Medullary thyroid carcinoma patients had relatively favourable long-term outcomes. Long-term survival was similar irrespective of RET mutation status. Presence of lymph node metastases appeared to be the strongest predictor of overall and progression-free survival, followed by Calcitonin level and stage of the disease.

Prognostic Role of Examined and Positive Lymph Nodes after Distal Pancreatectomy for Non-Functioning Neuroendocrine Neoplasms

Background: The most appropriate nodal staging system for non-functioning pancreatic neuroendocrine tumours (NF-PanNETs) remains unclear. Despite some evidence is available for pancreaticoduodenectomy, the adequate nodal staging is still unknown for distal pancreatectomy (DP). The aim of the present study was to evaluate the prognostic impact of the number of positive lymph nodes (PLNs) after DP for NF-PanNETs and to define the minimal number of lymph nodes to be harvested for an appropriate nodal staging. Methods: Data were retrospectively collected from patients who underwent DP with curative intent (R0-R1) for sporadic well-differentiated NF-PanNETs in 4 European high-volume centres. NF-PanNETs with nodal involvement (N+) were subclassified into N1 (1–3 PLNs) and N2 (4 or more PLNs). Univariate and multivariate analyses of disease-free survival (DFS) were performed. Results: Of 271 patients in the study, 62 (23%) had nodal involvement (N+). A higher probability of N+ was associated with the following factors: grading, resection margin status, perineural and microvascular invasion, and the number of examined lymph nodes. Three-year DFS rate for N0, N1, and N2 patients was 92, 72, and 50%, respectively (p < 0.001). At multivariate analysis, independent predictors of DFS were grading, T stage, presence of necrosis, and nodal status. For patients with ≥12 examined/resected lymph nodes, the N status remained a significant predictor of disease recurrence (p < 0.001), while it failed to predict recurrence in patients with <12 lymph nodes examined/resected (p = 0.116). Conclusions: A minimal number of 12 nodes should be harvested in case of DP for NF-PanNET for an appropriate nodal staging. The number of positive lymph nodes is an independent predictor of DFS after DP for NF-PanNET, and the N0/N1/N2 nodal classification seems to be more relevant than the current N0/N+ staging.

Perioperative management of pyoderma gangrenosum

Pyodermagangrenosum (PG) classically presents with an acute inflammatory stage, characterized by rapid evolution of painful ulcerations. The pathergy associated with PG lesions complicates disease management. Although PG is commonly treated with immunosuppression, some patients have refractory noninflammatory ulcers. In this subpopulation, there are case reports of successful surgical treatment. However, there is no consensus on optimal perioperative treatment for patients with PG undergoing surgery of any kind, PG related or otherwise. Therefore, we conducted a comprehensive literature review describing perioperative management practices and risk factors that may predict response to surgical intervention. We identified 126 cases of surgical intervention in patients with active PG; among these, only 16.7% experienced postoperative disease progression. No perioperative treatments or clinical risk factors were identified as statistically significant predictors of disease recurrence. Although limited by case series design and publication bias, this study is a valuable means of hypothesis generation for this rare condition.

A multi-institutional analysis of diffuse large B-cell lymphoma (DLBCL) treated with consolidative radiotherapy and the impact of cell-of-origin on outcomes.

BackgroundPatients with diffuse large B-cell lymphoma (DLBCL) with bulky disease and/or those who fail to achieve complete response benefit from the addition of radiotherapy (RT). We aim to review the outcome, as well as determine the impact of cell-of-origin, on patients undergoing consolidative RT.Patients and methodsPatients with DLBCL treated with radical intent consolidative RT were included. Clinical, pathological and treatment characteristics were extracted from electronic medical records. Survival outcomes and factors that predict for disease-free survival (DFS) were analysed.ResultsSeventy-four patients were included in this analysis. The median follow up was 3 years (0.7–16 years). Fifty-eight percent of patients had stage I–II disease, and 61% received at least 6 cycles of chemotherapy. Cell-of-origin was discernible in 60% of patients, and approximately half were classified as Germinal centre origin. The 5-year overall survival (OS) of this group was excellent at 92% (median survival not reached). The 5-year DFS was 73% (95% CI 57–83%). Seven percent (n = 5) of patients experienced local recurrence at a median time of 6 months. Failure to achieve complete response post RT and/or initial bulky disease are significant predictors of inferior DFS. There was no association between cell-of-origin and DFS or OS.ConclusionsThe outcome of patients who received radiotherapy as consolidation is excellent. Patients who fail to achieve complete response after radiotherapy had poorer outcomes. Despite using radiotherapy, presence of bulky disease remains a significant predictor of disease recurrence. We did not find any association of poorer outcomes, with regards to cell-of-origin, in the use of consolidative RT.

Preoperative neutrophil to lymphocyte ratio improves recurrence prediction of non-muscle invasive bladder cancer

BackgroundThis study aims to prospectively evaluate the ability of Neutrophil-to-Lymphocyte ratio (NLR) to forecast recurrence in patients with non-muscle invasive bladder cancer (NMIBC). This is a continuation of our two previous retrospective studies that indicated the NLR > 2.5 criterion as a predictor of recurrence in patients with NMIBC.MethodsSince December 2013, all patients admitted to our department for TUR-BT and agreed to participate, had a blood drawn for cell count and differential 24 h prior to surgery. Patients with pathological NMIBC were followed prospectively for disease recurrence. The end-point of the follow up was either a cancer recurrence or the termination of the study. Univariate and multivariate Cox regressions were performed to assess the NLR > 2.5 predictive capability for recurrence, versus and in conjunction to the pathologically based EORTC score, among additional statistical analyses.ResultsThe study cohort included 96 men and 17 women with a median age of 72 years. Sixty-four patients (56.6%) have had a recurrence during the study occurring at the median time of 9 months (IQR 6, 13), while the median follow-up time for patients without recurrence was 18 months (IQR 10, 29). Univariate Cox regressions for recurrence demonstrated significance for NLR > 2.5 for the whole cohort (p = 0.011, HR 2.015, CI 1.175–3.454) and for the BCG sub-group (p = 0.023, HR 3.7, CI 1.2–11.9), while the EORTC score demonstrated significance for the ‘No Treatment’ subgroup (p = 0.024, HR 1.278, CI 1.03–1.58). When analyzed together as a multivariate Cox model, the NLR > 2.5 and EORTC score retained their significance for the aforementioned groups, while also improving the EORTC score significance for the whole cohort.ConclusionNLR > 2.5 was found to be a significant predictor of disease recurrence and demonstrated high hazard ratio and worse recurrence-free survival in patients with NMIBC, especially in those treated with BCG. Additionally, our data demonstrated statistical evidence that NLR > 2.5 might have an improving effect on the EORTC score’s prediction when analyzed together.

18F-FDG PET/CT in the detection of asymptomatic malignant melanoma recurrence.

To evaluate the diagnostic accuracy of FDG PET/CT in the detection of asymptomatic recurrence in patients with malignant melanoma who have had resection of their primary lesion. We also aimed to determine the pattern and factors predisposing to disease recurrence. Patients with malignant melanoma who have had surgical resection of their disease and without any clinical evidence of disease recurrence were followed-up with FDG PET/CT. The diagnostic accuracy of FDG PET/CT, pattern of recurrence and factors predictive of disease recurrence were determined. A total of 144 patients were followed-up for a median period of 50.50 months. Asymptomatic recurrence was seen in 37 patients (25.7 %) with a median time to recurrence of 20 months. Lymph node was the commonest site of asymptomatic recurrence. Sex, tumour depth, histology type and presence of nodal metastasis were significant predictors of tumour recurrence. Age, race, site of primary lesion, type of lymph node resection were not significant predictors of disease recurrence. Race has a significant effect on the histological subtype of tumour (nodular maligna was more common in Caucasian while acral lentiginous was more prevalent in the Blacks) and the site of the primary lesion (lower limb in Blacks and trunk in Caucasians). Sensitivity, specificity and accuracy of FDG PET/CT for the detection of disease recurrence were 94.5 %, 87.6 % and 89.6 % respectively. FDG PET/CT is a suitable modality for early detection of asymptomatic recurrence of malignant melanoma. Asymptomatic recurrence most commonly occurs in lymph nodes. Sex, nodal metastasis and tumour pathologic features are predictors of recurrence.

Predicting tumor recurrence in patients with cervical carcinoma treated with definitive chemoradiotherapy: value of quantitative histogram analysis on diffusion-weighted MR images.

Background Further research is required for evaluating the use of ADC histogram analysis in more advanced stages of cervical cancer treated with definitive chemoradiotherapy (CRT). Purpose To investigate the utility of apparent diffusion coefficient (ADC) histogram derived from diffusion-weighted magnetic resonance images in cervical cancer patients treated with definitive CRT. Material and Methods The clinical and radiological data of 50 patients with histologically proven cervical squamous cell carcinoma treated with definitive CRT were retrospectively analyzed. The impact of clinicopathological factors and ADC histogram parameters on prognostic factors and treatment outcomes was assessed. Results The mean and median ADC values for the cohort were 1.043 ± 0.135 × 10-3 mm2/s and 1.018 × 10-3 mm2/s (range, 0.787-1.443 × 10-3 mm2/s). The mean ADC was significantly lower for patients with advanced stage (≥IIB) or lymph node metastasis compared with patients with stage <IIB or no lymph node metastasis. The mean ADC, 75th percentile ADC (ADC75), 90th percentile ADC (ADC90), and 95th percentile ADC (ADC95) were significantly lower in patients with tumor recurrence compared with patients without recurrence. In multivariate analysis, tumor size, ADC75 and ADC95 were independent prognostic factors for both overall survival and disease-free survival. Conclusion ADC histogram parameters could be markers for disease recurrence and for predicting survival outcomes. ADC75, ADC90, and ADC95 of the primary tumor were significant predictors of disease recurrence in cervical cancer patients treated with definitive CRT.

Expression pattern of autophagy-related markers in non-metastatic clear cell renal cell carcinoma: association with disease recurrence following radical nephrectomy.

To evaluate the expression of multiple molecular markers associated with autophagy, a cellular degradation pathway for the clearance of damaged or superfluous proteins and organelles, in clear cell renal cell carcinoma (CCRCC) in order to identify the prognostic significance of these markers in patients undergoing radical nephrectomy. Expression levels of five markers, including autophagy-related gene 5 (Atg5), Atg9, Beclin 1, microtubule-associated protein light chain 3 (LC3), and UNC-51-like kinase 1 (ULK1), in radical nephrectomy specimens from a total of 100 patients with non-metastatic CCRCC were measured by immunohistochemical staining. All the five markers were significantly correlated with some pathological factors reflecting an aggressive phenotype, including the pathological T stage, tumor grade, and microvascular invasion. During the follow-up period of this series (median 58.0 months), disease recurrence developed in 41 of the 100 patients, with a 5-year recurrence-free survival (RFS) rate of 61.3%. On univariate analysis, expression levels of Atg5 and Beclin 1, in addition to the pathological T stage, microvascular invasion, and preoperative CRP level, were identified as significant predictors of disease recurrence. Of these factors, the expression of Beclin 1 and preoperative CRP level were independently correlated with RFS on multivariate analysis. These findings suggest that the combined assessment of expression levels of autophagy-associated markers, particularly Beclin 1, in radical nephrectomy specimens with conventional prognostic parameters, would contribute to the precise prediction of postoperative disease recurrence in patients with non-metastatic CCRCC.

1138 Expression of molecular markers associated with the mammalian target of rapamycin pathway in non-metastatic renal cell carcinoma: Impact on prognostic outcomes following radical nephrectomy

Objectives: To evaluate the expression of multiple molecular markers involved in mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic significance of these markers following radical nephrectomy. Material and methods: The expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic RCC by immunohistochemical staining. Results: During the follow-up period of this series (median, 63.5 mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the C-reactive protein level, pathological stage, and microvascular invasion, were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level, and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor (46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). Conclusions: The combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4EBP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following

Expression of molecular markers associated with the mammalian target of rapamycin pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following radical nephrectomy

ObjectivesTo evaluate the expression of multiple molecular markers involved in mammalian target of rapamycin (mTOR) signaling pathway in renal cell carcinoma (RCC) to determine the prognostic significance of these markers following radical nephrectomy. Material and methodsThe expression levels of 5 markers, including PTEN, phosphorylated (p)-Akt, p-mTOR, p-p70 ribosomal S6 kinase, and p-4E-binding protein 1 (4E-BP1), were measured in radical nephrectomy specimens from 137 patients with nonmetastatic RCC by immunohistochemical staining. ResultsDuring the follow-up period of this series (median, 63.5 mo), disease recurrence occurred in 59 of the 137 patients (43.0%), with a 5-year recurrence-free survival rate of 58.3%. On Univariate analysis, expression levels of p-mTOR and p-4E-BP1, in addition to the C-reactive protein level, pathological stage, and microvascular invasion, were identified as significant predictors for disease recurrence. Of these factors, the expression of p-4E-BP1, C-reactive protein level, and pathological T stage appeared to be independently related to recurrence-free survival on multivariate analysis. Moreover, significant differences were observed in recurrence-free survival according to the positive numbers of these 3 independent factors; that is, disease recurrence developed in 5 of 42 patients with negative results for any risk factor (11.9%), 23 of 50 patients with positive results for a single risk factor (46.0%), and 31 of 45 patients with positive results for 2 or 3 risk factors (68.8%). ConclusionsThe combined evaluation of the expression levels of potential markers in the mTOR signaling pathway, particularly p-4E-BP1, in RCC specimens with conventional prognostic parameters would contribute to the accurate prediction of disease recurrence following radical nephrectomy for nonmetastatic RCC.

Association betweenBRCAMutation Status, Pathological Findings, and Magnetic Resonance Imaging Features in Patients with Breast Cancer at Risk for the Mutation

PurposeWe investigated the relationship between BRCA mutations, pathological findings, and magnetic resonance imaging (MRI) features in patients with breast cancer at risk for the mutation.MethodsGenetic testing for BRCA mutations was performed in 275 breast cancer patients with at least one risk factor for the mutation. Using the breast imaging reporting and data system MR lexicon, morphological and kinetic features were reviewed on MRI scans of 230 tumors in 209 patients. The relationship between BRCA mutations, pathologic findings, and MRI data was examined, and disease recurrence was estimated.ResultsBRCA mutations were detected in 48 patients (23.0%), of which 21 (10.0%) were in BRCA1, and 25 (12.0%) in BRCA2. Additionally, two patients (1.0%) had mutations in both genes. Cancers in patients with BRCA1 mutations more frequently showed a higher nuclear grade (p=0.0041), and triple-negative (TN) phenotype (p<0.0001). On MRI scans, the cancers were seen as mass-type in 182 out of 230 lesions (79.1%), and nonmass type in 48 cases (20.9%). Among the features indentified by MRI, rim enhancement was significantly associated with molecular subtypes based on immunohistochemistry (p<0.0001), and nuclear grade (p=0.0387) in multiple logistic regression analysis. Rim enhancement on MRI, along with advanced pathologic N stage, was associated with increased disease recurrence (p=0.0023) based on multivariate analysis. However, the proportion of mass and nonmass tumors, and the distribution of morphological shape, margin, internal enhancement, and kinetic features assessed by MRI were not different according to BRCA mutation status.ConclusionBRCA1 mutations were associated with aggressive pathological characteristics, and the TN phenotype. Rim enhancement was frequently seen on MRI scans of high-grade cancers and in the TN phenotype. And it was a significant predictor of disease recurrence. However, a direct association with BRCA mutations was not observed.

Prognostic Significance of Rising Serum CA-125 Levels Within the Normal Range in Patients With Epithelial Ovarian, Primary Peritoneal, and Tubal Cancers, Who, After Initial Treatment, Had a Complete Clinical Response

This study aimed to assess the ability of 3 criteria of rising CA-125 levels within the reference range to predict recurrence in patients with ovarian, primary peritoneal, and tubal carcinomas after complete clinical response to initial treatment. Included were patients diagnosed during 1998 to 2008 who fulfilled the following criteria: CA-125 levels of 35 U/mL or greater at diagnosis and recurrence, full primary treatment with a complete clinical and radiographic response, follow-up according to schedule, and at least 2 CA-125 results within the reference range during follow-up. Three criteria of rising CA-125 values within the reference range were used for the prediction of recurrence: (1) an absolute increase of 5 U/mL or higher from the nadir value at completion of chemotherapy, (2) early signal of progressive disease criterion, and (3) a rise to an absolute level of 20 U/mL or greater. Of 82 patients who satisfied study inclusion criteria, 58 (70.7%) had disease recurrence. Early signal of progressive disease and a rise to an absolute level of 20 U/mL or greater were highly statistically significant predictors of disease recurrence (odds ratio, 12.62 [95% confidence interval, 2.71-58.7], P = 0.0012; and odds ratio, 6.7 [95% confidence interval, 2.18-20.54], P = 0.001, respectively) and preceded recurrence by a median of 3 and 3.3 months, respectively. Our data indicate that the early signal of progressive disease criterion and a single rise to an absolute level of 20 U/mL or greater within reference limits are highly predictive of clinical recurrence, although the latter is simpler to use. However, whether this is of practical clinical value remains to be proven.

Expression of epithelial–mesenchymal transition markers in renal cell carcinoma: impact on prognostic outcomes in patients undergoing radical nephrectomy

What's known on the subject? and What does the study add? There have been few studies evaluating the prognostic value of epithelial-mesenchymal transition markers in renal cell carcinoma (RCC); therefore, the significance of these markers in the prognosis of patients with RCC, particularly that in those with localized disease, remains largely unknown. Consideration of the expression levels of potential epithelial-mesenchymal transition markers, particularly clusterin and Twist in addition to conventional prognostic parameters, would contribute to the prediction of disease recurrence after radical nephrectomy for localized renal cell carcinoma. • To evaluate the expression of multiple molecular markers involved in the process of epithelial-mesenchymal transition (EMT) in renal cell carcinoma (RCC) with the aim of clarifying the prognostic significance of these markers in patients undergoing radical nephrectomy. • The expression levels of 11 EMT markers, including E-cadherin, N-cadherin, β-catenin, γ-catenin, clusterin, Slug, Snail, Twist, vimentin, ZEB1 and ZEB2, in radical nephrectomy specimens from 122 patients with clinically localized RCC were measured by immunohistochemical staining. • In this series, disease recurrence occurred in 39 (32.0%) patients, with a 5-year recurrence-free survival rate of 64.4%. • Univariate analysis identified expression levels of E-cadherin, clusterin, Twist and vimentin, in addition to C-reactive protein (CRP) level, pathological stage and microvascular invasion, as significant predictors for disease recurrence. • Of these, expression levels of clusterin and Twist, CRP levels and microvascular invasion appeared to be independently related to disease recurrence on multivariate analysis. • There were significant differences in recurrence-free survival according to positive numbers of these four independent factors: disease recurrence occurred in two of 26 patients negative for any risk factor (7.7%), 23 of 73 patients positive for one or two risk factors (31.5%) and 14 of 23 patients positive for three or four risk factors (60.9%). • Consideration of the expression levels of potential EMT markers, particularly clusterin and Twist, in RCC specimens, in addition to conventional prognostic parameters, contributes to the accurate prediction of disease recurrence after radical nephrectomy for localized RCC.

Impact of age on clinicopathological outcomes and recurrence‐free survival after the surgical management of nonseminomatous germ cell tumour

Study Type - Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The effect of advancing age on the clinicopathological outcomes of men with germ cell testicular cancers remains uncertain. Through the review and comparison of the present large cohort of men with testis cancer, we report on our experience in men aged ≥50 years. Our results showed similar clinical and pathological characteristics, and survival outcomes that compare favourably with those of men aged <50 years. To determine the impact of age on clinicopathological findings and disease recurrence in men with nonseminomatous germ cell tumour (NSGCT) undergoing retroperitoneal lymph node dissection (RPLND). We identified 1246 patients with NSGCT who underwent either primary or post-chemotherapy-RPLND (PC-RPLND) between 1989 and 2006 from our prospective testis cancer database. • Perioperative characteristics were compared among men aged < or ≥50 years. • Multivariable models were used to evaluate the association of age with disease-free survival, controlling for established clinical and pathological features. Of 514 men undergoing primary and 732 men undergoing PC-RPLND, 12 (2.3%) and 23 (3.1%) were aged ≥50 years, respectively. • There were no significant differences between men aged < or ≥50 years for perioperative clinicopathological characteristics, with the exception of pre-RPLND CT nodal size. • The pathological distributions at primary RPLND were similar in men aged < or ≥50 years. After PC-RPLND, there were no differences in RPLND histology, number of lymph nodes resected, estimated blood loss, hospital stay, or perioperative complication rate. • Age at surgery was not a significant predictor of disease recurrence when subjected to a multivariable analysis. Our data suggests that age at RPLND does not predict for disease recurrence and men aged ≥50 years had similar pre- and postoperative characteristics to those aged <50 years. • We conclude that RPLND can be safely performed in men aged ≥50 years and these patients should be offered optimal treatment regimens for NSGCT as directed according to established guidelines.

Significant impact of age at diagnosis on the prognosis of Japanese patients with pT1 renal cell carcinoma following surgical resection

• To retrospectively review oncological outcomes following surgical resection in Japanese patients with pT1 renal cell carcinoma (RCC). • The present study included a total of 832 consecutive Japanese patients who underwent either radical or partial nephrectomy and were subsequently diagnosed as having localized pT1 RCC. • The significance of several clinicopathological factors in their postoperative outcomes was analysed. • The median (range) age of the 832 patients was 66 (31-90) years. Radical and partial nephrectomies were performed for 710 patients (85.3%) and 122 patients (14.7%), respectively. Distribution of pathological stage was pT1a in 582 patients (70.0%) and pT1b in 250 patients (30.0%). • During the observation period (median 44 months, range 3-114 months), postoperative disease recurrence developed in 38 patients (4.6%) and death occurred in 34 (4.1%). The 5-year recurrence-free and overall survival rates were 93.6% and 94.1%, respectively. • Of several factors examined, only age at diagnosis was identified as an independent predictor of both postoperative disease recurrence and overall survival in these patients. Furthermore, there were significant differences in the recurrence-free and overall survivals among patient groups stratified by age at diagnosis. • These findings suggest that age at diagnosis is a significant predictor of disease recurrence as well as overall survival in patients with pT1 RCC following surgical resection; therefore, intensive follow-up of older patients is necessary even for those with pT1 RCC.

1662 EXPRESSION OF POTENTIAL MOLECULAR MARKERS IN RENAL CELL CARCINOMA: IMPACT ON CLINICOPATHOLOGICAL OUTCOMES IN PATIENTS UNDERGOING RADICAL NEPHRECTOMY

INTRODUCTION AND OBJECTIVES: Renal cell carcinoma (RCC) has been shown to be characterized by the unique biological feature as well as the heterogenous genetic background, suggesting the limitations for predicting postoperative outcomes in patients with localized RCC using conventional parameters alone. The objective of this study was to evaluate the expression levels of multiple potential molecular markers in RCC to clarify the significance of these markers as prognostic predictors in patients undergoing radical nephrectomy. METHODS: This study included 153 patients with clinically organ-confined RCC undergoing radical nephrectomy. Expression levels of 12 proteins, including Aurora-A, Bcl-2, Bcl-xL, clusterin, heat shock protein 27 (HSP27), HSP70, HSP90, Ki-67, matrix metalloproteinase (MMP)-2, MMP-9, p53 and vascular endothelial growth factor, in radical nephrectomy specimens obtained from these 153 patients were measured by immunohistochemical staining. RESULTS: Of the 12 markers, clusterin, HSP27, Ki-67, MMP-2 and MMP-9 expression were significantly associated with several conventional prognostic factors. Univariate analysis identified these five markers as significant predictors for disease recurrence as well, while mode of presentation, pathological stage, grade and microvascular invasion were also significant. Of these significant factors, Ki-67 expression, pathological stage and microvascular invasion appeared to be independently related to disease recurrence. Furthermore, there were significant differences in recurrence-free survival according to positive numbers of these three independent factors; that is, disease recurrence occurred in 4 of 56 patients who were negative for risk factor (7.1%), 17 of 71 positive for a single risk factor (23.9%), and 20 of 26 positive for 2 or 3 risk factors (76.9%). CONCLUSIONS: These findings suggest that consideration of expression levels of potential molecular markers in RCC specimens, in addition to conventional prognostic parameters, would contribute to accurate prediction of disease recurrence following radical nephrectomy for localized RCC. Moreover, combined evaluation of Ki-67 expression, pathological stage and microvascular invasion would be particularly useful for further refinement of the system in predicting prognostic outcome following radical nephrectomy for patients with RCC.

Risk factors for recurrence following radical cystectomy for pathologic node negative bladder cancer

To evaluate for risk factors associated with bladder cancer recurrence in patients with pathologically negative lymph nodes. A retrospective review of 405 patients undergoing radical cystectomy for bladder cancer between 1996 and 2008 was performed. Patients with node-positive disease and <6 months of follow up were excluded. Clinical and pathological characteristics including stage, lymphadenectomy type (standard vs. extended), number of nodes removed, margin status, lymphovascular invasion (LVI), perineural invasion (PNI), presence of carcinoma in situ, and site of recurrence were evaluated. Kaplan-Meier analysis was used to calculate 5-year recurrence-free survival stratified by lymph node yield. Two hundred sixty patients met the inclusion criteria. Overall, 80 (30.8%) patients recurred within 5 years. Univariate analysis identified LVI, PNI, extravesical disease, positive margins, and lymph node yield <14 to be significant predictors of disease recurrence. On multivariate analysis LVI, PNI, and node yield <14 retained significance (P = 0.01, 0.037, 0.038, respectively). There was no difference in 5-year recurrence free survival when stratified by node yield using the Kaplan-Meier method (P = 0.138). We identified LVI, PNI, and lymph node yield <14 as three independent risk factors for bladder cancer recurrence in patients with node-negative bladder cancer.

The Total Number of Retroperitoneal Lymph Nodes Resected Impacts Clinical Outcome After Chemotherapy for Metastatic Testicular Cancer

To evaluate the prognostic significance of the total number of lymph nodes obtained at postchemotherapy retroperitoneal lymph node dissection (PC-RPLND). After the multidisciplinary management of metastatic germ cell tumor, approximately 10%-15% of patients with the histologic finding of fibrosis or teratoma will suffer disease recurrence. Between 1989 and 2006, a total of 628 patients underwent PC-RPLND and were found to have either fibrosis or teratoma. After Institutional Review Board approval, complete clinical and pathologic data were obtained from our prospective testis cancer surgical database. A Cox proportional hazards regression model was constructed to evaluate the association of the total number of lymph nodes obtained at PC-RPLND on disease recurrence. On pathologic evaluation, 248 (57%) patients had fibrosis and 184 (43%) patients had teratoma. The median number of lymph nodes resected was 25 (interquartile range, 15-37). On multivariable analysis, increasing postchemotherapy nodal size and decreasing lymph node counts were significant predictors of disease recurrence (P=.01, .04, respectively). For patients with 10 nodes removed, the predicted 2-year relapse free probability was 90%, compared with 97% when 50 nodes were removed. Our data suggest that the total number of lymph nodes removed and analyzed is an independent predictor of disease recurrence after PC-RPLND. This has implications both for the urologist to assure completeness of resection and for the pathologist to meticulously assess the pathologic specimens.