Independent Predictor Of Cancer-specific Survival Research Articles

Evaluation of Preoperative Aspartate Transaminase/Alanine Transaminase Ratio as an Independent Predictive Biomarker in Patients With Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy: APropensity Score Matching Study.

The usefulness of the aspartate transaminase (AST)/alanine transaminase (ALT) ratio (De Ritis ratio) as a predictive biomarker for patients with metastatic renal cell carcinoma (mRCC) undergoing cytoreductive nephrectomy (CN) remains unclear. The data from 118 patients were retrospectively evaluated. The endpoints were cancer-specific survival (CSS) and overall survival (OS) after CN. We compared these according to the AST/ALT ratio before and after 1:1 propensity score matching. The independent predictors for CSS and OS were also analyzed. The area under the receiver operating characteristic curve was 0.603. The maximum Youden index indicated that the cutoff value for the AST/ALT ratio was 1.24. Before matching, a high AST/ALT ratio was significantly associated with inferior CSS and OS (P< .05 for all). After matching, 34 patients each were allocated to the high and low AST/ALT ratio groups. In the matched cohort, CSS and OS tended to be lower in the high AST/ALT ratio group, although the results were not statistically significant (median CSS, 18.4 months vs. not reached, P=.121; OS, 18.4 months vs. not reached, P= .0957). Furthermore, multivariate analyses revealed that the AST/ALT ratio was an independent predictor for CSS and OS (CSS hazard ratio, 2.17, P= .0472; OS hazard ratio, 2.30, P=.0258). The preoperative AST/ALT ratio can be an effective predictive biomarker for CSS and OS in patients with mRCC.

MP22-12 POSTOPERATIVE OUTCOME OF CYSTIC RENAL CELL CARCINOMA DEFINED ON PREOPERATIVE IMAGING: A RETROSPECTIVE STUDY

You have accessJournal of UrologyKidney Cancer: Epidemiology & Evaluation/Staging I1 Apr 2017MP22-12 POSTOPERATIVE OUTCOME OF CYSTIC RENAL CELL CARCINOMA DEFINED ON PREOPERATIVE IMAGING: A RETROSPECTIVE STUDY Taesoo Choi, Jun Phil Na, CHUNG UN LEE, Hyunwoo Chung, SEUNGHEE YUM, Hyun Hwan Sung, Hwang Gyun Jeon, Seong Il Seo, Seong Soo Jeon, Hyun Moo Lee, Han Yong Choi, Chan Kyo Kim, and Byong Chang Jeong Taesoo ChoiTaesoo Choi More articles by this author , Jun Phil NaJun Phil Na More articles by this author , CHUNG UN LEECHUNG UN LEE More articles by this author , Hyunwoo ChungHyunwoo Chung More articles by this author , SEUNGHEE YUMSEUNGHEE YUM More articles by this author , Hyun Hwan SungHyun Hwan Sung More articles by this author , Hwang Gyun JeonHwang Gyun Jeon More articles by this author , Seong Il SeoSeong Il Seo More articles by this author , Seong Soo JeonSeong Soo Jeon More articles by this author , Hyun Moo LeeHyun Moo Lee More articles by this author , Han Yong ChoiHan Yong Choi More articles by this author , Chan Kyo KimChan Kyo Kim More articles by this author , and Byong Chang JeongByong Chang Jeong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.666AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To evaluate postoperative outcome of cystic renal cell carcinoma (RCC) defined on preoperative computed tomography (CT), and to find the optimal cut-off of cystic cystic proportion in association with patients’ prognosis. METHODS In this institutional review board-approved study with waiver of informed consent, a total of 1315 patients who received surgery for single RCC with pre-operative CT were enrolled. The cystic proportion of RCC was determined on CT. The optimal cut-off of cystic proportion was explored regarding cancer-specific survival. The RCCs were categorized as cystic or non-cystic RCCs according to conventional (i.e. cystic proportion = 75%) and the optimal cut-off, and then post-operative outcomes were compared between the two groups. Multivariate Cox regression analysis was performed to determine the independent predictor for cancer-specific survival. RESULTS Of the 1315 lesions, 107 (8.1%) were identified as cystic RCCs according to a conventional cut-off. Postoperative outcome of cystic RCC was significantly better than that of non-cystic RCC (P<0.001). Neither metastasis nor recurrence in patients with cystic RCC was developed after surgery. In association with cancer-specific survival rate, the optimal cut-off of cystic proportion was 45%, and 197 (15.0%) were defined as cystic RCCs accordingly. On Cox regression analysis, cystic proportion = 45% in RCC was an independent predictor of favorable outcome regarding cancer-specific survival (hazard ratio 0.34, P = 0.03). CONCLUSIONS Cystic RCC defined on preoperative CT is associated with low metastatic potential and favorable outcomes after surgery. Particularly, cystic proportion = 45% is an independent prognostic factor for favorable survival. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e261 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Taesoo Choi More articles by this author Jun Phil Na More articles by this author CHUNG UN LEE More articles by this author Hyunwoo Chung More articles by this author SEUNGHEE YUM More articles by this author Hyun Hwan Sung More articles by this author Hwang Gyun Jeon More articles by this author Seong Il Seo More articles by this author Seong Soo Jeon More articles by this author Hyun Moo Lee More articles by this author Han Yong Choi More articles by this author Chan Kyo Kim More articles by this author Byong Chang Jeong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Variant histology as a significant predictor of survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma

ObjectivesTo investigate the effect of variant histology (VH) on survival after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma (UTUC) and the effect of adjuvant chemotherapy on the survival of patients with UTUC with VH. Materials and methodsA total of 452 patients who underwent radical nephroureterectomy for UTUC without neoadjuvant chemotherapy in our institution between 1991 and 2012 were retrospectively analyzed. We performed a comparative analysis between pure UTUC and UTUC with VH groups. The Kaplan-Meier method was used to calculate survival estimates for cancer-specific survival (CSS) and overall survival (OS), and log-rank test was used to conduct comparisons between the groups. Univariate and multivariate Cox-proportional hazard regression analyses were performed to evaluate significant variables associated with CSS and OS. ResultsUTUC with VH was present in 41 (9.1%) patients. UTUC with VH showed aggressive clinicopathological features in comparison with pure UTUC. The Kaplan-Meier curves showed significantly decreased 5-year CSS and OS (both, P<0.001) in UTUC with VH group. Multivariate analysis revealed that VH was an independent predictor of CSS (P<0.001) and OS (P<0.002). The Kaplan-Meier curves also showed significantly decreased 5-year CSS and OS in UTUC with the VH group compared to the pure UTUC group in patients who received adjuvant chemotherapy. ConclusionsWe found that UTUC with VH harbored aggressive biologic features, and VH was an independent prognostic factor for CSS and OS on both univariate and multivariate analyses. In addition, UTUC with VH group had poorer survival outcomes than pure UTUC group in patients who received adjuvant chemotherapy. Consequently, adjuvant treatment modalities other than adjuvant chemotherapy should be considered in this group.

TOP2A, HELLS, ATAD2, and TET3 Are Novel Prognostic Markers in Renal Cell Carcinoma

To identify and validate novel prognostic marker genes in clear cell renal cell carcinoma (RCC) that are increasingly expressed during tumor progression. Total RNA was isolated from normal renal tissue, primary G1 and G3 tumors, 14 samples each, and 32 metastases from RCC patients. Expression profiles were created using oligonucleotide microarrays. Significant gene expression differences (P < .05) were identified among normal kidney, primary tumor, and metastases. For all filtered genes, univariate survival analysis was carried out. Genes for which lower expression was significantly associated with longer survival were further analyzed using multivariate analysis. Expression of the best candidate markers was further validated in an independent cohort of 55 primary tumors using quantitative real-time polymerase chain reaction. Fifty-nine genes exhibited increased expression in primary RCC compared with normal kidney, and in metastases compared with primary tumors. In univariate or multivariate survival analysis, upregulation of 15 genes was significant. Expression of 8 genes was validated by quantitative real-time polymerase chain reaction. Survival analysis in an independent cohort of 55 RCC patients based on expression in primary RCC showed that TOP2A (hazard ratio [HR] = 4.3, P = .005), HELLS (HR = 3.7, P = .007), ATAD2 (HR = 3.7, P = .019), and TET3 (HR = 2.8, P = .035) represent independent predictors for cancer-specific survival. The proteins encoded by these genes function as topoisomerase, helicase, chromatin modifier, and methyl cytosine dioxygenase, respectively. They are involved in proliferation, transcription, and epigenetic modification. High mRNA levels of TOP2A, HELLS, ATAD2, and TET3 are independent predictors of poor outcome in RCC patients and may be used for individual risk-adapted therapy in the future.

Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection.

To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2-6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8-10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3%) had 0-3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

Patient age was an independent predictor of cancer-specific survival in male patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.

We hypothesized that there may be a prognostic difference in age between the genders and evaluated the influence of gender-adjusted age on prognosis in upper tract urothelial carcinoma patients. A total of 839 patients with upper tract urothelial carcinoma from a retrospective multi-institutional cohort were included. The patients were divided into four groups consisting of males (N = 610) and females (N = 229) according to age ((i) <60 years, (ii) 60-69.9 years, (iii) 70-79.9 years and (iv) ≥80 years), and we evaluated the associations of patient age and gender with clinicopathological features and oncological outcomes following radical nephroureterectomy. The median follow-up duration was 34 months. Disease recurrence occurred in 249 patients and 192 patients died of upper tract urothelial carcinoma. The 3-year cancer-specific survival rates were (i) 84.3%, (ii) 80.2%, (iii) 77.1% and (iv) 71.5% in the entire patient population (P = 0.001); (i) 84.5%, (ii) 81.1%, (iii) 76.8% and (iv) 69.7% in males (P = 0.010); and (i) 83.3%, (ii) 76.9%, (iii) 77.7% and (iv) 72.9% in females (P = 0.287), respectively. No significant differences between disease recurrence and age were found in the male or female population. In multivariate analysis, older age was an independent predictor of cancer-specific survival, in addition to advanced pT stage, the presence of lymphovascular invasion and lymph node involvement in males. In contrast, age was not associated with cancer-specific survival in females, while high grade, advanced pT stage, the presence of lymph node involvement and multifocal tumor were independent predictors. The results indicate that gender-adjusted age might be a new prognostic factor in upper tract urothelial carcinoma patients.

Do programmed death 1 (PD-1) and its ligand (PD-L1) play a role in patients with non-clear cell renal cell carcinoma?

Clinical trials targeting programmed death 1 (PD-1) and its ligand PD-L1 (PD-L1) for metastatic renal cell cancer (RCC) are ongoing. The aim of this study is to validate their roles as prognostic markers in non-clear cell (non-cc) RCC. Sixty-four non-cc RCC tissue specimens were collected from patients undergoing renal tumor surgery. Expressions of biomarkers were assessed using immunohistochemistry and compared with clinical characteristics. Survival analyses were performed with a median follow-up of 77.5 (range: 0-176) months. No significant correlations were found for PD-1(+) tumor-infiltrating mononuclear cells (TIMC) or PD-L1(+) expression and clinical attributes in patients with non-cc RCC. Kaplan-Meier analysis revealed no differences in 5- and 10-year cancer-specific survival (CSS) for PD-1(-) TIMC compared to PD-1(+) TIMC (71.4 and 63% versus 72.2 and 61.9%; p=0.88). Intratumoral expression of PD-L1 did not appear to influence the 5- and 10-year CSS significantly, even though a trend was identified (68 and 53.6% versus 80.1 and 75.7%; p=0.08). In multivariate analysis, neither PD-1(+) TIMC nor intratumoral PD-L1(+) expression proved to be independent predictors of CSS (p=0.99 and p=0.68, respectively). Our study demonstrates that PD-1(+) TIMC and intratumoral PD-L1(+) expression did not significantly impact tumor aggressiveness or clinical outcome in non-ccRCC specimens. Due to rare incidence of non-cc RCC in particular according to PD-L1 expression, further analyzes are warranted.

MP03-08 COMPREHENSIVE ANALYSIS AND VALIDATION OF CONTEMPORARY SURVIVAL PROGNOSTICATORS IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH TARGETED THERAPY

You have accessJournal of UrologyKidney Cancer: Advanced (including Drug Therapy) I1 Apr 2016MP03-08 COMPREHENSIVE ANALYSIS AND VALIDATION OF CONTEMPORARY SURVIVAL PROGNOSTICATORS IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA TREATED WITH TARGETED THERAPY Kyo Chul Koo, Kwang Suk Lee, Kang Su Cho, Koon Ho Rha, Sung Joon Hong, Byung Ha Chung, and Dong Hyeon Lee Kyo Chul KooKyo Chul Koo More articles by this author , Kwang Suk LeeKwang Suk Lee More articles by this author , Kang Su ChoKang Su Cho More articles by this author , Koon Ho RhaKoon Ho Rha More articles by this author , Sung Joon HongSung Joon Hong More articles by this author , Byung Ha ChungByung Ha Chung More articles by this author , and Dong Hyeon LeeDong Hyeon Lee More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1901AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In line with the era of targeted-therapy (TT), an increasing number of prognosticators are becoming available for patients with metastatic renal cell carcinoma (mRCC). Here, potential prognosticators of cancer-specific survival (CSS) were identified based on the contemporary literature, and were comprehensively validated in an independent cohort of patients treated for mRCC. METHODS Data were collected from 478 patients treated with TT for mRCC between January 1999 and July 2013 at a single institution. The analysis included 24 clinicopathological covariates that included both traditional and contemporary prognosticators: age, sex, body mass index, Karnofsky performance status (KPS), Charlson Comorbidity Index, anemia, neutrophilia, neutrophil-to-lymphocyte ratio (NLR), thrombocytosis, hypercalcemia, T and N stages, tumor size, grade, subtype, sarcomatoid feature, tumor thrombus, number and location of metastasis, lymph node metastasis (supradiaphragmatic vs. subdiaphragmatic), cytoreductive nephrectomy, time from diagnosis to TT, number of TT lines, and tumor response following TT. Multivariate Cox-regression models were used to quantify the effect of covariates on CSS. RESULTS Median survival from the initial diagnosis of metastasis was 24.5 (IQR 11.5-55.7) months. There were 303 (63.4%) cancer-specific deaths, yielding a 2-year CSS rate of 62.5%. Low KPS, hypercalcemia, NLR, the number of metastatic sites (≥2), and the presence of brain metastases were independent adverse prognosticators of CSS. Patients with at least one adverse prognosticator demonstrated lower 2-year CSS rates compared to those with no prognosticators (53.9% vs. 70.6%; log-rank p<0.001). CONCLUSIONS Together with traditional prognosticators such as KPS and hypercalcemia, the number and location of metastases and NLR were independent predictors of CSS in patients with mRCC treated with TT. Our findings could be useful for guiding clinical decision-making including stratification of patients for TT and inclusion in clinical trials. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e21-e22 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Kyo Chul Koo More articles by this author Kwang Suk Lee More articles by this author Kang Su Cho More articles by this author Koon Ho Rha More articles by this author Sung Joon Hong More articles by this author Byung Ha Chung More articles by this author Dong Hyeon Lee More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD13-12 EXTERNAL VALIDATION OF PROGNOSTIC IMPACT OF PATIENT AGE AND GENDER IN PATIENTS TREATED WITH RADICAL NEPHROURETERECTOMY: PROPOSED NEW PERSPECTIVE OF GENDER-ADJUSTED AGE IN UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I1 Apr 2016PD13-12 EXTERNAL VALIDATION OF PROGNOSTIC IMPACT OF PATIENT AGE AND GENDER IN PATIENTS TREATED WITH RADICAL NEPHROURETERECTOMY: PROPOSED NEW PERSPECTIVE OF GENDER-ADJUSTED AGE IN UPPER TRACT UROTHELIAL CARCINOMA Hiroaki Kobayashi, Eiji Kikuchi, Nobuyuki Tanaka, Suguru Shirotake, Yasumasa Miyazaki, Hiroki Ide, Jun Obata, Katsura Hoshino, Kazuhiro Matsumoto, Gou Kaneko, Masayuki Hagiwara, Takeo Kosaka, Satoshi Hara, Akira Miyajima, Tetsuo Momma, Ken Nakagawa, and Mototsugu Oya Hiroaki KobayashiHiroaki Kobayashi More articles by this author , Eiji KikuchiEiji Kikuchi More articles by this author , Nobuyuki TanakaNobuyuki Tanaka More articles by this author , Suguru ShirotakeSuguru Shirotake More articles by this author , Yasumasa MiyazakiYasumasa Miyazaki More articles by this author , Hiroki IdeHiroki Ide More articles by this author , Jun ObataJun Obata More articles by this author , Katsura HoshinoKatsura Hoshino More articles by this author , Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Gou KanekoGou Kaneko More articles by this author , Masayuki HagiwaraMasayuki Hagiwara More articles by this author , Takeo KosakaTakeo Kosaka More articles by this author , Satoshi HaraSatoshi Hara More articles by this author , Akira MiyajimaAkira Miyajima More articles by this author , Tetsuo MommaTetsuo Momma More articles by this author , Ken NakagawaKen Nakagawa More articles by this author , and Mototsugu OyaMototsugu Oya More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.983AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES It is still controversial whether chronological age at radical nephroureterectomy (RNU) is one of the independent predictors that influence cancer specific survival (CSS) in patients with upper tract urothelial carcinoma (UTUC). When discussing the impact of age on prognosis, there are many differences between the sexes, such as hormonal activity, physiological responses, and carcinogenic exposure. We hypothesized that there may be a prognostic difference in age between males and females and evaluated the influence of gender-adjusted age on prognosis in UTUC patients treated surgically. METHODS A total of 839 patients with UTUC from a retrospective multi-institutional cohort were included. The patients were divided into 4 groups based on chronological age at diagnosis: (1) <60 years, (2) 60-69.9 years, (3) 70-79.9 years, and (4) > 80 years. We then evaluated the associations of patient age and gender with clinicopathological features and oncological outcomes following RNU. The median follow-up duration was 34 months. RESULTS This cohort consisted of 610 (72.7%) males and 229 (27.3%) females, and the numbers of patients in the 4 age groups were (1) 156 (18.6%), (2) 245 (29.2%), (3) 315 (37.5%), and (4) 123 (14.7%), respectively. The median age of this cohort was 70.4 years (IQR: 63-78), and males tended to be younger (median, 68.3 years) than females (median, 71.8 years, p<0.001). Disease recurrence occurred in 249 patients and 192 patients died of UTUC. No significant differences between subsequent disease recurrence and patient age were found in males or females. The 3-year CSS rates of the 4 age groups were (1) 84.3%, (2) 80.2%, (3) 77.1% and (4) 71.5% in the entire patient population (p=0.001), (1) 84.5%, (2) 81.1%, (3) 76.8%, and (4) 69.7% in males (p=0.010), and (1) 83.3%, (2) 76.9%, (3) 77.7%, and (4) 72.9% in females (p=0.287), respectively. In multivariate analysis, older age was an independent predictor of CSS, in addition to advanced pT stage, presence of lynphovascular invasion, and lymph node involvement, in males. To the contrary, age was not associated with CSS in females, while high grade, advanced pT stage, presence of lymph node involvement, and multifocal tumor were independently associated with CSS. CONCLUSIONS Older age, as well as pathological features, was one of the independent prognostic factors for CSS in male patients but not in female patients. The results indicate that gender-adjusted age might be a new prognostic factor in UTUC patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e302 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Hiroaki Kobayashi More articles by this author Eiji Kikuchi More articles by this author Nobuyuki Tanaka More articles by this author Suguru Shirotake More articles by this author Yasumasa Miyazaki More articles by this author Hiroki Ide More articles by this author Jun Obata More articles by this author Katsura Hoshino More articles by this author Kazuhiro Matsumoto More articles by this author Gou Kaneko More articles by this author Masayuki Hagiwara More articles by this author Takeo Kosaka More articles by this author Satoshi Hara More articles by this author Akira Miyajima More articles by this author Tetsuo Momma More articles by this author Ken Nakagawa More articles by this author Mototsugu Oya More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Impact of tumour size on prognosis of upper urinary tract urothelial carcinoma after radical nephroureterectomy: a multi-institutional analysis of 795 cases.

To evaluate the prognostic impact of tumour size on survival outcomes in upper urinary tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Data on 795 patients treated with RNU for UTUC from seven centres were retrospectively analysed with focus on tumour size. Clinicopathological features and relevant prognostic factors were compared between patients with tumours ≤3.0 cm and those with tumours >3.0 cm in size. The primary endpoints were cancer-specific survival (CSS), disease recurrence-free survival (RFS) and overall survival (OS). At a median follow-up of 32 months, 313 (39.4%) patients died from UTUC, 321 (40.4%) developed cancer recurrence, and 359 (45.1%) died from all causes. Tumour size >3.0 cm was associated with unfavourable clinicopathlogical features. Kaplan-Meier analysis showed that tumour size was significantly correlated with worse CSS, RFS and OS (all P < 0.001). Multivariate analysis showed that tumour size was an independent predictor of CSS (hazard ratio [HR] 2.296; P < 0.001), RFS (HR 2.193; P < 0.001) and OS (HR 2.417; P < 0.001). Tumour size >3.0 cm was a significant predictor of CSS, RFS and OS after RNU for patients with UTUC. Further studies are warranted before tumour size is included in risk prediction tools.

Clinical outcomes of anti-androgen withdrawal and subsequent alternative anti-androgen therapy for advanced prostate cancer following failure of initial maximum androgen blockade

The present study aimed to investigate the significance of anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy in patients with advanced prostate cancer (PC) who relapsed after initial maximum androgen blockade (MAB). The present study evaluated the clinical outcomes of 272 consecutive advanced PC patients undergoing anti-androgen withdrawal and/or subsequent alternative anti-androgen therapy with flutamide following the failure of initial MAB using bicalutamide. With the exception of 41 patients (15.1%) who did not undergo anti-androgen withdrawal due to the characteristics of PC suggesting aggressive diseases, prostate-specific antigen (PSA) declined from the baseline value in 83 patients (35.9%), including 18 (7.8%) with PSA decline >50%, but not in the remaining 148 (64.1%). No significant difference in the overall survival (OS) or cancer-specific survival (CSS) among the three groups was observed based on the response to anti-androgen withdrawal. Following the introduction of alternative anti-androgen therapy with flutamide, PSA decline was observed in 185 patients (68.0%), including 103 (37.9%) who achieved a PSA reduction of >50%; however, the PSA level continued to elevate in the remaining 87 (32.0%). Furthermore, of the numerous factors examined, only the duration of the initial MAB therapy was shown to be significantly correlated with the PSA decline following alternative anti-androgen therapy. Multivariate analysis of several factors identified revealed that only PSA decline following alternative anti-androgen therapy was an independent predictor of CSS and OS. If initial MAB is effective, the introduction of alternative anti-androgen therapy may be considered; however, anti-androgen withdrawal should be omitted, irrespective of the characteristics of advanced PC.

Comprehensive analysis and validation of contemporary survival prognosticators in Korean patients with metastatic renal cell carcinoma treated with targeted therapy: prognostic impact of pretreatment neutrophil-to-lymphocyte ratio.

In line with the era of targeted therapy (TT), an increasing number of prognosticators are becoming available for patients with metastatic renal cell carcinoma (mRCC). Here, potential prognosticators of cancer-specific survival (CSS) were identified based on the contemporary literature and were comprehensively validated in an independent cohort of patients treated for mRCC. Data were collected from 478 patients treated with TT for mRCC between January 1999 and July 2013 at a single institution. The analysis included 25 clinicopathological covariates that included both traditional and contemporary prognosticators. Multivariate Cox regression models were used to quantify the effect of covariates on CSS. Median survival from the initial diagnosis of metastasis was 24.5 (IQR, 11.5-55.7) months. There were 303 (63.4%) cancer-specific deaths, yielding a 2-year CSS rate of 62.5%. Low Karnofsky performance status (KPS), hypercalcemia, neutrophil-to-lymphocyte ratio (NLR), the number of metastatic sites (≥2), and the presence of brain metastases were independent adverse prognosticators of CSS. The C-index of the model was 0.78. Patients with at least one adverse prognosticator demonstrated lower 2-year CSS rates compared to those with no prognosticators (53.9 vs. 70.6%; log rank p<0.001). Together with traditional prognosticators such as KPS, hypercalcemia, and the number and location of metastases, the NLR was an independent predictor of CSS in patients with mRCC treated with TT. Our findings could be useful for guiding clinical decision making including stratification of patients for TT and inclusion in clinical trials.

Epidemiology and outcomes of squamous ovarian carcinoma; a population-based study

ObjectiveSquamous ovarian carcinoma (SOC) is a rare tumor. Scarcity of information about the epidemiology and prognosis of SOC hinders attempts at optimal patient management. This retrospective study of a large cohort details the clinicopathological and demographic characteristics and prognosis of women with SOC. MethodsA cohort of patients drawn from the National Cancer Institute's Surveillance Epidemiology and End Results (SEER) database who were diagnosed with SOC between 1988 and 2012 were analyzed. Observed and disease-specific survival was estimated by Kaplan-Meier plots in women who underwent surgery as part of their cancer-related treatment. A Cox hazard regression analysis was performed to determine independent predictors of cancer-specific survival in patients with SOC. ResultsWe identified 341 patients with SOC with a median age at diagnosis of 55years. Stage I, II, III and IV tumors were noted in 34%, 15%, 20.5% and 24.9% of patients, respectively. Five-year cancer-specific survival was 86% for stage I, 54.3% for stage II, 36.3% for stage III and 2.8% for stage IV disease patients. Observed and cancer-specific survival was better for patients that underwent lymphadenectomy (p=0.031). Postoperative radiotherapy was not associated with improved survival. In a multivariate analysis, independent predictors of improved cancer-specific survival were younger age, lower disease stage and lymphadenectomy. ConclusionsSOC is typically a unilateral malignancy with a tendency toward loco-regional spread. Stage I patients have a relatively high survival rate; however, the prognosis is poor for women with abdominal or distant spread. Lymphadenectomy, but not postoperative radiotherapy, is associated with improved survival.

Clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma.

To characterize the site and clinical implications of intravesical recurrence after radical nephroureterectomy for upper urinary tract urothelial carcinoma. Patients who underwent radical nephroureterectomy for upper urinary tract urothelial carcinoma between 2000 and 2011 at 12 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were included in the present study. Those who underwent prior or simultaneous radical cystectomy were excluded. The site of intravesical recurrence was investigated, and the survival curves after radical nephroureterectomy were analyzed retrospectively using the Kaplan-Meier method. Multivariate analyses of factors predicting survival were carried out. A total of 534 patients were eligible for the present study. With a median follow up of 47months, 205 patients (38.4%) had intravesical recurrence. The intravesical recurrence-free survival rates at 1, 2, and 5years were 74.6%, 62.5% and 56.3%, respectively. In a subset of 137 patients with intravesical recurrence who did not have bladder cancer before or at the diagnosis of upper urinary tract urothelial carcinoma, the most frequent site of intravesical recurrence was around the cystotomy (52.6%), followed by at the posterior wall (39.4%) and at the bladder neck (35.8%). A total of 36 patients (17.6%) developed muscle-invasive bladder cancer after radical nephroureterectomy. On multivariate analyses for the subset of patients with non-muscle invasive (≤pT1) upper urinary tract urothelial carcinoma, intravesical recurrence was an independent predictor of cancer-specific survival (HR 4.27, P=0.016) and overall survival (HR 3.00, P=0.018). Most intravesical recurrences occur around the site of bladder mucosal injury within 1year after radical nephroureterectomy, providing important insight into the mechanism of intravesical recurrence. Intravesical recurrence after radical nephroureterectomy had an impact on oncological outcomes of patients with non-muscle invasive upper urinary tract urothelial carcinoma.

Prognostic value of nutritional and hematologic markers in head and neck squamous cell carcinoma treated by chemoradiotherapy

PurposeMalnutrition and systemic lymphopenia are common in many cancers and are associated with tumor progression. The purpose of this study was to investigate the prognostic values of nutritional and hematologic markers in patients with head and neck squamous cell carcinoma (HNSCC). MethodsThis prospective study included 153 patients with treatment-naïve HNSCC who underwent definitive chemoradiotherapy. Body weight, serologic and hematologic parameters were measured at baseline and after 2months of treatment. Univariate and multivariate analyses using Cox proportional hazards model were used to identify predictors of progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS). ResultsBody weight, body mass index (BMI), serum albumin, total serum proteins, hemoglobin, and circulating neutrophil, lymphocyte, monocyte, and platelet counts significantly decreased, but neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) significantly increased after 2months of treatment (P<0.05 each). Multivariate analyses showed that pretreatment hypoalbuminemia and high NLR were independent predictors of PFS (P<0.01 each). ECOG performance status, BMI<18.5kg/m2 and NLR were independent predictors of CSS and OS (P<0.01 each). ConclusionsOur data support the evidence that several nutritional and hematologic markers are associated with the prognosis of HNSCC.

Overexpression of PTP4A3 is associated with metastasis and unfavorable prognosis in bladder cancer.

Bladder cancer (BC) is the most common malignancy in urinary system. The prognosis of metastatic BC is poor, but there remains no reliable marker to early detect metastasis. Dysregulated prenylated protein tyrosine phosphatases (PTPs) are commonly associated with cancer metastasis. From a published BC transcriptome, we identified that PTP IVA3 (PTP4A3) was the most significantly upregulated gene implicated in tumor progression among genes related to prenylated PTPs. We therefore analyzed PTP4A3 expression in our well-characterized cohort of BC. By immunohistochemistry, PTP4A3 expression was determined using H-score. PTP4A3 expression of 295 BCs was compared with clinicopathological parameters, and the effect of PTP4A3 on cancer-specific survival (CSS) and metastasis-free survival (MFS) was also examined. Two independent sets of BCs were used to assess PTP4A3 protein and transcript expression in normal urothelium and different stage tumors. PTP4A3 overexpression was significantly associated with higher pT stage (P<0.001), nodal metastasis (P<0.001), vascular invasion (P<0.001), and perineural invasion (P=0.021). In multivariate analysis, PTP4A3 overexpression was an independent predictor for CSS (P<0.001) and MFS (P=0.007). Notably, the difference in CSS and MFS between high and low PTP4A3-expressing tumors was also significant in muscle-invasive BCs. PTP4A3 protein expression showed significant and stepwise increments from normal urothelium to noninvasive BC, invasive BC, and metastatic foci (P<0.001). PTP4A3 transcript was also obviously upregulated in high-stage BC (P<0.001). PTP4A3 may play a role in BC oncogenesis and is a predictive marker of metastasis. PTP4A3 overexpression represents an independent prognosticator for BC, suggesting its potential theranostic value.

Muscle-invasive bladder cancer is characterized by overexpression of thymidine kinase 1

ObjectiveThymidine kinases have an important role in the synthesis of DNA and exhibit high activity in rapidly proliferating cells. Thymidine kinase 1 (TK1) activity has been shown to be increased in various cancer types and proposed as a prognostic parameter. Aim of the present study was to investigate TK1 in muscle-invasive urothelial carcinoma (UC). MethodsCorresponding UC and benign samples from paraffin embedded tissue of 111 patients treated with cystectomy for invasive UC from 1996 to 2006 were immunohistochemically (IHC) assessed for TK1. IHC expression patterns were evaluated in a semiquantitative fashion by 2 independent reviewers. Localization of staining was categorized into pure nuclear and additional cytoplasmic localization. Uni- and multivariate analyses were performed to assess differential expression in normal and UC tissue and to evaluate the diagnostic and predictive capability of TK1 by correlation to clinical data. To correlate TK1 expression with molecular subtypes of UC, analysis of TK1 RNA expression levels of the Cancer Genome Atlas UC cohort was performed. ResultsTK1 was significantly overexpressed in invasive UC, compared to benign urothelium (P<0.0001), and cytoplasmic expression was more often found in cancer tissue than in benign tissue (P = 0.0001). No correlations of TK1 protein expression patterns to standard histopathological determinants were detected. In univariate analysis, TK1 nuclear and cytoplasmic expression was associated with improved cancer-specific survival (P = 0.0119). However, only metastasis status and histologic grade were identified as independent predictors of cancer-specific survival in multivariate analysis. TK1 expression was merely found in the basal layers of benign urothelium. RNA overexpression of TK1 could be correlated to the biologically more aggressive basal UC subtype. ConclusionsTK1 expression is significantly different in invasive UC and benign urothelium, which underlines its potential as a diagnostic marker. Although TK1 is considered to be a marker of proliferation, and TK1 RNA overexpression is associated with an aggressive UC subtype, its capability as a predictive IHC biomarker for invasive UC remains limited.

Relationship between lymph node ratio and cancer-specific survival in a contemporary series of patients with penile cancer and lymph node metastases

To evaluate the association between lymph node ratio (LNR) and cancer-specific survival (CSS) in a population of patients with penile cancer and lymph node metastases (LNM). We evaluated 81 patients with pathologically determined LNM who were surgically treated at our institution between 2000 and 2012. We considered LNR both as a continuously coded and as a categorically coded variable. The minimum-P-value approach was used to determine the most significant LNR threshold. The Kaplan-Meier method was used to determine CSS rates, and univariable and multivariable Cox regression models were fitted to test the predictors of CSS. The median (interquartile range [IQR]) numbers of positive and removed lymph nodes were 2 (1-4) and 22 (13-30), respectively. The median (IQR) LNR was 10.3 (6.3-16.6)% and the most significant LNR threshold was 22%. The median (IQR) follow-up was 26 (16-62) months. Overall, the 5-year CSS rate was 50.5%. After stratification according to LNR, 5-year CSS rates were 65.2% vs 9.6% in patients with LNR < 22% vs LNR ≥ 22%, respectively (P < 0.001). In multivariable Cox regression models, after adjusting for several established prognostic factors, LNR was as independent predictor of CSS (P≤0.012). Finally, LNR significantly improved the accuracy of multivariable Cox regression models by 4.9-10.5%. Although further investigations are needed to evaluate the relationship between tumour burden and treatment intensity, LNR may represent a powerful predictor of CSS in patients with penile cancer and pathologically determined LNM.

Timing of 1st recurrence affects subsequent clinical outcome in 1st recurrent low grade Ta bladder cancer

before the 1st and 2nd BCG course was present in 42/57 (74%) and 47/ 57 (82%) patients, respectively, diagnosed with UUT and/or urethral carcinoma. Bladder Tis before the 1st and/or 2nd BCG course was the only independent predictor of UUT and/or urethral carcinoma on multivariable analysis. Of the 110 patients, 69 (63%) were alive at last follow-up visit, 18 (16%) have died due to metastatic urothelial carcinoma, and 23 (21%) have died due to other causes. Pattern of disease recurrence within the urinary tract was not an independent predictor of cancer-specific survival. CONCLUSIONS: UUT and/or urethral carcinoma was detected during long-term follow-up in >50% of our patients with high-risk NMIBC “failing” after 2 induction courses of intravesical BCG. The vast majority of these patients had bladder Tis before the 1st and/or 2nd BCG course. Thus, a diagnostic work-up of UUT and prostatic urethra should always be performed in patients experiencing so-called BCG “failure” in order to exclude urothelial carcinoma before additional intravesical therapy or even a radical cystectomy are offered.

Influence of late-stage chronic kidney disease on overall survival in patients with upper tract urothelial carcinoma following radical nephroureterectomy

ObjectivesThe prevalence of both chronic kidney disease (CKD) and upper tract urothelial carcinoma (UTUC) in Taiwan is unusually high, and we aimed to investigate the impact of preoperative renal function on UTUC after radical nephroureterectomy. Materials and methodsBetween 2000 and 2013, 248 UTUC patients were enrolled in this retrospective study after excluding patients who had concomitant muscle-invasive bladder cancer, whose tumor metastasized at initial presentation, and who received perioperative chemotherapy or radiotherapy. The significance of CKD on overall survival (OS), cancer-specific survival (CSS), and bladder recurrence-free survival (BRFS) was evaluated by Cox proportional hazard model. ResultsThe median follow-up time was 45.41 months. Overall 5-year OS, CSS, and BRFS rates were 78.27%, 87.81%, and 70.42%, respectively. Aging, late-stage CKD, and nonorgan-confined primary tumor stage were independent predictors for OS after adjustment. Nonorgan-confined primary tumor stage and lymph node involvement were two independent predictors for CSS after adjustment. Concomitant bladder tumor was the only significant predictor for BRFS after adjustment. ConclusionPatients with late-stage CKD had a higher risk of having poor OS. Patients with concomitant bladder tumor had a greater risk of having bladder cancer recurrence despite primary tumor stage. Concomitant bladder tumor, however, had no effect on OS and CSS in this study.