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We assessed clinical outcomes in patients with metastatic castration-sensitive prostate cancer (mCSPC) treated with two upfront therapies.The medical records of 301 patients with mCSPC treated with androgen deprivation therapy plus upfront abiraterone acetate (ABI) or docetaxel (DOC) between 2014 and 2021 were retrospectively reviewed. Propensity score matching (PSM) was performed to compare survival outcomes. Subgroup analyses of risk factors for second progression were conducted.A total of 95 patients received upfront DOC, whereas 206 received upfront ABI. After PSM, the ABI group had a significantly better castration-resistant prostate cancer (CRPC)-free survival than the DOC group [hazard ratio (HR), 0.53; 95% confidence interval (CI), 0.34-0.82]. Second progression-free survival (PFS2) tended to be longer in the ABI group than in the DOC group, but the difference was not statistically significant (HR, 0.64; 95% CI, 0.33-1.22). No significant difference in overall survival (OS) was found between the two groups (HR, 0.92; 95% CI, 0.42-2.03). In the subgroup analysis, upfront ABI had significantly favorable PFS2 in patients aged ≥ 75 years compared with upfront DOC (p = 0.038). Four risk factors for second progression (primary Gleason 5, liver metastasis, high serum alkaline phosphatase level, and high serum lactate dehydrogenase level) successfully stratified patients into three risk groups.Upfront ABI provided better CRPC-free survival than upfront DOC; however, no significant differences in PFS2 or OS were observed between the two groups. Personalized management based on prognostic risk factors may benefit patients with mCSPC treated with upfront intensified therapies.

Background This retrospective multicenter study aimed to evaluate the survival benefit of upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (RCC) patients stratified by International Metastatic RCC Database Consortium (IMDC) risk criteria. Methods We reviewed the medical records in the Michinoku Database between 2008 and 2019. Patients who received upfront CN, systemic therapy without CN (no CN) and CN after drug therapy (deferred CN) were analyzed. To exclude selection bias due to patient characteristics, baseline clinical data were adjusted by inverse probability of treatment weighting (IPTW). Overall survival (OS) was compared between upfront CN and non-upfront CN (no CN plus deferred CN). Associations between time-varying covariates including systemic therapies and OS stratified by IMDC risk criteria were analyzed by IPTW-adjusted Cox regression method. Results Of 259 patients who fulfilled the selection criteria, 107 were classified in upfront CN and 152 in non-upfront CN group. After IPTW-adjusted analysis, upfront CN showed survival benefit compared to non-upfront CN in patients with IMDC intermediate risk (median OS: 52.5 versus 31.3 months, p p p = 0.03) and in patients with IMDC poor risk (0.26, 0.11–0.59, p Conclusions Upfront CN may confer survival benefit in RCC patients with IMDC intermediate and poor risk.

The aims of this study were to investigate prognosis and validate prognostic models [Memorial Sloan-Kettering Cancer Center (MSKCC), International Metastatic Renal Cell Carcinoma Data Consortium (IMDC), and Japanese metastatic renal cancer (JMRC) models] in the targeted therapy era in Japanese patients with metastatic renal cell carcinoma. We retrospectively analyzed 692 patients who were diagnosed with mRCC from January 2008 to August 2018 in the Michinoku Japan Urological Cancer Study Group database. Nivolumab as sequential therapy was widely used. Other immune checkpoint inhibitors were excluded from this study. The median overall survival (95% confident interval) in all, MSKCC favorable, intermediate, and poor risk patients was 41.0 months (33.9–46.8), not reached (63.5 to not estimable), 46.8 months (37.1–52.9), and 10.4 months (8.9–14.4), respectively. The median overall survival (95% confident interval) in IMDC favorable, intermediate, and poor risk patients was not reached (61.6 to not estimable), 47.4 months (41.4–56.5), and 11.5 (9.9–16.3), respectively. The c-index of the MSKCC, IMDC, and JMRC models calculated at mRCC diagnosis was 0.680, 0.689, and 0.700, respectively. No statistical differences were found in the c-index among the models. While the real-world overall survival in Japanese patients with mRCC in the targeted therapy era improved compared to that previously reported in the cytokine era, there was no clear difference in the survival of poor risk patients between these eras. There were no differences in the superiority among the models.

This study compared real-world outcomes of metastatic renal-cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors or nivolumab plus ipilimumab. Using the International mRCC Database Consortium (IMDC), we retrospectively evaluated intermediate- and poor-risk mRCC patients who were treated with nivolumab plus ipilimumab (Nivo-Ipi), tyrosine kinase inhibitors (TKIs) as the first-line therapy between August 2015 and January 2020. We compared oncological outcomes between the Nivo-Ipi group and TKIs group using multivariate logistic regression analysis with the inverse probability of treatment weighting (IPTW) method. In this study 278 patients were included. There were 52 and 226 patients in the Nivo-Ipi and TKIs groups (sunitinib 97, axitinib 118, sorafenib 9, pazopanib 2), respectively. The median age in the Nivo-Ipi and TKIs groups were 69 and 67 years, respectively. There was no significant difference in age, performance status, history of nephrectomy, and the IMDC risk group distribution between the groups. The objective response rate was significantly higher in the Nivo-Ipi group (38%) than in the TKIs group (23%, P = 0.018). The IPTW-adjusted Cox regression analysis showed that a significantly longer progression-free survival (hazard ratio 0.60, P = 0.039) and overall survival (hazard ratio 0.51, P = 0.037) rates in the Nivo-Ipi group than those in the TKIs group. The oncological outcomes of patients receiving the first-line therapy of nivolumab plus ipilimumab in real-world practice were significantly improved in comparison with first-line TKIs therapy.

Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab’s efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and

This study investigated the clinical impact of carcinoma in situ (CIS) in intravesical Bacillus Calmette-Guérin (BCG) therapy for patients with non-muscle-invasive bladder cancer (NMIBC).This study retrospectively evaluated 3035 patients who were diagnosed with NMIBC and treated by intravesical BCG therapy between 2000 and 2019 at 31 institutions. Patients were divided into six groups according to the presence of CIS as follows: low-grade Ta without concomitant CIS, high-grade Ta without concomitant CIS, high-grade Ta with concomitant CIS, high-grade T1 without concomitant CIS, high-grade T1 with concomitant CIS, and pure CIS (without any papillary lesion). The endpoints were recurrence- and progression-free survival after the initiation of BCG therapy. We analyzed to identify factors associated with recurrence and progression.At a median follow-up of 44.4 months, recurrence and progression were observed in 955 (31.5%) and 316 (10.4%) patients, respectively. Comparison of six groups using univariate and multivariate analysis showed no significant association of CIS. However, CIS in the prostatic urethra was an independent factors associated with progression.Concomitant CIS did not show a significant impact in the analysis of Ta and T1 tumors which were treated using intravesical BCG. Concomitant CIS in the prostatic urethra was associated with high risk of progression. Alternative treatment approaches such as radical cystectomy should be considered for patients with NMIBC who have a risk of progression.

The association between baseline frailty and health-related quality of life (HRQOL) in patients with prostate cancer (PC) remains unknown. We retrospectively evaluated the association of pretreatment frailty with HRQOL in 409 patients with PC from February 2017 to April 2020. Frailty and HRQOL were evaluated using the geriatric 8 (G8) screening tool and QLQ-C30 questionnaire, respectively. The primary objective was comparison of G8 and QOL scores between the localized diseases (M0 group) and metastatic castration-sensitive PC (mCSPC group). Secondary objectives were to study the association of G8 and QOL scores in each group and effect of frailty (G8 ≤ 14) on worse QOL. The median age of patients was 70 years. There were 369 (surgery: 196, radiotherapy: 156, androgen deprivation therapy alone: 17) patients in the M0 and 40 patients in the mCSPC groups. There was a significant difference between the M0 and mCSPC groups in the G8 score (14.5 vs. 12.5), functioning QOL (94 vs. 87), global QOL (75 vs. 58), and 100–symptom QOL (94 vs. 85) scores. G8 scores were significantly associated with functioning, global, and 100–symptom QOL scores in both M0 and mCSPC groups. The multivariable logistic regression analyses showed that frailty (G8 ≤ 14) was significantly associated with worse global QOL, functioning QOL, and 100–symptom QOL scores. The baseline frailty and HRQOL were significantly different between the localized and metastatic disease. The baseline frailty was significantly associated with worse HRQOL in patients with PC.

We investigated the association between the pretreatment quality of life (QOL) and overall survival (OS) in patients with urothelial carcinoma (UC), as the influence of pretreatment QOL on prognosis remains unclear in patients with localized and metastatic UC. Between June 2013 and May 2019, we retrospectively investigated 205 patients with UC who received radical cystectomy or nephroureterectomy for non-metastatic UC (M0 group) or systemic chemotherapy for metastatic UC (M1 group). Patients answered the European Organization for the Research and Treatment of Cancer Quality-of-Life Questionnaire C30 (QLQ-C30) before the treatments. Patients were stratified into two groups: QOL high and low according to the optimal cutoff scores which were defined by receiver operating characteristic curve. Inverse probability of treatment weighting (IPTW)-adjusted multivariate Cox regression analyses were performed to investigate the clinical implication of pretreatment QOL score on OS in patients with UC. The number of patients in the M0 and M1 groups was 125 and 80, respectively. Optimal cutoff values in global, fatigue, pain, appetite loss, physical, and role scores were 33, > 33, > 16

The application of prostate-specific antigen (PSA) in prostate cancer (PC) screening, diagnosis, and prognosis has improved the clinical management of PC patients. However, the PSA assay has been faced with criticism due to its potential association with over-diagnosis and subsequent overtreatment of patients with indolent disease. The United States Preventive Services Task Force incited much debate over PSA-based screening in 2012 by recommending against this approach. However, the PSA assay remains the first-line tool for the early detection of PC. This debate highlights the unmet need for non-invasive PC biomarkers with greater sensitivity and specificity that are capable of distinguishing aggressive disease from indolent disease, predicting treatment response, and guiding treatment decisions. Recent investigations into putative PC biomarkers have focused on PSA isoform assays (prostate health index, 4-kallikurein panel), PC-associated genes in the urine (PCA3 and TMPRSS2-ERG), glycan-associated biomarkers (S2, 3PSA, GCNT1, and tri- and tetra-antennary serum N-glycans), and circulating tumor cells. Although substantial efforts to identify novel PC biomarkers that might replace PSA have been put forth, the majority of the putative PC biomarkers reported in the last few years are still under investigation or validation. This review provides an overview of the current state of PC biomarker research and focuses on a few promising PC biomarkers in development.

There are currently no data supporting carboplatin-based regimens in muscle-invasive bladder cancer patients who are unsuitable for neoadjuvant cisplatin treatment. The aim of this study was to investigate the potential benefit of carboplatin-based regimens in patients with muscle-invasive bladder cancer who were unsuitable for cisplatin. We focused on 171 patients ineligible for cisplatin, including 98 patients who received neoadjuvant gemcitabine and carboplatin (GCarbo) followed by immediate radical cystectomy (GCarbo cohort) and 73 patients who underwent radical cystectomy (RC alone cohort) at Hiroaki University or Aomori Prefectural Hospital. In the neoadjuvant GCarbo cohort, patients underwent two 21-day cycles of GCarbo the two courses of neoadjuvant chemotherapy were followed by radical cystectomy at an interval of 1 month. Of the enrolled patients, 165 (95.3 %) had renal impairment. The median age of the enrolled patients was 71 years, and the median follow-up period was 63 months. The 5-year overall survival rates for the GCarbo and the RC-alone cohorts were 79.5 and 53.8 %, respectively (P

Butyrylcholinesterase (BChE) is an alpha-glycoprotein found in the nervous system and liver. Its serum level is reduced in many clinical conditions, such as liver damage, inflammation, injury, infection, malnutrition, and malignant disease. In this study, we analyzed the potential prognostic significance of preoperative BChE levels in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP). We retrospectively evaluated 535 patients with PCa who underwent RP from 1996−2014 at a single institution. Serum BChE was routinely measured in all patients before operation. Covariates included age, preoperative laboratory data [prostate-specific antigen (PSA), hemoglobin, total protein, albumin, BChE, lactate dehydrogenase, C-reactive protein], clinical T, biopsy Gleason score, D’Amico risk classification, and RP with/without neoadjuvant therapy. Univariate and multivariate analyses were performed to identify clinical factors associated with biochemical recurrence-free survival (BRFS). Univariate analyses were performed using the Kaplan–Meier and log-rank methods, and multivariate analysis was performed using a Cox proportional hazard model. The median BChE level was 255 U/L (normal range 168–470 U/L). The median age of the enrolled patients was 68 years, and the median PSA level at diagnosis of PCa was 8.39 ng/mL. The median follow-up period was 65 months. The 5-year BRFS rate was 72.9 %. The 5-year BRFS rates in the BChE ≥168 and ≤ 167 U/L groups were 77.7 and 55.0 %, respectively (P

Retrospective evaluation of the effectiveness and adverse events (AEs) of a sequential chemotherapy regimen using gemcitabine + carboplatin (GCarbo) followed by GCarbo + docetaxel (GCarboD) for advanced upper-tract urothelial carcinoma (UTUC).We treated 56 patients with advanced UTUC. Mean patient age was 68.9 years, creatinine clearance was 51.2 mL/min, and the observation period was 20 months. Patients received two courses of GCarbo comprising 800 mg/m(2) gemcitabine on days 1, 8, and 15, and carboplatin at an area under the curve of four on day 2. If this regimen was effective, we administered two more courses of GCarbo; if the regimen was ineffective, we switched to two courses of GCarboD (70 mg/m(2)).Complete (n = 3) and partial response (PR; n = 25) were achieved after GCarbo. Mean response duration was 9.7 months. Two of 17 cases achieved PR after GCarboD treatment (mean duration, 31.5 months). Median survival was 14.0 months with the GCarbo/GCarboD regimen. Responders to GCarbo therapy survived significantly longer. AEs with the GCarbo regimen included 31 instances of G3/4 blood toxicity and 8 instances of G3/4 urticaria; however, there were only 6 instances of G3/4 gastrointestinal complications. AEs with the GCarboD regimen included 16 instances of blood toxicity and 8 instances of gastrointestinal complications. Neither regimen resulted in G3/4 renal toxicity.GCarbo and GCarboD chemotherapy may be administered safely to patients with advanced UTUC, with or without renal dysfunction. Response to GCarbo was high (50.0 %) whereas GCarboD was of limited effectiveness for non-responders to GCarbo.

Oncologic benefits of laparoscopic radical nephroureterectomy (LNU) are unclear. We aimed to evaluate the impact of surgical approach for radical nephroureterectomy on oncologic outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC).Of 426 patients who underwent radical nephroureterectomy at five medical centers between February 1995 and February 2017, we retrospectively investigated oncological outcomes in 229 with locally advanced UTUC (stages cT3-4 and/or cN+). The surgical approach was classified as open nephroureterectomy (ONU) or LNU, and oncologic outcomes, including intravesical recurrence-free survival (RFS), visceral RFS, cancer-specific survival (CSS), and overall survival (OS), were compared between the groups. The inverse probability of treatment weighting (IPTW)-adjusted Cox-regression analyses was performed to evaluate the impact of LNU on the prognosis.Of the 229 patients, 48 (21%) underwent LNU. There were significant differences in patient backgrounds, including preoperative renal function, lymph-node involvement, lymphovascular invasion, and surgical margins, between the groups. Before the background adjustment, intravesical RFS, visceral RFS, CSS, and OS were significantly inferior in the ONU group than in the LNU group. However, in the IPTW-adjusted Cox-regression analysis, no significant differences were observed in intravesical RFS (hazard ratio [HR], 0.65; P = 0.476), visceral RFS (HR, 0.46; P = 0.109), CSS (HR, 0.48; P = 0.233), and OS (HR, 0.40; P = 0.147).Surgical approaches were not independently associated with prognosis in patients with locally advanced UTUC.

Clinical benefits of presurgical axitinib therapy for renal cell carcinoma (RCC) extending into the inferior vena cava (IVC) remain unclear. We aimed to investigate surgical benefits and pathological antitumor effects of presurgical axitinib therapy for RCC with IVC thrombus. Of 56 consecutive RCC patients with IVC thrombus between January 1994 and December 2016, 41 patients who underwent radical nephrectomy (RN) were categorized as upfront RN (Upfront group) or presurgical axitinib followed by RN (Presurgical group). We retrospectively evaluated safety, radiologic tumor responses, and Ki-67 proliferation index before and after axitinib administration in the Presurgical group. Surgical outcomes, postoperative complications, and fibrosis within the IVC thrombus were compared between the Upfront and Presurgical groups. The number of patients in the Upfront and Presurgical groups was 31 and 10, respectively. Major presurgical axitinib-related adverse events were grade 2 or 3 hypertension (50%). The median radiological tumor response in the renal tumor, IVC thrombus length, and IVC thrombus volume were −19%, −21 mm, and −54%, respectively. The fibrosis within the IVC thrombus was significantly higher in the Presurgical group (10%) than in the Upfront group (3.4%). The Ki-67 proliferation index was significantly decreased in RN specimens (7.3%) versus needle biopsy specimens (23%) in the Presurgical group. Blood loss and operative duration were significantly lower and shorter, respectively, in the Presurgical group than in the Upfront group. Presurgical axitinib therapy enhanced tumor reduction accompanied by fibrosis and may contribute to surgical risk reduction for selected patients.

The optimal treatment for high-risk prostate cancer (PCa) remains to be established. We previously reported favorable, biochemical recurrence-free survival in high-risk PCa patients treated with a neoadjuvant gonadotropin-releasing hormone agonist or antagonist and estramustine phosphate (EMP) (chemohormonal therapy; CHT) followed by radical prostatectomy (RP). We conducted a retrospective study to elucidate the clinical benefit of neoadjuvant CHT for high-risk PCa patients. We reviewed the clinical and pathological records of 1254 PCa patients who underwent RP and bilateral pelvic lymphadenectomy between July 1996 and April 2016 at Hirosaki University. According to the D’Amico risk classification, we focused on 613 patients in the high-risk group. The high-risk PCa patients were further divided into two groups based on whether the patients received neoadjuvant CHT before RP (EMP group) or not (non-EMP group). The endpoint was overall survival (OS) after surgery. The 5- and 10-year OS rates were 98.5 and 92.6%, respectively. The 10-year OS rate in the EMP group was significantly higher compared to the non-EMP group (P = 0.021). In multivariate analysis, administration of neoadjuvant CHT, lymph node involvement, and castration-resistant PCa status were significantly associated with OS. RP with neoadjuvant CHT using EMP for high-risk PCa patients provided excellent long-term OS.

We evaluated retrospectively the feasibility and effectiveness of carboplatin-based combination chemotherapy in elderly patients with advanced bladder cancer. Forty-seven patients with advanced bladder cancer (33 men and 14 women) and treated at our hospital between August 2004 and December 2011 were enrolled. The average age was 77.1 years (range 70–86 years), the average creatinine clearance was 37.0 ml/min (range 14.5–113.0 ml/min), and the average follow-up period was 17.4 months (range 10–55 months). Twenty-nine patients (61.7 %) were unfit for cisplatin-based chemotherapy. There were 15 recurrent cases after radical surgery and 32 inoperable cases. In this study, the first-line therapy was gemcitabine and carboplatin (GCarbo), with two courses as a set. The second-line therapy was GCarbo and docetaxel (GCarboD) if there was an insufficient response to the first-line therapy. Of the 47 patients who underwent GCarbo therapy, the response rate was 38.3 % (complete response plus partial response), with 5 and 13 patients exhibiting a complete response and a partial response, respectively. The average response duration was 15.7 months (range 2–42 months). The response rate of the nine patients who received GCarboD was 11.1 %, and the overall median survival was 15.0 months. Adverse events occurred in 30 patients (63.8 %) who underwent GCarbo therapy. Bone marrow suppression was observed in 30 patients (61.7 %), and digestive symptoms were observed in three patients (9.0 %). Our study demonstrates that GCarbo is a safe and effective combination chemotherapy in elderly patients with advanced bladder cancer. However, the GCarboD regimen appears to have limited effectiveness for nonresponders to GCarbo therapy.

Although quality of life (QOL) is one of the most important considerations in patients treated with anticancer therapies, desirable regimens for neoadjuvant chemotherapy including QOL in locally advanced urothelial carcinoma remain unclear. The present study evaluated the influence of neoadjuvant platinum-based chemotherapy on QOL in patients with locally advanced urothelial carcinoma. Between June 2013 and March 2016, 83 urothelial carcinoma patients who received two courses of neoadjuvant chemotherapy were enrolled in this prospective observational study. Neoadjuvant regimens included gemcitabine + cisplatin (GCis) or gemcitabine + carboplatin (GCb) therapies. As a primary endpoint, we assessed QOL changes in each group before and after chemotherapy using the Quality of Life questionnaire on days 1, 3, and 15 of each cycle. Secondary endpoints included toxicity, safety, weight loss, renal function decline, and tumor responses. QOL analyses were performed in 39 patients receiving GCis and in 44 patients receiving GCb. Appetite loss, role functioning, nausea/vomiting, physical, and fatigue deteriorated >10% from baseline in the GCis group but not in the GCb group. Constipation worsened, whereas scores for pain and emotional items improved in both groups. Objective response rates were 38.5 and 43.2% in the GCis and GCb groups, respectively. Both GCis and GCb regimens were feasible in terms of QOL. The GCb regimen may be associated with a better QOL status especially in regard to gastrointestinal symptoms.

Neoadjuvant cisplatin-based chemotherapy for patients with muscle-invasive bladder cancer (BC) has better survival benefit than radical cystectomy (RC) alone. However, optimal dosing schedule, including drug selection, number of cycles, and interval between chemotherapy and cystectomy, as well as acceptable regimens remain to be established. We conducted a single-arm prospective study to evaluate efficacy and safety of neoadjuvant gemcitabine plus carboplatin (GCarbo) chemotherapy followed by immediate RC in patients with muscle-invasive BC, including cisplatin-unfit patients.Between March 2005 and June 2011, we enrolled 116 patients with histologically proven muscle-invasive BC, including 44 % of the patients who were identified as cisplatin-unfit. All participants received two courses of GCarbo therapy, gemcitabine 800 mg/m(2) administered on days 1, 8, and 15 and carboplatin with an area under the curve of four (AUC 4) administered on day 2. RC and bilateral pelvic lymphadenectomy were performed approximately within a month after cessation of chemotherapy. The primary endpoint was pT0 in the cystectomy specimen. Secondary endpoints were overall response rate, overall (OS) and disease-free survival (DFS), and toxicity. Survival after cystectomy was analyzed using the Kaplan-Meier method.The RC specimens of 28 (24.1 %) patients showed pT0. At a median follow-up period of 41 months, the OS and DFS rates were 89.7 and 86.3 %, respectively. No patients had grade 3/4 gastrointestinal toxicity or renal impairment.Neoadjuvant GCarbo therapy followed by immediate RC is safe, even in cisplatin-unfit patients, and provides a favorable pathological cancer-free state. The single-arm single-institution study design and relatively short observation period were limitations of this study.

AKR1B10 is considered to contribute to cell proliferation and chemoresistance. In the present study, we examined whether AKR1B10 expression is associated with disease-free survival in bladder cancer patients. We obtained bladder cancer specimens from 10 patients before and after chemotherapy and measured AKR1B10 mRNA levels using real-time PCR. In addition, we conducted an immunohistochemical examination of AKR1B10 expression in 57 patients with bladder cancer before and after chemotherapy. AKR1B10 mRNA expression was significantly higher in the post-chemotherapy group than in the pre-chemotherapy group (p

Complex carbohydrates are major components of the cell membrane and they play crucial roles in cell-cell and cell-extracellular matrix interactions, as well as in signal transduction. They consist of three kinds of molecular species; glycoproteins, proteoglycans, and glycosphingolipids. There is a distinct difference in carbohydrate profiles between normal and tumor tissues. The characteristic carbohydrate expression associated with malignant transformation is caused by "aberrant glycosylation" catalyzed by specific glycosyltransferases and glycosidases. A close relationship between blood type antigens and bladder cancer was first established in the 1960s, using the classic red-cell adherence test. Lectin immunohistochemical staining eventually replaced the red-cell adherence test. In the 1980s, several monoclonal antibodies were raised against complex carbohydrates, and the clinico-pathologic significance of blood type antigens in bladder cancer was investigated using these antibodies. Recent studies have demonstrated the high sensitivity and specificity of immunostaining for Lewis X antigen, a carbohydrate blood type antigen, in exfoliated cells from voided urine samples. Other than blood type antigens, the significance of aberrant glycosylation in bladder cancer has been demonstrated in a number of articles. For instance, overexpression of the ganglioside (an acidic glycosphingolipid which has sialic acid) GM3 induces apoptosis and reduces invasive potential in a bladder cancer cell line. Hyaluronic acid promotes tumor metastasis and is an accurate diagnostic marker for bladder cancer. The expression of N-acetylglucosaminyltransferase V and beta,1-6 branching N-linked oligosaccharides is closely related to low malignant potential in bladder cancer. Selectins and galectins, specific ligands for carbohydrate antigens, are also key molecules involved in the apoptosis and metastasis of cancer cells. Thus, proteoglycans, glycoproteins, and glycosphingolipids, and their ligands, play crucial roles in the malignant transformation, invasion, and metastasis of bladder cancer. A novel diagnostic and therapeutic approach may be possible by taking advantage of innovative techniques in glycobiology.

We investigated the clinical efficacy and the prolongation of survival with combination therapy of estramustine phosphate (EMP) and endocrine therapy in untreated patients with progressive prostate cancer. We randomly divided 57 patients with untreated stage D prostate cancer into two groups, an endocrine monotherapy group and a group receiving combination treatment, consisting of endocrine therapy plus EMP. Treatment was continued until deterioration. There were no significant differences in the improvement rating for subjective/objective symptoms or in progression-free survival between the two groups. However, overall survival was significantly prolonged in the combination therapy group (log-rank test, P = 0.0394; generalized Wilcoxon's test, P = 0.0145). In particular, overall survival was significantly prolonged, compared to that in the endocrine monotherapy group, in patients in the combination therapy group who were less than 74 years old, those with a performance status (PS) of 1 to 3, a pretreatment prostate-specific antigen (PSA) level of more than 20 ng/ml, moderately or poorly differentiated carcinoma, or a partial response (PR) based on the PSA level 12 weeks after the start of treatment. There was no significant difference in the incidence of side effects between the combination therapy and the endocrine monotherapy groups. A combination of EMP with endocrine therapy may be useful for initial treatment in younger patients (aged 73 or younger) and in patients at high risk of progressive prostate cancer.

The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) in high-risk Pca patients treated with a neoadjuvant therapy comprising a luteinizing-hormone-releasing hormone (LHRH) agonist plus low dose estramustine phosphate (EMP) (LHRH+EMP) followed by radical prostatectomy (RP). In the present study, we used a retrospective design via propensity score matching to elucidate the clinical benefit of neoadjuvant LHRH+EMP for high-risk Pca. The Michinoku Urological Cancer Study Group database contained data for 1,268 consecutive Pca patients treated with RP alone at 4 institutions between April 2000 and March 2011 (RP alone group). In the RP alone group, we identified 386 high-risk Pca patients. The neoadjuvant LHRH+EMP group included 274 patients with high-risk Pca treated between September 2005 and November 2013 at Hirosaki University. Neoadjuvant LHRH+EMP therapy included LHRH and EMP administration at a dose of 280 mg/day for 6 months before RP. The outcome measures were overall survival (OS) and BRFS. The propensity score-matched analysis indicated 210 matched pairs from both groups. The 5-year BRFS rates were 90.4 and 65.8 % for the neoadjuvant LHRH+EMP and RP alone groups, respectively (P

Patients with advanced local-stage, high-grade prostate cancer (Pca) and high pretreatment prostate-specific antigen (PSA) levels have inferior outcomes compared to their counterparts with more favorable clinical characteristics. However, some patients exhibit favorable pathological features or experience long-term PSA-free survival after radical prostatectomy (RP). We retrospectively examined the ability of preoperative characteristics to predict pathological and oncological outcomes in high-risk Pca patients who underwent RP. We examined data of 1,268 consecutive Pca patients treated with RP alone at 4 hospitals from the Michinoku Urological Cancer Study Group database. Preoperative predictors included age, PSA level, biopsy Gleason score, clinical T stage, and PSA density (PSAD). The outcome measures pathological T stage and PSA-free survival were evaluated by multivariate analysis. We identified 380 high-risk Pca patients, of which 44 % patients had extracapsular extension. Logistic regression analysis indicated that PSAD was an independent predictor of adverse pathologic stage. The 5-year PSA-free survival rates were 82.9 % for patients with PSAD ≤0.468 ng mL−1 cm−2 and 50.7 % for those with PSAD >0.468 ng mL−1 cm−2 (P

We investigated the biochemical outcome of small-volume prostate cancers [tumor volume (TV)0.5 mL, SVCa] and insignificant prostate cancers (TV0.5 mL without any Gleason pattern 4/5 elements, InsigCa) treated with radical prostatectomy.Between April 2000 and May 2010, 609 patients with prostate cancer underwent radical prostatectomy at Hirosaki University Graduate School of Medicine. Of these, 237 were excluded from the study because of preoperative adjuvant therapy. The remaining 372 patients underwent routine histopathological and TV evaluations. Biochemical recurrence (BCR) was defined as the presence of prostate-specific antigen (PSA) levels greater than 0.2 ng/mL after prostatectomy.The median patient age was 68 years (range 48-78 years) and the median preoperative PSA level was 7.50 ng/mL. The mean follow-up period was 45.9 months and the mean TV was 2.16 mL. Sixty patients (16.3%) had SVCa and 14 (3.7%) had InsigCa. The 5-year BCR-free survival rate for patients with SVCa was 67.3% and that for patients with a TV of 0.5 or greater was 87.1%. A significant difference was seen between the groups using the log-rank test (P = 0.008). We could not identify any BCR in patients with InsigCa.Despite the limited number of cases, patients with InsigCa did not develop BCR whereas 12.9% of those with SVCa developed BCR after radical prostatectomy within 5 years. Accurate prediction of the biochemical outcome of SVCa remains difficult and further studies are needed.

The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC).Sixteen patients with metastatic urothelial cancer, previously treated with a platinum-based regimen, were studied. GC (gemcitabine 750 mg/m(2), on days 1, 8, and 15; carboplatin 200 mg/m(2), on day 2) was administered every 28 days to 15 patients. GDC (gemcitabine 750 mg/m(2), on days 1 and 8; docetaxel 50 mg/m(2), on day 1; carboplatin 200 mg/m(2) on day 1) was administered every 21 days to 9 patients. Eight of the 9 GDC-treated patients had earlier been treated with GC and had become refractory.With the GC therapy, 7 of the 15 treated patients (47%; 95% confidence interval, 21%-73%) showed an objective response, with 3 achieving a clinical complete response (CR) and 4 a partial response (PR). With the GDC therapy, 6 of the 9 treated patients (67%; 95% confidence interval, 29%-92%) showed an objective response, with 1 achieving CR and 5, PR. Five of the 8 (63%) GC-refractory patients responded to GDC therapy. The median duration of response was 4 months (range, 2-10+ months) on GC therapy, and 3 months (range, 3-5 months) on GDC therapy. Toxicities associated with GC were less than those with GDC.GC was effective for refractory metastatic urothelial cancer, and GDC was effective for GC-refractory cancer. The aim of this study was to evaluate the efficacy and safety of two combined chemotherapy regimens in the treatment of previously treated metastatic urothelial carcinoma: gemcitabine plus carboplatin (GC), and gemcitabine, docetaxel, and carboplatin (GDC).

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.

Sarcomatoid renal cell carcinoma (SRCC) is associated with an aggressive course, high incidence of bone metastasis, and an extremely poor prognosis. There are a few case reports concerning the effectiveness of chemotherapy on metastasis in SRCC. To our knowledge, however, there are no reports describing its effectiveness on bone metastasis. We report a 22-year-old woman with an 8-cm x 7-cm left renal mass. Left nephrectomy was done. The pathological diagnosis was SRCC, INF-beta, pT3aN2. Although, she received continuous infusion of interferon alpha-2a (INFalpha-2a) and interleukin-2 (IL-2) as adjuvant therapy, liver metastasis appeared 2 months later. Resection of the liver metastasis was done. After resection of the metastasis, multiple bone metastases appeared, in both humeri, the left chest wall, the left fourth rib, and the left iliac bone. The patient was treated with gemcitabine, 1000 mg/m(2) (days 1, 8), docetaxel 80 mg/m(2) (day 1), and carboplatin 300 mg/m(2) (day 1). A computed tomography (CT) scan after the first cycle revealed that the multiple osteolytic bone tumors had significantly decreased in size. Her ability of daily life (ADL) improved and this continued for almost 2 months. A second course of chemotherapy, with gemcitabine and IL-2 was given, but it was ineffective, and the patient died approximately 16 months after the initial diagnosis of SRCC. Combination chemotherapy with gemcitabine, docetaxel, and carboplatin was effective for the bone metastasis of SRCC.