A Phase II, Randomized, Open-Label, Multi-arm Study of TAS-115 for Castration-Resistant Prostate Cancer Patients With Bone Metastases.

INTRODUCTION: TAS-115 is an oral multikinase inhibitor targeting the MET proto-oncogene, vascular endothelial growth factor receptor, and colony-stimulating factor 1 receptor. We evaluated the efficacy and safety of TAS-115 in castration-resistant prostate cancer (CRPC) patients with bone metastases. PATIENTS AND METHODS: This phase II study, conducted in Japan, comprised 2 cohorts of CRPC patients. Cohort A included patients with bone metastasis and no history of docetaxel; TAS-115 200 to 400 mg/d was administered with abiraterone and prednisone. Cohort B included patients with symptomatic multiple bone metastases, post- or unfit for docetaxel, randomized 1:1 to receive TAS-115 400 or 600 mg/d orally, once daily, in a repeated weekly schedule of 5 days on/2 days off. The primary endpoint was bone scan index (BSI) response rate at Week 12 in each dose group. RESULTS: Cohorts A and B included 24 and 26 patients, respectively. The 12-week BSI response rates for 200, 300, and 400 mg were 0%, 33.3%, and 16.7% in Cohort A, and for 400 and 600 mg were 7.1% and 25.0% in Cohort B. The best BSI response rates for 200, 300, and 400 mg were 0%, 66.7%, and 16.7% in Cohort A, and for 400 and 600 mg were 7.1% and 33.3% in Cohort B. A ≥ 30% reduction in BPI-SF score was shown in 57.7% of patients in Cohort B. The most frequent Grade ≥ 3 adverse drug reactions were hypophosphatemia (20.8%) in Cohort A and anemia (23.1%) in Cohort B. CONCLUSION: TAS-115 appears to demonstrate anti-tumor activity and acceptable tolerability in CRPC patients with bone metastases.

Oncologic outcomes of laparoscopic radical nephroureterectomy in conjunction with template-based lymph node dissection: An extended follow-up study.

OBJECTIVES: This study investigated the relapse pattern and oncologic outcomes after laparoscopic nephroureterectomy with template-based lymph node dissection (LND) in patients with clinically node-negative (cN0) upper urinary tract urothelial carcinoma. The frequency of lymph node metastasis, including micrometastases, was also evaluated. METHODS AND MATERIALS: A total of 105 patients with cTa-3N0M0 upper urinary tract urothelial carcinoma were analyzed, all of whom underwent regional LND during laparoscopic nephroureterectomy. Of those patients, 96 (91%) underwent complete LND in accordance with an anatomical template-based rule. We collected patient characteristics, pathological data, and follow-up data from medical charts. Micrometastases were assessed by pan-cytokeratin immunohistochemistry. Nonurothelial recurrence-free survival and cancer-specific survival were estimated using the Kaplan-Meier method. RESULTS: The median number of lymph nodes removed was 12 (range, 1-59). Lymph node metastasis was identified by routine pathological examination in 7 (7/105, 6.7%) patients. Pan-cytokeratin immunohistochemistry revealed micrometastases in 5 additional patients (pNmicro +: 5/105, 4.8%). Nonurothelial disease recurrence was observed in 21 (20%) patients at a median of 10 months (range: 1-33) after surgery. Distant metastasis was dominant (15/105, 14.3%), followed by locoregional recurrence (5/105, 4.8%) and both (1/105, 0.95%). The 5-year nonurothelial recurrence-free survival rates were 84.8% for pN0, 53.3% for pNmicro+, and 19.1% for pN+ (3-sample log-rank test, P < 0.0001). The 5-year cancer-specific survival rates were 95.0% for pN0, 53.3% for pNmicro+, and 23.8% for pN+ (P < 0.0001). CONCLUSIONS: Our observation showed that template-based LND could contribute to precise disease staging and better local disease control probably by eliminating nodal disease, compared with previous studies. The survival impact and ideal management of pNmicro+ disease should be evaluated in a larger cohort.

Possibility for Dose Optimization of Pazopanib from Its Plasma Concentration in Japanese Patients with Cancer.

The currently approved dose of pazopanib (800 mg) is being re-examined owing to its adverse effects. The aim of this study was to evaluate the relationships among starting or maintenance doses of pazopanib, estimated pazopanib Cmin, and other clinical factors, including albumin and α-1 acid glycoprotein levels, in soft-tissue sarcoma and renal cell carcinoma. We also determined whether therapeutic drug monitoring of pazopanib concentrations may be used to improve its therapeutic efficacy and prevent adverse effects. Forty patients who received pazopanib for renal cancer or soft-tissue sarcoma at the Hokkaido Cancer Center were evaluated prospectively. Cmin for pazopanib was calculated based on the measured values from the plasma samples. The efficacy and time to treatment failure were then assessed. The pazopanib maintenance doses were 200 (n = 4), 400 (n = 34), 600 (n = 4), and 800 mg (n = 1). Most patients (65%) who received a 400 mg dose had an effective pazopanib concentration (≧20 µg/mL), whereas 35% of patients who received the 400 mg dose had ineffective concentrations (<20 µg/mL). Logistic regression analysis revealed that only the albumin level was significantly associated with effective pazopanib concentrations (odds ratio: 1.37, p = 0.0234). In conclusion, a dose of 400 mg had been effective and well tolerated in more than half of patients in this study. However, therapeutic drug monitoring is necessary during pazopanib therapy.

A randomized, double-blind, comparison of radium-223 and placebo, in combination with abiraterone acetate and prednisolone, in castration-resistant metastatic prostate cancer: subgroup analysis of Japanese patients in the ERA 223 study.

BACKGROUND: ERA 223 compared concurrent abiraterone acetate/prednisolone (AAP) plus radium-223 with AAP plus placebo in men with chemotherapy-naïve asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) and bone metastases. We report data from a subgroup of Japanese patients in ERA 223. METHODS: Patients were randomized to radium-223 (55 kBq/kg) or placebo once every 4 weeks (max. 6 cycles), and also received oral abiraterone acetate 1000 mg once daily plus prednisone/prednisolone 5 mg twice daily during and after radium-223/placebo treatment, until a symptomatic skeletal event (SSE). The primary endpoint was SSE-free survival (SSE-FS); overall survival (OS) was a secondary endpoint. RESULTS: Of 806 patients randomized in ERA 223, 114 patients (57 per arm) were enrolled in Japan. SSE-FS was not improved significantly in the radium-223 arm [25.5 months, 95% CI 20.6-not estimated (NE)] compared with the placebo arm (28.7 months, 95% CI 19.7-NE) (HR = 0.907, 95% CI 0.501-1.642). OS and other secondary endpoints were not improved significantly in the radium-223 arm. The incidence of fracture was 23% and 11% in the radium-223 and placebo arms, respectively. The incidence of death was 32% and 36%, respectively. CONCLUSIONS: In the Japanese ERA 223 subgroup, concurrent treatment with AAP and radium-223 did not significantly improve SSE-FS and increased the incidence of fracture, similar to outcomes achieved in the overall population, while an increased incidence of death was not evident. The combination of radium-223 with AAP is not recommended in Japanese patients with asymptomatic or mildly symptomatic mCRPC and bone metastases. CLINICAL TRIAL REGISTRATION: Clinical trial registration no: NCT02043678.

Phase I trial of TAK-385 in hormone treatment-naïve Japanese patients with nonmetastatic prostate cancer.

This open-label, phase I dose-finding study evaluated the gonadotropin-releasing hormone antagonist, TAK-385, in Japanese patients with nonmetastatic prostate cancer. In a two-part design, patients received daily oral TAK-385 at doses of 320 (loading, day 1)/80 (maintenance, day 2 and thereafter), 320/120, 320/160, or 360/120 mg for 28 days in a dose-escalation phase (part A, n = 13), and at 320/80 or 320/120 mg for up to 96 weeks in a randomized expansion phase (part B, n = 30). Primary endpoint in both parts was safety, including dose-limiting toxicity in part A. Secondary endpoints included pharmacokinetics, pharmacodynamics, and prostate-specific antigen concentration. Ten (77%) patients in part A and all patients in part B experienced an adverse event; hot flush (part A, n = 4; part B, n = 15), viral upper respiratory tract infection (part A, n = 1; part B, n = 10), and diarrhea (part B, n = 8) were most frequent. No dose-limiting toxicities were observed (part A). In 12 evaluable patients (part A), TAK-385 was rapidly absorbed after a single loading dose; on day 28 (maintenance dose), median steady-state Tmax was ~1-2 hours and mean t1/2z was 67-79 hours. All doses rapidly reduced testosterone concentrations to castration levels within 1 week. Durable reductions in prostate-specific antigen of >90% from baseline were observed through 96 weeks. TAK-385 appeared tolerable and resulted in sustained reductions in testosterone to castration levels at all doses. The lowest loading/maintenance dose required for a clinical effect was 320/80 mg. ClinicalTrials.gov: NCT02141659.

Axitinib-Induced Hypothyroidism as a Predictor of Long-Term Survival in Patients with Metastatic Renal Cell Carcinoma.

BACKGROUND: The side effects of sunitinib, namely onset of hypertension and hypothyroidism, have been reported to be predictive biomarkers of treatment efficacy. However, the relationship between hypothyroidism and prolongation of survival in treatment with axitinib, a drug similar to sunitinib, has not yet been reported. OBJECTIVE: In this study, we examined the relationship between the onset of hypothyroidism caused by axitinib and overall survival (OS) and progression-free survival (PFS). METHODS: In this retrospective study, 44 Japanese patients, including 30 men and 14 women, were enrolled. The average age of subjects in this study was 67 years. RESULTS: During treatment, 68% of patients developed hypothyroidism, with an average peak thyroid-stimulating hormone (TSH) value of 15.7 mIU/L. Patients with TSH > 4 mIU/L and required thyroid hormone regulation with levothyroxine had prolonged PFS (11.1 vs. 3.5 months; p = 0.002) and OS (26.4 vs. 15.6 months; p = 0.02). Hypothyroidism was found to be a significant side effect of axitinib in patients with metastatic renal cell carcinoma (mRCC). Patients with hypothyroidism had significantly longer PFS and OS. CONCLUSION: Our findings indicate that hypothyroidism may be a predictive marker of therapeutic effect of axitinib against mRCC.

Comparative study of lymph node dissection, and oncological outcomes of laparoscopic and open radical nephroureterectomy for patients with urothelial carcinoma of the upper urinary tract undergoing regional lymph node dissection.

OBJECTIVE: To assess the number of lymph nodes removed as a surrogate marker of the extent of lymph node dissection, and compare survival outcomes between laparoscopic radical nephroureterectomy (LRNU) and open radical nephroureterectomy (ORNU) in patients undergoing standardized lymph node dissection. METHODS: We retrospectively analyzed the data of 214 cTanyN0M0 patients undergoing radical NU with regional lymph node dissection according to the tumor location. The Kaplan-Meier method and Cox hazards model were utilized for survival analyses, including recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: A total of 114 patients underwent LRNU and 100 underwent ORNU. There was no significant difference in the pT stage, pN stage, or tumor grade, but distal ureteral tumors were more frequent in the LRNU group. The number of lymph nodes removed did not differ between the two groups [LRNU: 12 (median), ORNU: 11.5, P = 0.3852]. Lymph node metastasis was pathologically identified in 19 patients (8.9%). The 5-year RFS (ORNU: 71.7%, LRNU: 74%, P = 0.7829), CSS (77.8 and, 80%, P = 0.8441) and OS (72.8, and 75.9%, P = 0.3456) did not differ between the two groups. In the sub-analysis of pT3/4 patients (n = 83), there were no significant differences in RFS, CSS, or OS between the two groups, although Kaplan-Meier survival curves were slightly better for those receiving ORNU. In the multivariate model, LRNU was not significantly correlated with a poorer RFS, CSS or OS. CONCLUSION: Our data support the feasibility of lymph node dissection with a laparoscopic approach and the equivalent oncological outcome of LRNU compared with ORNU when regional lymph node dissection is performed. However, LRNU should be performed after careful patient selection for advanced disease.

The usefulness of testosterone administration in identifying false-positive elevation of serum human chorionic gonadotropin in patients with germ cell tumor.

OBJECTIVE: The pituitary production of human chorionic gonadotropin (hCG) can cause false-positive results during or after germ cell tumor (GCT) treatment. Because hypogonadism leads to pituitary hCG production, testosterone administration test (TAT) has been recommended for pituitary hCG diagnosis. However, little is known about its efficacy for the discrimination of pituitary hCG as detected by currently used hCG assays in treatment of GCT. We conducted a retrospective multicenter study to determine the usefulness of TAT. MATERIALS AND METHODS: The study included 60 patients who underwent TAT for the discrimination of pituitary hCG. In principle, serum hCG levels were measured 1 week after testosterone enanthate administration (250 mg). When the serum hCG levels decreased below the normal upper range, the results of TAT were determined positive. In this case, the elevated hCG was considered to be derived from pituitary and not from GCT. RESULTS: Serum hCG levels were normalized after TAT in 36 of 60 patients (60%). Before TAT, the hCG levels were below 1.0 IU/L in 13 patients (36%), 1.0-1.9 IU/L in 11 (31%), 2.0-2.9 IU/L in 7 (19%), and >3.0 IU/L in 5 (14%) of TAT-positive patients. Of them, 28 (78%) patients were successfully managed without further treatment with chemotherapy after TAT. Pituitary hCG was associated with higher levels of LH and not necessarily associated with low levels of testosterone. CONCLUSION: Determining the TAT status of patients was effective in discriminating pituitary hCG production.

[Comparison of the Four-Week and Three-Week Regimens of GC Therapy for Urothelial Cancer].

Although GC therapy (the traditional 4-week[4W]regimen)is administered to urothelial cancer patients, discontinuation of gemcitabine after 15 days of administration is a problem. One solution is to use a 3-week (3W) regimen. Because a Japanese study comparing the 3W to the 4W regimens reported the lower efficacy and safety of the 3W regimen, we compared these regimens in a retrospective study. Leukopenia of Grade≥occurred in 18% and 18% of cases and anemia of Grade≥3 occurred in 28% and 39% of cases treated with the 3W and 4W regimens, respectively. On the other hand, thrombocytopenia of Grade≥3 occurred in 13% and 39% of cases treated with the 3W and 4W regimens, respectively (p< 0.001). In addition, overall survival was 14.8 months and 15.0 months for the 3W and 4W regimens, respectively (p=0.97). Thus, the 3W regimen as an alternative treatment instead of the 4W regimen is considered a highly tolerated regimen.

Voided urine cytology and low-grade urothelial neoplasia of the bladder: factors that influence the sensitivity.

INTRODUCTION: The aims of this study were to show the 10-year results of voided urine cytology (VUC) performed using liquid-based cytology (LBC) with CytoRich Red and to discuss the factors that influence the sensitivity of low-grade urothelial neoplasia (LGUN) of the urinary bladder. MATERIALS AND METHOD: We calculated the sensitivity of VUC in 421 histologically confirmed cases included in the pathology database of Hokkaido Cancer Center in Japan and studied various factors influencing sensitivity. RESULTS: The cumulative sensitivity of VUC was 95.8% in 143 cases of primary high-grade urothelial carcinomas, compared with 59.5% in 74 cases of LGUN. These findings were only slightly different from the previous results of Koss et al. The sensitivity in LGUN, however, showed lower values in some conditions, including in secondary cases, with a lower frequency of examinations and smaller tumor volumes. LBC preparations allowed us to observe a greater number of tumor cells and cell clusters than conventional methods in LGUN cases. CONCLUSIONS: The sensitivity of VUC can be improved by increasing the frequency of examinations and adopting a valid preparation method in order to augment the number of cells and cell clusters on individual glass slides. LBC preparations may allow cytopathologists to obtain a better sense for and understanding of the cytologic findings of LGUN.

Prospective mapping of lymph node metastasis in Japanese patients undergoing radical cystectomy for bladder cancer: characteristics of micrometastasis.

OBJECTIVE: To investigate node-disease prevalence including micrometastases and its survival impact on bladder cancer patients. METHODS: A total of 60 patients participated in this study, in which extended lymph node dissection was carried out according to the prospective rule (below aortic bifurcation). Radical cystectomy and extended lymph node dissection were performed by open surgery (n = 23) or laparoscopically (n = 37). Perioperative, pathological and follow-up data were collected. Micrometastasis in lymph nodes was investigated by pan-cytokeratin immunohistochemistry. Recurrence-free survival was estimated with the Kaplan-Meier method. RESULTS: The median number of lymph nodes removed was 29 (range: 10-103) and there was no significant difference between the two groups (open group: median 30, laparoscopic group: median 29). Routine pathological examination revealed that 10 patients had lymph node metastases. Immunohistochemistry revealed micrometastases in four additional patients (pNmicro+), who had been diagnosed with pN0 on routine pathological examination. After excluding the three patients with pure nonurothelial carcinoma on the final pathology (small cell carcinoma: n = 2, adenocarcinoma: n = 1), 10 out of the 57 urothelial carcinoma patients (17.5%) had node metastasis, and an additional 4 out of the 47 pN0 patients (4/47, 8.5%) had micrometastasis. The 2-year recurrence-free survival rates divided by pN stage were 82.4% for pN0, 66.7% for pNmicro+ and 12.5% for pN+ (three-sample log-rank test, P < 0.0001). Three out of the four patients with pNmicro+ were disease free at the last follow-up. CONCLUSIONS: We confirmed under extended lymph node dissection that a substantial proportion of the patients had node metastasis (pN+: n = 10 and pNmicro+: n = 4), and the pN stage influenced patient survival. Our observations of micrometastasis yielded additional evidence for the potential survival benefit of extended lymphadenectomy by eliminating microdisease.

[Risk factors for predicting severe leukopenia induced by docetaxel plus prednisolone in patients with Castration-Resistant Prostate cancer].

The purpose of this study was to extract the risk factors for GradeB3 leukopenia induced by docetaxel plus prednisolone (DP)therapy administered to patients with castration-resistant prostate cancer. Rates of 59% for GradeB3 leukopenia and 11% for FN were observed. On multivariate analysis, the pretreatment white blood cell count(OR=0.502, 95%CI: 0.292- 0.862, p=0.01)was significantly associated with severe leukopenia induced by DP therapy. In addition, on univariate analysis, the pretreatment platelet count, disease extent, and bilirubin level were significant factors. We consider it necessary to immediately treat patients with these risks with G-CSF.

Outcome of regional lymphadenectomy in accordance with primary tumor location on laparoscopic nephroureterectomy for urothelial carcinoma of the upper urinary tract: a prospective study.

PURPOSE: To determine the appropriate template of regional lymph node dissection (LND) at the time of laparoscopic nephroureterectomy (LNU) for patients with clinically node- negative urothelial carcinoma of the upper urinary tract. PATIENTS AND METHODS: This prospective study included 45 patients undergoing LND with LNU in accordance with our prospective rules regarding the area of LND. Perioperative, pathologic, and follow-up data were collected. Micrometastasis in lymph nodes (LNs) was later evaluated by immunohistochemistry (IHC). Recurrence-free survival (RFS) was calculated with the Kaplan-Meier method. RESULTS: The median number of LNs removed was 14 (range 1-33). One patient with pT3 disease had node metastasis based on routine pathologic examination, and IHC revealed micrometastases in two additional patients (pT2 in one and pT3 in one). Therefore, 15% (3/20) of patients with ≥pT2 disease had node disease. After surgery, six patients experienced minor complications (Grade 1 or 2), and Grade 5 gastrointestinal bleeding after aspiration pneumonia developed in one elderly male patient on the 45th postoperative day, which was not considered to be associated with LND. At the last follow-up, lung metastasis developed in four patients (pT1 in one, pT2 in one, and pT3 in two), and presacral lymph node metastasis developed in one patient with a lower ureteral tumor (pT2), which was not included in our prospective template for a lower ureteral tumor. LN recurrence within/ near the LND area was not observed in patients with pelvic/upper ureteral carcinoma. The 2-year nonurothelial RFS rate was 84%. CONCLUSIONS: We consider that the present template represents regional LNs for patients with clinically node-negative pelvic/upper ureteral carcinoma, while presacral LNs may be incorporated into the regional LND template for patients with clinically node-negative lower ureteral carcinoma.

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer.

OBJECTIVE: • To confirm the recurrence-preventing efficacy and safety of 18-month bacillus Calmette-Guérin (BCG) maintenance therapy for non-muscle-invasive bladder cancer. PATIENTS AND METHODS: • The enrolled patients had been diagnosed with recurrent or multiple non-muscle-invasive bladder cancer (stage Ta or T1) after complete transurethral resection of bladder tumours (TURBT). • The patients were randomized into three treatment groups: a maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks as induction therapy, followed by three once-weekly instillations at 3, 6, 12 and 18 months after initiation of the induction therapy), a non-maintenance group (BCG, 81 mg, intravesically instilled once weekly for 6 weeks) and an epirubicin group (epirubicin, 40 mg, intravesically instilled nine times). The primary endpoint was recurrence-free survival (RFS). RESULTS: • Efficacy analysis was performed for 115 of the full-analysis-set population of 116 eligible patients, including 41 maintenance group patients, 42 non-maintenance group patients and 32 epirubicin group patients. • At the 2-year median point of the overall actual follow-up period, the final cumulative RFS rates in the maintenance, non-maintenance and epirubicin groups were 84.6%, 65.4% and 27.7%, respectively. • The RFS following TURBT was significantly prolonged in the maintenance group compared with the non-maintenance group (generalized Wilcoxon test, P= 0.0190). CONCLUSION: • BCG maintenance therapy significantly prolonged the post-TURBT RFS compared with BCG induction therapy alone or epirubicin intravesical therapy.

Lymphoepithelioma-like carcinoma of the renal pelvis.

Lymphoepithelioma-like carcinoma (LELC), best known to occur in the nasopharynx, can arise in a variety of sites, such as the salivary gland, thymus, lung, stomach, skin and uroepithelium. Primary LELC of the uroepithelium is very rare and there is only limited information in the published reports. We managed a case of a 75-year-old woman who presented with nausea and gross painless hematuria. She was treated with laparoscopic nephroureterectomy and was diagnosed with a T1N1M0 LELC of the renal pelvis. Unlike nasopharyngeal lymphoepithelioma, immunohistochemical analysis of this urinary LELC was negative for the Epstein-Barr virus. Herein we report on one more case of primary LELC of the renal pelvis and review of the published reports, particularly those concerning Epstein-Barr virus expressions. Recognition of this tumor and complete resection are essential for saving patients.

Prevalence of renal cell carcinoma: a nation-wide survey in Japan, 2002.

OBJECTIVE: To investigate the incidence of renal cell carcinoma, classified by sex, age group and region in Japan, following a 5-year interval after a previous survey performed in 1997. METHODS: The survey was conducted between the beginning of January 2002 and the end of December 2002. A total of 1288 institutions in all 47 prefectures throughout Japan were requested to register cases. RESULTS: There were 7405 persons with renal cell carcinoma, consisting of 5063 males and 2342 females. Crude incidence rates were 8.2 and 3.6 per 100 000 population for men and women, respectively. Incidence rates in the Hokkaido region were highest followed by the Shikoku region. CONCLUSIONS: Despite incidence of renal cell carcinoma increasing to 7405 from the 6358 persons in 1997, statistical data reported by the Ministry of Health, Labor and Welfare indicate that rising age-adjusted death rate for this tumor reached a ceiling in the past decade. Early detection may have contributed to this current trend; however, further epidemiological research is required to fully elucidate this.

Surgical outcomes of partial nephrectomy for renal cell carcinoma: a joint study by the Japanese Society of Renal Cancer.

OBJECTIVE: A joint study was undertaken by the Japanese Society of Renal Cancer to investigate the present status of partial nephrectomy in Japan and to speculate about what may be the indications for partial nephrectomy in patients with renal cell carcinoma. METHODS: Data were tabulated for 469 patients from participating medical institutions and various clinical factors were investigated with regard to disease progression (local recurrence and distant metastasis). RESULTS: Disease progression was observed in 21 patients (4.5%). No significant relation to disease progression was observed for sex, laterality, tumor histology, grade and tumor size. Although patients with solitary tumors displayed excellent prognosis irrespective of tumor diameter, patients with multiple tumors displayed a high likelihood of disease progression. Patients older than 77 years old and patients with imperative indication were found to have a poorer prognosis. CONCLUSION: In patients with solitary tumors, partial nephrectomy can be actively performed, even if the patient displays elective indications and the tumor is >4 cm in diameter. In patients displaying multiple tumors with imperative indications, the decision whether to perform partial nephrectomy should be made by the patients and their physicians after considering the impact on curability and the quality of life.

Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy.

BACKGROUND AND AIMS: The aim of the present phase II study was to evaluate the efficacy of combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) in patients with recurrent urothelial cancer who had been treated with cisplatin-based chemotherapy. PATIENTS/METHODS: Eligible patients were those with histologically confirmed urothelial cancer who had progressed or relapsed after cisplatin-based chemotherapy. The PIN regimen consisted of paclitaxel 175 mg/m(2) on day 1; ifosfamide 4.5 g/m2 divided over days 1, 2, and 3; and nedaplatin 70 mg/m(2) on day 1; PIN was given every 28 days. RESULTS: Among the 32 patients enrolled in the study (median age, 66 years), complete and partial responses were obtained in 5 patients and 19 patients, respectively, with an overall response rate of 75% (95% confidence interval [CI], 59-91%). The median time to progression was 8 months (range, 0-50+ months) and the median survival was 22 months (range, 4-52+ months). The 1- and 2-year overall survival rates were 53.7 and 42.9%, respectively. All patients experienced Grade 3 or 4 neutropenia, while Grade 3 or 4 thrombocytopenia was seen in 8 patients; Grade 3 or 4 anemia was seen in 6 patients; Grade 3 neuropathy was observed in 1 patient, for whom the PIN therapy was discontinued. There were no treatment-related deaths. CONCLUSION: The PIN combination was highly active and tolerable in previously treated patients with urothelial cancer as a second-line treatment.

Differences in tumor core distribution between palpable and nonpalpable prostate tumors in patients diagnosed using extensive transperineal ultrasound-guided template prostate biopsy.

BACKGROUND: The authors performed extensive transperineal ultrasound-guided template prostate biopsies to investigate carcinoma core distribution. METHODS: Between August 2000 and May 2004, 371 men underwent template biopsies. Three hundred twelve patients had not undergone a previous biopsy (first group) and 59 had undergone previous transrectal sextant biopsies (repeat group). Of the 312 patients in the first group, 236 had normal digital rectal examination (DRE) findings (DRE- first group) and 76 patients had an abnormal DRE (DRE+ first group). A mean of 20.1 biopsy cores (range, 9-38 cores) was taken from the entire prostate. The region > 2.0 cm from the rectal face of the prostate was defined as the anterior region and the remaining area was defined as the posterior region. RESULTS: In the DRE- first group, the carcinoma core rate (number of tumor cores/number of biopsy cores) in the anterior region (7.2%) did not differ from that of the posterior region (7.3%) (P = 0.9635). However, in the DRE+ first group, the carcinoma core rate in the posterior region (22.0%) was found to be higher than in the anterior region (13.2%) (P < 0.0001). In the repeat group, the carcinoma core rate in the posterior region (3.1%) was significantly (P = 0.0008) lower than that exhibited in the anterior region (7.2%). CONCLUSIONS: The results of the current study suggest that nonpalpable prostate carcinoma is distributed equally within the entire prostate, although palpable carcinoma is distributed mainly in the posterior region and many of the tumor foci in the anterior region may be missed by a transrectal sextant biopsy. The examination of radical prostatectomy specimens is required to prove these results.