Age at diagnosis on prostate cancer survival undergoing androgen deprivation therapy as primary treatment in daily practice: results from Japanese observational cohort.

OBJECTIVES: Primary androgen deprivation therapy (PADT) had been used extensively in Japan than in the USA and European countries regardless of the disease risk or patient's age. To illustrate the consequence of PADT from daily clinical practice, we evaluated the relationship among age, disease risk, and survival of patients with prostate cancer treated by PADT in largest Asian cohort. PATIENTS AND METHODS: The 19,246 men subjected to PADT enrolled in the Japan Study Group of Prostate Cancer were enrolled for the present analysis. Patients were divided into four groups based on age at diagnosis: age <66, 66-70, 71-75, and >75. Risk was stratified according to the Japan Cancer of the Prostate Risk Assessment (J-CAPRA). Multivariate competing risks regression analysis was performed for OS and PFS. RESULTS: There was downward stage migration over age. Among men aged >75 years, 34.1 % had nodal or distant metastatic disease. In contrast, 56.0 % of patients aged <66 years presented with advanced disease. The modality of hormonal therapy varied with age across risk groups; the younger age group showed a higher proportion of maximal androgen blockade, while the proportion of monotherapy use was higher in older men. The likelihood of low-risk disease by J-CAPRA classification increased significantly with increasing age (p < 0.0001 by Pearson's chi-square test). The same as OS, the PFS rate increased with age until after the age of 75. Men aged 71-75 had better survival rates even after adjustments for treatment modality alone, or for treatment modality plus disease risk. CONCLUSIONS: Age cohorts do affect orientation toward favorable disease course after PADT with men aged 71-75 being benefiting more from PADT than other age groups.

Efficacy of flutamide-combined androgen blockade therapy in advanced prostate cancer patients: a phase III randomized, comparative trial.

The efficacy of combined androgen blockade therapy consisting of flutamide, a nonsteroidal antiandrogen, plus an LH-RH agonist (F-CAB) was investigated in Japanese patients with untreated advanced prostate cancer (clinical stage D). The primary endpoint was overall survival (OS), while the secondary endpoints were disease-specific survival (DSS), progression- free survival (PFS), reduction of prostate specific antigen (PSA), anti-tumor effects, quality of life (QOL), and adverse drug reactions (ADRs). As of the median observation period of 1,293.5 days, the F-CAB significantly prolonged DSS and PFS relative to LH-RH monotherapy (log rank test: p=0.0343 and 0.0017, respectively). The results of this study indicate the potential of F-CAB as a useful treatment for untreated advanced prostate cancer. Although additional study is considered necessary to determine the daily dosage of flutamide, the anti-tumor effects obtained from this study indicated that 375 mg/day is appropriate as a daily dosage, and 250 mg/day can also be considered when concern exists regarding the occurrence of complications or the development of ADRs, including liver function disorders. [Funded by Nippon Kayaku Co., Ltd., Japic CTI-050101].

Evaluation of primary androgen deprivation therapy in prostate cancer patients using the J-CAPRA risk score.

PURPOSE: To determine the influence of maximal androgen blockade (MAB) and non-MAB hormonal therapy with an luteinizing hormone releasing hormone (LHRH) analog on overall survival of prostate cancer patients in the Japan Study Group of Prostate Cancer (J-CaP) registry according to risk, as assessed using the novel J-CAPRA risk instrument. To undertake a multivariate analysis combining J-CAPRA risk score, type of hormonal therapy and comorbidities, in order to assess their impact on overall survival. METHODS: The J-CaP database includes men in Japan diagnosed with any stage of prostate cancer between 2001 and 2003 and treated with primary androgen deprivation therapy (PADT), as monotherapy or in combination. A total of 26,272 men were enrolled and of these 19,265 were treated with PADT. This analysis was undertaken using the latest data set (30 April, 2010) including a total of 15,727 patients who received PADT and had follow-up data for periods ranging from 0 to 9.2 years. RESULTS: MAB for prostate cancer patients with intermediate- or high-risk disease has a significant benefit in terms of overall survival compared with LHRH analog monotherapy or surgical castration alone. Better results may be achieved in older (≥75 years) patients. Patient comorbidities are an important factor in determining overall survival, notably in older patients, and should be considered when selecting therapy. CONCLUSIONS: Based on large-scale registry data, this report is the first to analyze the outcomes of MAB therapy in patients with prostate cancer at a wide range of disease stages. MAB therapy may provide significant survival benefits in intermediate- and high-risk patients.

Single- and multiple-dose pharmacokinetics, safety and tolerability of zibotentan (ZD4054) in Chinese men with advanced solid tumors.

PURPOSE: The endothelin axis and the endothelin A (ET(A)) receptor have been implicated in tumor development and bone metastasis. This study aimed to investigate the pharmacokinetic (PK) and safety profiles of the specific ET(A) receptor antagonist, zibotentan, in elderly, male Chinese patients with advanced solid tumors. The PK data generated in these Chinese patients were further compared with those previously reported in Japanese and Caucasian patient populations. METHODS: In this Phase I, open-label study, patients received a single dose of zibotentan 10 mg on Day 1, followed by a 72-h washout period and 12 consecutive days of once-daily zibotentan 10 mg. RESULTS: Fifteen patients received at least one dose of zibotentan 10 mg. Exposure was demonstrated in all patients and the PK profiles following single dosing and multiple dosing showed relatively rapid absorption, decline in a monophasic manner, a modest amount of accumulation, and relatively low apparent clearance and volume of distribution. Zibotentan was well tolerated with no new safety concerns. Adverse events reported in >1 patient were pyrexia (n = 4), constipation (n = 3), headache (n = 3) and peripheral edema (n = 2). Comparative analysis found no evidence of significant differences in zibotentan exposure between the Chinese patients in our study, and the previous Japanese and Caucasian studies. CONCLUSIONS: The PK and safety profiles of zibotentan determined in this Chinese patient population are similar to those previously reported. Our findings suggest no clinically relevant inter-ethnic differences in zibotentan disposition between the patient populations analyzed.

Phase III trial of everolimus in metastatic renal cell carcinoma: subgroup analysis of Japanese patients from RECORD-1.

OBJECTIVE: To assess the efficacy and safety of everolimus in Japanese patients with metastatic renal cell carcinoma. METHODS: A subgroup analysis of the pivotal Phase III, randomized, double-blind, placebo-controlled trial of everolimus 10 mg/day in patients with disease progression after treatment with sorafenib, sunitinib or both assessed outcomes in Japanese participants. Results were compared with those for the overall study population. RESULTS: The final trial analysis included 24 Japanese patients (everolimus, n= 15; placebo, n = 9). Median progression-free survival in the Japanese subpopulation was 5.75 months (95% confidence interval, 4.90 months to not reached) with everolimus and 3.61 months (95% confidence interval, 1.91-9.03 months) with placebo (hazard ratio, 0.19; 95% confidence interval, 0.05-0.83). Median overall survival was not reached with everolimus and was 14.9 months (95% confidence interval, 11.0-16.8 months) with placebo (hazard ratio, 0.30; 95% confidence interval, 0.07-1.27). Overall, efficacy and safety were similar when comparing the Japanese and overall populations. In the Japanese subpopulation, the most common adverse events with everolimus were stomatitis, infections and rash. Four Japanese subjects (27%) developed Grade 1 (n = 2) or 2 (n = 2) pneumonitis (all reversible and allowing for continuation of therapy, after interruption, steroids and dose reduction for both Grade 2 cases), with a lower pneumonitis incidence of 14% in the overall population (albeit associated with a Grade 3 incidence of 4%). CONCLUSIONS: These findings suggest that the demonstrated benefits of everolimus in the overall trial population are similar in Japanese patients with metastatic renal cell carcinoma.

Multicenter phase II trial of S-1 in patients with cytokine-refractory metastatic renal cell carcinoma.

PURPOSE: This phase II multicenter trial was conducted to evaluate the activity and safety of S-1 in Japanese patients with metastatic renal cell carcinoma (mRCC). We also examined the relation between response and mRNA expression levels of enzymes involved in the metabolism of fluorouracil (FU). METHODS: Patients with mRCC who had received nephrectomy in whom cytokine-based immunotherapy was ineffective or contraindicated were studied. S-1 was administered orally at 80-, 100-, or 120-mg daily, assigned according to body surface area, on days 1 to 28 of a 42-day cycle. The primary end point was the objective response rate. The mRNA expression levels of FU-related enzymes were measured by reverse-transcriptase polymerase chain reaction in formalin-fixed, paraffin-embedded specimens of tumors obtained at nephrectomy. RESULTS: A total of 45 eligible patients were enrolled. Eleven (24.4%) of 45 patients had partial responses to S-1, and 28 (62.2%) had stable disease. Median progression-free survival was 9.2 months. The severity of most adverse events was mild to moderate. The most common grade 3/4 drug-related adverse events were neutropenia (8.9%) and anorexia (8.9%). The expression level of thymidylate synthase (TS) mRNA was significantly lower in patients who responded to treatment (t-test, P = .048), and progression-free survival was significantly longer in patients whose TS mRNA expression levels were below the median value, as compared with those with higher levels (log-rank test, P = .006). CONCLUSION: S-1 is active against cytokine-refractory mRCC. Quantification of TS mRNA levels in tumors before treatment may facilitate prediction of the response of mRCC to S-1.

Efficacy of S-1 in patients with castration-resistant prostate cancer: a phase II study.

OBJECTIVES: This study was conducted to evaluate the efficacy and safety of S-1, an oral fluoropyrimidine derivative, in Japanese patients with castration-resistant prostate cancer (CRPC). The primary endpoint was prostate-specific antigen (PSA) response. METHODS: In this open-label phase II study, S-1 was started at a dose of 80, 100 or 120 mg daily based on body surface area (BSA) for 28 days, followed by 14 days of rest. Patients with histological proof of prostate cancer refractory to hormonal therapies were eligible. Patients who received prior chemotherapy were excluded. All patients provided written informed consent. To observe 20% confirmed PSA response, 33 assessable patients were needed. Treatment was continued until disease progression or the development of intolerable toxicity. RESULTS: A total of 35 eligible patients were enrolled. The median number of treatment cycles was 3. PSA response was observed in 8 patients (22.9%, 90% CI 11.9-37.5), including 3 in which (8.6%) the PSA level normalized. The median overall survival was 25.4 months. The most common treatment-related grade 3 toxicity was anorexia (14.3%). There was no death during the study. CONCLUSION: S-1 monotherapy is active against castration-resistant prostate cancer and has acceptable toxicity.

Maintenance intravesical bacillus Calmette-Guérin instillation for Ta, T1 cancer and carcinoma in situ of the bladder: randomized controlled trial by the BCG Tokyo Strain Study Group.

OBJECTIVES: We carried out a prospective, randomized, controlled trial to investigate the efficacy and safety of both induction and maintenance therapy with intravesical instillation of bacillus Calmette-Guérin (BCG) for high-risk non-muscle invasive bladder cancer (NMIBC). METHODS: Intravesical instillation of 80 mg Tokyo strain was given to patients with high-risk NMIBC, including carcinoma in situ (CIS), once weekly for eight consecutive weeks as induction therapy. Patients who achieved complete response (CR) were randomly assigned to either the maintenance group or the observation group. RESULTS: A total of 90 patients were enrolled. After induction therapy, 75% of the patients achieved CR and 53 of them were enrolled in the randomized comparative phase. A total of four maintenance instillations were given. Median follow-up was 26.5 and 28.7 months after randomization in the maintenance and the observation group, respectively. Although it was not statistically significant, the 2-year recurrence-free survival rate in the maintenance group (95.8%) was higher than that in the observation group (74.1%, P = 0.078). Univariate analysis identified maintenance therapy as a significant factor influencing recurrence. During induction therapy, 82.2% of patients experienced urination-related adverse drug reactions, but most events were not serious. There were fewer adverse drug reactions with maintenance therapy than with induction therapy. Neither induction therapy nor maintenance therapy reduced patients' quality of life (QOL). CONCLUSIONS: These findings show high levels of efficacy and safety of BCG induction treatment for high-risk NMIBC, and suggest that the number of maintenance instillations could probably be reduced without reducing treatment efficacy or influencing QOL.

An early phase II trial of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma.

PURPOSE: S-1, an oral anticancer agent, contains tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) at a molar ratio of FT:CDHP:Oxo = 1:0.4:1. The aim of this trial was to investigate the efficacy and safety of S-1 in Japanese patients with cytokine-refractory metastatic renal cell carcinoma (RCC). METHODS: We conducted a non-randomized, open-label trial in Japanese patients with metastatic RCC who had received nephrectomy and had failed cytokine-based immunotherapy. The primary endpoint was response rate. S-1 40-60 mg based on the body surface area was administered twice daily (80-120 mg/day) for 4 consecutive weeks, followed by a 2-week rest period; cycles were repeated every 6 weeks. Patients continued treatment until disease progression, unacceptable toxicity, or withdrawal of consent. RESULTS: A total of 20 eligible patients were enrolled. Among these, 3 patients had partial response, yielding objective response rate of 15%; 13 patients had no change; 4 patients had progressive disease. The median time-to-progression and median overall survival were 12.0 and 25.7 months, respectively. The initial adverse event was generally mild to moderate in severity. The most common grade 3/4 drug-related hematological and non-hematological adverse events were neutropenia (20.0%) and anorexia (20.0%), respectively. CONCLUSIONS: S-1 is active and well tolerated for the treatment of cytokine-refractory metastatic RCC.

Discrepancy between local and central pathological review of radical prostatectomy specimens.

PURPOSE: Pathological assessment of radical prostatectomy specimens has not been uniform among pathologists. We investigated interobserver variability of radical prostatectomy specimen reviews between local and central pathologists. MATERIALS AND METHODS: We collated data from 50 institutions on 2,015 patients with cT1c-3 prostate cancer who underwent radical prostatectomy between 1997 and 2005. All radical prostatectomy specimens were retrospectively reevaluated by a central uropathologist. Gleason score, extracapsular extension, seminal vesicle invasion, lymph node involvement, positive surgical margin, year of diagnosis and pathology volume were recorded. RESULTS: The exact concordance rate of Gleason score between local and central review was 54.8%, and under grading and over grading rates at local review were 25.9% and 19.2%, respectively. Spearman's rank correlation coefficient was 0.61 for local and central radical prostatectomy Gleason score. The exact concordance rate of Gleason score 8-10 at local review was significantly lower than that of Gleason score 5-6, 3 + 4 and 4 + 3 at local review (p = 0.011, <0.001 and 0.006). Exact concordance rates between local and central review for extracapsular extension, seminal vesicle invasion, lymph node involvement and positive surgical margin were 82.5%, 97.6%, 99.6% and 87.5%, respectively. High volume institutions and recently diagnosed cohorts showed significantly higher exact concordance rates between local and central review for radical prostatectomy Gleason score and other pathological features (all p <0.001). CONCLUSIONS: High volume institutions and recent series show higher concordance between local and central review of radical prostatectomy pathology. However, concordance for high grade Gleason score, extracapsular extension and surgical margin status remains poor. Radical prostatectomy specimens should be reevaluated in a multi-institutional study for more accurate pathological data.

[Malignant paraganglioma responsive to CVD therapy and radiation therapy : a case report].

The patient, a 55-year-old man, had undergone surgery for retroperitoneal paraganglioma at the age of 45. In February 2006, he visited our hospital with the chief complaint of metastatic tumors detected by a thorough checkup. Computed tomographic (CT) scan revealed a large tumor in the right kidney hilar region and a left supraclavicular lymphadenopathy. Histopathological and immunohistochemical findings of the biopsy specimen taken from the left supraclavicular lymph node led to the diagnosis of recurrent malignant paraganglioma. 123I-MIBG scintigram showed no radioisotope accumulation consistent with the tumor. From April 2006 to September 2006, he received 8 cycles of CVD therapy (cyclophosphamide, vincristine, and dacarbazine). The tumor temporarily responded and was reduced to one-third in size, but soon it became resistant to CVD therapy. In March 2007, because the tumor had begun to grow, he received the 9th course of CVD therapy, but the tumor response was PD. Subsequently, palliative radiation therapy of 50 Gy in 25 fractions was administered and was temporarily effective. The CVD therapy and radiation therapy were considered to be effective for this case. In May 2008, he died 25 months after the start of CVD therapy.

Brain metastases from testicular germ cell tumors: a retrospective analysis.

OBJECTIVES: To review our series of testicular germ cell tumors with brain metastases and to establish an optimal treatment strategy for them. METHODS: Twenty-seven cases of testicular germ cell tumors from three institutions were retrospectively reviewed. RESULTS: Twenty-six were non-seminomatous tumors and only one was a seminoma. Based on the International Germ Cell Consensus Classification, two cases were classified as good prognosis, seven as intermediate prognosis and 18 as poor prognosis. Chemotherapy was carried out in all patients. Additionally, whole-brain radiotherapy was performed in 10 cases, stereotactic radiosurgery in six, whole-brain radiotherapy combined with stereotactic radiosurgery in three and complete surgical resection in five. Three patients received chemotherapy only. Cancer-specific 5- and 10-year survival rates were both 35.9%. The prognosis of those with brain metastases at the time of diagnosis tended to be better than those developing brain metastases during treatment. Those with a single brain metastasis showed significantly better survival than those with multiple brain metastases. No other significant prognostic factor was found at multivariate analysis. CONCLUSION: Testicular germ cell tumors with brain metastases can be managed with the combination of whole-brain radiotherapy, stereotactic radiotherapy, and/or surgical resection in combination with chemotherapy.

Surveillance following orchiectomy for stage I testicular seminoma: long-term outcome.

OBJECTIVES: To report the long-term outcome of surveillance for stage I seminoma at a single institution in Japan. METHODS: A retrospective review of medical records of 64 patients who underwent orchiectomy between January 1982 and December 2005 was carried out. All of them were managed by surveillance for stage I seminoma. RESULTS: Median follow-up time was 123.8 months. Of the 64 patients, seven developed relapse. Four relapses occurred within the first year after orchiectomy, but three occurred over 4 years after orchiectomy. The actuarial relapse-free rates at 5, 10, and 15 years were 92.1%, 90.0%, and 86.0%, respectively. All patients received salvage chemotherapy at relapse. Four of these seven patients were alive without evidence of disease. One patient died of seminoma and one was alive with this disease. The remaining one patient died of leukemia without secondary relapse of seminoma. T classification was a statistically significant (P = 0.028) risk factor for relapse on univariate analysis. In T1 patients, relapse-free rates at 5, 10, and 15 years were all 97.1%, whereas in T2/T3 patients the corresponding relapse-free rates were 86.4%, 82.1%, and 71.8%, respectively. CONCLUSIONS: The relapse-free rate in the present study was similar to previous reports. Late relapse should be considered during surveillance.

Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival.

BACKGROUND: A previously reported, double-blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone-releasing hormone agonist (LHRH-A) plus bicalutamide 80 mg versus LHRH-A plus bicalutamide-matching placebo (LHRH-A monotherapy). The analysis at a median follow-up of 2.4 years indicated that CAB significantly (P<.001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long-term follow-up (median, 5.2 years) were analyzed. METHODS: All deaths irrespective of cause and all prostate cancer-specific deaths were recorded. The data were analyzed using Cox regression analysis and the log-rank test. RESULTS: At a median follow-up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH-A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95% confidence interval, 0.60-0.99; P=.0498; log-rank test: P=.0425). The difference in cause-specific survival between the 2 groups was not significant. The achievement of a prostate-specific antigen (PSA) nadir concentration

[Rectourethral fistula after radical retropubic prostatectomy: a case report].

The patient, a 56-year-old man, had surgery for anal fistula at the age of 28. In August 2007, he underwent a radical retropubic prostatectomy (RRP) for prostate cancer. Rectal injury was not recognized during the operation. However, on the 8th postoperative day, fecaluria appeared, and rectourethral fistula was diagnosed. We attempted conservative therapy including diverting colostomy and continued drainage using a urethral catheter. Subsequently, the fistula closed spontaneously 3 months after RRP. Eight months after RRP, we performed a transanal repair of rectal mucosa based on the rectal wall advancement flap procedure. The postoperative course was uneventful, and the colostomy was closed in July 2008. By April 2009, he had normal voiding and full anal continence without fistula recurrence.

Evaluation of quality of life in patients with previously untreated advanced prostate cancer receiving maximum androgen blockade therapy or LHRHa monotherapy: a multicenter, randomized, double-blind, comparative study.

PURPOSE: To assess quality of life (QOL) data from a double-blind Phase III study evaluating bicalutamide (Casodex) 80 mg as part of maximum androgen blockade (MAB) in patients with previously untreated advanced prostate cancer. METHODS: Patients with untreated stage C/D prostate cancer were randomized to MAB with bicalutamide plus a luteinizing hormone-releasing hormone agonist (LHRHa) or LHRHa monotherapy. QOL was evaluated at baseline and at weeks 1, 5, and 24 using the Japanese version of the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. RESULTS: A total of 203 patients were assessed for QOL. The MAB group had more rapid and greater improvements in "emotional well-being" and "prostate cancer-specific issues" domain scores than the monotherapy group. Further analysis of "prostate cancer-specific issues" revealed that, compared with monotherapy, MAB provided a greater improvement in "micturition disorder"-related QOL. Complete improvement rates for items related to "pain and micturition disorder" were also higher with MAB. Item scores of "pain and micturition disorder" did not correlate strongly with prostate-specific antigen levels or tumor size. Fewer patients who had deterioration in their "pain and micturition disorder" item scores at week 1 in the MAB group than the monotherapy group. CONCLUSIONS: Maximum androgen blockade with bicalutamide plus LHRHa did not reduce the overall QOL of patients with previously untreated advanced prostate cancer. MAB was superior to monotherapy in achieving early improvement of QOL related to micturition disorder and pain.

Reduction of irradiation volume and toxicities with 3-D radiotherapy planning over conventional radiotherapy for prostate cancer treated with long-term hormonal therapy.

BACKGROUND: As hormonal therapy has an influence not only on outcome but also on toxicities, we compare the efficacy of three-dimensional radiotherapy planning (3D-RTP) and of conventional radiotherapy (Conv-RT) in association with long-term hormonal therapy in reducing toxicity of treatment. PATIENTS AND METHODS: A retrospective case-control study was performed comparing the frequency of radiation toxicity between 63 Conv-RT and 52 3D-RTP patients with locally advanced prostate cancer (intermediate to high risk) treated with combined hormonal therapy. The average duration of neoadjuvant treatment was 7 months (1-38 months) and that of adjuvant treatment was 38 months (4-94 months). Patients were treated with 70 Gy of box field radiotherapy for the same clinical target volume (60 Gy prostate + seminal vesicle and 10 Gy boost to prostate). RESULTS: Treatment volumes (= X(RL) x Y(SI) x X(AP), where X(RL) = right left length of anterior-posterior portals, X(AP) = anterior posterior length of lateral portals and Y(SI) = superior inferior length of anterior-posterior portals) were significantly smaller in the 3D-RTP group (630 +/- 130 cm3) than in the Conv-RT group (1036 +/- 223 cm3) (p < 0.0001). Acute side-effects in urological tracts (GU) were associated with XRL (p = 0.02), Y(SI) (p = 0.008) and treatment technique (Conv-RT vs. 3D-RTP: p = 0.01). The frequency of acute gastrointestinal tract (GI) toxicity was associated with X(RL) (p = 0.02), X(AP) (p = 0.03). Late GU toxicities were associated with YAP (p = 0.02) and X(RL) (p = 0.03). Treatment technique was the determinant of late GI toxicities (p = 0.03). Frequency of late GI toxicities of G2 or more was reduced from 35% in the Conv-RT group to 15% in the 3D-RTP group (p = 0.03, odds ratio = 0.43). Patients with late GI toxicity received longer periods (39 +/- 19 months) of adjuvant hormonal therapy than the patients without (31 +/- 18 months, p = 0.04). Prostate-specific antigen (PSA) failure-free survival rates at 3 years were 92% for the 3D-RTP group and 90% for the Conv-RT group (73% at 5 years, 67% at 10 years). Overall survival rates were 97% (3-year), 91% (5-year), and 91% (10-year) in the Conv-RT group, compared to 100% at 3 years in the 3D-RTP group. CONCLUSION: Long-term hormonal therapy has the potential to improve outcome but induce late GI toxicity. 3D-RTP simultaneously reduced treatment volume and frequency of acute urinary and late GI toxicities even with long-term hormonal therapy.

Current status of endocrine therapy for prostate cancer in Japan analysis of primary androgen deprivation therapy on the basis of data collected by J-CaP.

BACKGROUND: Based on the data of current status of endocrine therapy for prostate cancer registered in the Japan Study Group of Prostate Cancer (J-CaP), we conducted an analysis of primary androgen deprivation therapy (PADT) and an interim analysis of the prognosis. METHODS: Of the 26 272 cases registered in the server of J-CaP, the 19 409 cases initially receiving PADT were included in this study. The initial therapy was divided into eight categories according to its features. RESULTS: Of the 19 409 patients, 1513 (7.8%) were given anti-androgen monotherapy, 955 patients (4.9%) surgical castration only, 1001 patients (5.2%) surgical castration + anti-androgen, 3015 patients (15.5%) LHRH monotherapy, 1658 patients (8.5%) LH-RH + short-term anti-androgen, 10 434 patients (53.8%) LH-RH + anti-androgen, 37 patients (0.2%) watchful waiting and 796 patients (4.1%) other therapy. In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage. CONCLUSIONS: The pattern of PADT is more typical in Japan compared with that in the United States. Patients who received MAB accounted for 59.0% of all the patients. MAB tends to be more often selected for patients who are rated as being at high risk on the basis of high Gleason score or PSA level upon diagnosis in each clinical stage of the disease. Investigations of the outcome are on-going and they will make clear the significance of this trend in Japan.

The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but dwindling difference in incidence rates of prostate cancer in various regions of Asia should be studied while the opportunity lasts. Session 2 was devoted to 6 presentations on detection rates by biopsy in each country. Although biopsy is the gold standard for detecting prostate cancer in most areas, indications for conducting biopsy are different in each country. For example, in Indonesia doctors may use PSAD 0.15 as the cutoff level. TRUS-guided biopsy is most widely used in Asian countries. Traditional sextant biopsy is often performed, although multiple-core biopsy is commonly available and associated with better detection rates, especially in men with large prostate volume. Positive DRE, high PSA, and older age were identified as factors associated with high biopsy detection rate, although elevated PSA has limited specificity. First biopsy in men with elevated PSA had a positive detection rate of approximately 30% in all countries. Community-based screening in some countries has an overall detection rate of approximately 1%. The favorable treatment modality for HRPC was the subject of the final session. First priority for doctors in all 6 countries is to maintain serum testosterone at castration level. Many therapeutic options are available, from cytotoxic drugs to traditional herbal medicines Chemotherapeutic agents such as estramustine, docetaxel, cyclophosphamide, and mitoxantrone are often given to patients with HRPC although not all are available in every country. Prednisone and dexamethasone are used for secondary hormonal therapy. External beam radiotherapy, radioisotopic drugs such as strontium 89, and bisphosphonates are common choices to control bone pain.

[Cost-effectiveness analysis of maximum androgen blockade for Japanese men with advanced prostate cancer].

Like other countries, Japan is facing the problem of rising medical costs associated with aging of the population, and therefore the cost-effectiveness of medicines has become increasingly important. Maximum androgen blockade (MAB) therapy, which is being widely used for advanced prostate cancer, has proved useful in clinical studies but it requires the additional use of an anti-androgen in contrast with luteinizing hormone releasing hormone agonist (LHRHa) monotherapy, raising a concern about the increase medical costs. Thus, based on the results of a Japanese Phase III study of bicalutamide we performed a cost-effectiveness analysis. We constructed a Markov model to express the changes in prognosis following MAB therapy and LHRHa monotherapy for advanced prostate cancer and the cost and effectiveness (survival) were simulated. As a result, the expected costs of MAB therapy and LHRHa monotherapy were 5,240,000 yen and 3,660,000 yen, respectively, with expected survival durations of 7.45 and 6.44 years. The incremental cost-effectiveness ratio for MAB therapy was 1,560,000 yen/life-year saved, lower than the established threshold (6,000,000 yen/life-year saved), and a sensitivity analysis confirmed the robustness of this result. Therefore, the incremental cost of bicalutamide was considered worth it in view of the therapeutic effect, suggesting that MAB therapy is a highly cost-effective therapy.