Kaku, Haruki

We evaluated the efficiency and toxicity of estramustine phosphate (ECT), ifosfamide (IFM) and cisplatin (CDDP) combination chemotherapy in twenty-one patients with hormone-refractory prostate cancer (HRPC), for which there is currently no effective treatment. Patients received a daily dose of 560 mg ECT in combination with 1.2 g/m2 IFM on days 1 to 5 and 70 mg/m2 CDDP on day 1. This combination therapy was given every 3 to 4 weeks. An objective response of more than 50% reduction in prostate-specific antigen was observed in 9 of 18 patients (50%), and a more than 50% reduction in bi-dimensionally measurable soft-tissue lesions was observed in 2 of 7 patients (29%). The median duration of response among the cases showing partial response was 40 weeks, while the median duration of response of overall partial-response plus stable cases was 30 weeks. The median survival duration of all cases was 47 weeks. Toxicity was modest and acceptable. In conclusion, the ECT, IFM and CDDP combination chemotherapy regimen is a viable treatment option for HRPC. However, in comparison with our previous chemotherapy regimen of IFM and CDDP, no additional long-lasting effects resulting from the inclusion of ECT could be affirmed.

We have recently shown that a new therapeutic modality using the REIC/Dkk-3 gene (Ad-REIC) is effective against various human cancers, including those of prostate, testis and breast origins. The aim of the present study was to examine the sensitivity of bladder cancers to Ad-REIC and to clarify the molecular mechanisms that determine sensitivity/resistance. We found that 2 human bladder cancer cell lines, T24 and J82, are resistant to Ad-REIC. In T24 and J82 cells, the ER stress response and activation of JNK were observed in a manner similar to that in the sensitive PC3 cells. Translocation of Bax to mitochondria occurred in PC3 cells but not in T24 and J82 cells. Bcl-2 was remarkably overexpressed in T24 and J82 compared with the expression levels in sensitive cell lines. Treatment of T24 and J82 cells with a Bcl-2 inhibitor sensitized the cells to Ad-REIC-induced apoptosis. The results indicate that some human bladder cancers are resistant to apoptosis induced by overexpression of REIC/Dkk-3, which is at least in part due to up-regulation of Bcl-2. These results provide a basis for possible use of Bcl-2 as a marker of sensitive cancers and to try to sensitize resistant cancers to Ad-REIC by down-regulation of Bcl-2.

This study was undertaken to reveal the trends of prostate cancer and the outcome of treatment modalities for each disease stage in patients in a single institute over a 10-year period. From January 1994 through December 2003, 420 consecutive patients with previously untreated and histologically confirmed prostate cancer were analyzed for annual distributions of disease stages and treatment modalities and for long-term clinical progression-free survival, prostate cancer-specific survival, and prostate-specific antigen (PSA) failure-free survival rates for each stage and treatment modality. Annual trends showed that the number of patients, especially those with clinically localized cancer, increased dramatically. The 5-year disease-specific survival rates for patients with clinically localized disease were 100 percent for all treatment modalities, including hormonal therapy alone. Patients with PSA levels less than 10 ng/ml showed an 81 percent 5-year PSA failure-free survival rate with radical prostatectomy. Stage C patients treated by surgery or radiation-based therapy with concomitant hormonal therapy obtained 93 percent and 100 percent cause-specific survival rates, respectively, and those treated by hormonal therapy alone showed a 79 percent rate. The number of patients with localized prostate cancer was increasing in this decade. While long-term hormonal therapy alone was highly efficient in controlling localized prostate cancer, radical therapies in conjunction with neo-adjuvant hormonal therapy produced better survival rates in cases of locally advanced disease.

The aim of this study was to reveal the clinical features of anterior urethral recurrence in patients with superficial bladder cancer, and to determine the appropriate treatment. Three hundred and three patients with superficial bladder cancer, who were newly diagnosed and initially treated conservatively in our hospital between 1965 and 1990, were followed for at least 5 years and their clinical outcomes were analyzed. Clinical factors, including anterior urethral recurrence, were evaluated statistically regarding tumor progression. Eight patients (2.6%) had anterior urethral recurrence following superficial bladder cancer. Twenty-four patients (7.9%) had tumor progression and 149 (49.2%) had tumor recurrence. In a multivariate analysis using a logistic model, anterior urethral recurrence was the most important factor, followed by histological grade. Four of 5 patients who were treated for anterior urethral recurrent tumors by transurethral resection showed progression and died of the cancer within one year. Two of the remaining three patients who underwent radical cysto-urethrectomy at the time of anterior urethral recurrence survived. Anterior urethral recurrence following superficial bladder cancer is a predictor for rapid subsequent malignant progression. Once there is anterior urethral recurrence, radical intensive therapy, including radical cysto-urethrectomy, should be carried out immediately.

We evaluated the need for transurethral biopsy at first follow-up after intravesical bacillus Calmette-Guerin (BCG) therapy for superficial bladder cancer. The records of 84 patients with superficial bladder cancer who received a 6- or 8-week course of BCG were reviewed. Pathological results before BCG, cystoscopic findings, urinary cytology, and biopsy results for evaluation of BCG therapy were reviewed. All 19 patients with positive urinary cytology had evidence of positive bladder biopsy results. Fifty-three of 54 patients (98.1%) with no visible recurrent tumor and negative urinary cytology demonstrated negative pathological results on bladder biopsy. When not found in conjunction with positive urinary cytology, erythematous mucosa on cystoscopy was not an indicator of tumor recurrence or residual cancer. In conclusion, routine transurethral biopsy of the bladder for evaluating the response to BCG intravesical therapy is not necessary in patients who have no visible tumor on cystoscopy and negative urinary cytology./