Efficacy of short-term androgen deprivation with high-intensity focused ultrasound in the treatment of prostate cancer in Japan.

OBJECTIVES: To determine whether combining short-term neoadjuvant androgen deprivation therapy (NADT) with high-intensity focused ultrasound (HIFU) had a significant benefit in a large population of men with nonmetastatic prostate cancer (CaP). METHODS: We evaluated the records of 530 patients whose prostate-specific antigen (PSA) level at diagnosis was 30 ng/mL or less and whose follow-up period was not less than 12 months, at seven investigational sites. Two hundred seventy patients had received NADT (within 6 months), and 260 had not. The primary outcome measure was disease-free survival according to the combined criteria satisfying the Phoenix definition (less than nadir + 2), negative prostate biopsy, and no findings of distant metastasis after the last HIFU treatment. The significance of the differences of values or the distributions of each parameter between two groups was evaluated with a Mann-Whitney U test, unpaired t test, or chi-square test, and a multivariate Cox proportional hazards model was used to evaluate the prognostic relevance of preoperative parameters. RESULTS: Statistical analyses showed that the NADT group had worse disease (higher PSA and risk group) than the HIFU-only group. Variables shown by multivariate analyses to be significant prognostic parameters were pretreatment PSA level, clinical stage, and no use of NADT. Short-term NADT significantly improved the 3-year disease-free survival rate of patients with intermediate-risk and high-risk CaP. During follow-up the frequencies of complications did not differ significantly with or without NADT. CONCLUSIONS: Our retrospective study suggests that combining short-term NADT with HIFU treatment is of significant clinical benefit to intermediate-risk and high-risk CaP patients without increasing the likelihood of complications.

Low pre-radiotherapy prostate-specific antigen level is a significant predictor of treatment success for postoperative radiotherapy in patients with prostate cancer.

BACKGROUND: The optimal role of postoperative radiotherapy for patients with prostate cancer remains undefined. MATERIALS AND METHODS: The medical records of 70 patients (median age: 66 years), who had received radical radiotherapy (RT) between the years 1996 and 2004 after radical prostatectomy (RP), were analyzed. Fifteen patients had received immediate adjuvant RT, while the other 55 patients had received salvage therapy. Hormonal therapy had been performed in 28 patients before RT and continued in two of them concurrently with RT. A median dose of 60 Gy was delivered to the prostate bed. Pelvic node irradiation was performed in all patients. RESULTS: After a median follow-up period of 23 months, 21 patients had experienced biochemical failure. Actuarial 3- and 5-year biochemical relapse-free survival estimates were 67.4%. No patient had local failure, although distant metastases with biochemical failure were found in five patients. On univariate analysis, the following were significant for biochemical failures: seminar vesicle involvement, serum PSA level >1 ng/ml before RT, pathological pelvic node involvement, RT indication (adjuvant vs. salvage) and Gleason score. However, only the serum PSA level before RT was significant on multivariate analysis. CONCLUSION: Postoperative RT with a pre-RT PSA level <0.1 ng/ml seemed to be effective in patients with prostate cancer.

Importance of urinary interleukin-18 in intravesical immunotherapy with bacillus calmette-guérin for superficial bladder tumors.

OBJECTIVE: Intravesical immunotherapy with bacillus Calmette-Guérin (BCG) remains the most efficient modality for the treatment of carcinoma in situ and prevention of recurrences of Ta and T1 bladder tumors. Although elevations in a variety of urinary cytokines have been reported after BCG instillation, the mechanism by which BCG mediates antitumor activity has not been clearly established. Based upon our murine study, we reevaluated urinary cytokines before and after BCG instillations from the point of T helper (Th) 1/2 lymphocyte cytokine profiles. METHODS: Urinary interleukin (IL)-2, interferon (IFN)-gamma, IL-12, and IL-18 for Th1, and IL-4 for Th2 cytokines were measured by enzyme-linked immunosorbent assay just before and 4 h after the 4th or 5th instillation of 8 weekly instillations of 40-80 mg BCG, Tokyo strain, in 12 patients with superficial stages Ta and T1 bladder cancer, and carcinoma in situ. RESULTS: Two representative Th1 cytokines, IL-2 and IFN-gamma, significantly increased in urine after intravesical BCG instillations. Interestingly, IL-12, a strong inducer of Th1 cytokines, did not increase in the urine after BCG instillations. Instead, IL-18, that has recently been reported to induce IFN-gamma production in T and NK cells in synergy with IL-12, obviously elevated in urine after BCG instillations. Urinary IL-4, a representative of Th2 cytokines, did not change at all after intravesical BCG instillations. CONCLUSION: Our results clearly show the predominant importance of IL-18 followed by increases in Th1 cytokines, such as IL-2 and IFN-gamma, in the mechanisms of intravesical immunotherapy with BCG.

Efficacy of modest dose irradiation in combination with long-term endocrinal treatment for high-risk prostate cancer: a preliminary report.

BACKGROUND: Although radiotherapy in combination with endocrinal manipulation has been identified as an effective treatment for patients with high-risk prostate cancer, the optimal dose for locoregional control of prostate cancer in combination with hormonal therapy has not yet been determined. METHODS: The efficacy of modest doses of irradiation (60-62 Gy) combined with long-term endocrinal treatment for patients with high-risk prostate cancer (defined as a pretreatment prostate-specific antigen (PSA) level greater than 20 ng/ml or a Gleason's score of 8-10 or T3-T4 disease) was analyzed in 60 Japanese patients. The patients included in this study had received radical radiotherapy with long-term endocrinal manipulation in the period between 1993 and 2000. The median age of the patients was 70 years (range, 56-83). Neoadjuvant hormonal therapy with a median duration of 3.9 months was performed prior to radiotherapy, and hormonal therapy was continued until recurrence. A median dose of 61.4 Gy (range, 44-71.4) was delivered to the prostate. Pelvic node irradiation was performed in 49 patients (81.6%). RESULTS: After a median follow-up period of 28.5 months, the overall survival, cause-specific survival and biochemical relapse-free survival at 3 years were 94.4%, 96% and 89.8%, respectively. Local failure was observed in one patient, distant metastases were observed in three patients and a late toxic effect greater than Grade 2 was not observed in any patients. CONCLUSIONS: This study, though preliminary due to a short-term follow-up period, reveals the possibility that modest doses of irradiation combined with long-term endocrinal treatment could be an effective means of achieving excellent local control of high-risk prostate cancer.