Takahiko Hachiya

Long-term results of a randomized trial for the treatment of stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities

OBJECTIVES To improve the treatment of locally advanced prostate cancer (Stages B2 and C), a prospective randomized trial was conducted to compare radical prostatectomy versus external beam radiotherapy with the combination of endocrine therapy in both modalities. METHODS One hundred patients were enrolled and 95 were evaluated. Forty-six patients underwent radical prostatectomy with pelvic lymph node dissection, and 49 were treated with radiation by linear accelerator with 40 to 50 Gy to the whole pelvis and a 20-Gy boost to the prostatic area. For all patients, endocrine therapy was initiated 8 weeks before surgery or radiation, and continued thereafter. The living patients were asked to respond to a quality-of-life questionnaire. RESULTS The follow-up period ranged from 6.0 to 94.4 months (median 58.5). The progression-free and cause-specific survival rates at 5 years were 90.5% and 96.6% in the surgery group and 81.2% and 84.6% in the radiation group, respectively. The surgery group had better progression-free and cause-specific survival rates (P = 0.044 and 0.024, respectively). More patients in the surgery group complained of urinary incontinence. The questionnaire revealed that quality of life was less disturbed in the radiation group. CONCLUSIONS Radical prostatectomy combined with endocrine therapy may contribute to the survival benefit of patients with locally advanced prostate cancer. External beam radiotherapy in combination with endocrine therapy can be used in selected patients because of its low morbidity.

Fluorescence in situ hybridization analysis of c-myc amplification in stage T3N0M0 prostate cancer in Japanese patients

Objective:  Genetic aberration such as the amplification of c‐myc has been commonly found in advanced prostate cancer. The aim of this study was to elucidate chromosome 8 alteration, including a gain and amplification of 8q24 (c‐myc gene), related to the progression and survival in advanced (Stage C) prostate cancer.

Androgen deprivation prior to radical prostatectomy for T2b and T3 prostate cancer

OBJECTIVE In an effort to improve on the results of radical prostatectomy for clinical stages T2b and T3 prostate cancer, a selected group of patients received androgen deprivation for three to sixteen months prior to surgery. METHODS Fifteen men with clinical T2b and 22 with small T3 tumors received a luteinizing hormone-releasing hormone analog (n = 34) or a bilateral orchiectomy (n = 3) three to sixteen months prior to radical retropubic prostatectomy. The prostate was evaluated with particular attention to tumor grade, presence of extracapsular extension, tumor at the inked margin, seminal vesicle invasion, and tumor in the lymph nodes. RESULTS No patient had clinical or chemical (prostate-specific antigen [PSA]) progression during androgen deprivation. The PSA level declined a mean 90 percent and remained above 4 ng/mL in only two patients. The prostate volume decreased an estimated 30-50 percent. Prostate cancer at the inked margin was found in 15 (41%) and seminal vesicle involvement in 11 (30%) patients. Five (14%) had tumor in regional lymph nodes. There was no difference in regard to positive margins or lymph node metastases between those clinically staged as T2b and those preoperatively staged as T3. Fourteen patients have received adjuvant therapy (13 androgen deprivation, one radiation therapy). None has progressed (mean follow-up, 38.4 months). Of 23 who did not receive immediate additional therapy, six (26%) had progression, as was evident from an increase in PSA and have since been treated. Only one continued to progress. Thirty-five of the 37 patients are alive. Seventeen (46%) are tumor free (PSA < 0.4 ng/mL) without further androgen deprivation. CONCLUSIONS Only a prospective randomized trial can determine whether androgen deprivation prior to radical prostatectomy has a role. The results from this trial are encouraging for several reasons. The prostate is much smaller as a result of androgen deprivation and this may facilitate surgery. Although the great majority of these patients were expected to be margin positive, 60 percent had negative margins and only 14 percent had positive lymph nodes.

Prospective Study of Estramustine Phosphate for Hormone Refractory Prostate Cancer Patients following Androgen Deprivation Therapy

Introduction: Estramustine phosphate (EMP) in combination with other cytotoxic agents has been widely used in clinical trials as an anti-tumor agent for the treatment of hormone-refractory prostate cancer (HRPC). However, few prospective studies have considered the efficacy of EMP monotherapy for HRPC patients following androgen-deprivation therapy (ADT), given the availability of methods to measure prostate-specific antigen (PSA) levels in the serum. We therefore initiated a prospective study to determine whether EMP is efficient for HRPC following ADT using changes in PSA levels as the major endpoint. Methods: After a diagnosis of anti-androgen withdrawal syndrome had been excluded, 34 patients with HRPC who showed an elevated serum PSA level in 3 or more sequential tests following ADT were treated orally with 560 mg/day of EMP. The clinical stage and the median PSA value for inclusion in the study were D2 and 25.9 (range 6.5–540.8) ng/ml, respectively. Treatment was continued until evidence of disease progression reappeared or until severe adverse effects appeared. Results: Of the 34 patients enrolled, 29 were evaluated, while the other 5 (15%) patients were discontinued due to severe gastrointestinal side effects. Seven of the 29 patients (24%) showed a decrease of 50% or greater in serum PSA levels from the initially elevated values, with the median duration of PSA response being 8.0 (range 2.2–18.8) months. Baseline PSA, hemoglobin, alkaline phosphatase, lactate dehydrogenase, performance status, and length of time of initial hormonal treatment did not correlate with the PSA response. With a median follow-up time of 20.0 (range 3.2–45.6) months, the cancer-specific survival rate at 2 years was 83% in the PSA responders and 44% in the non-responders. The PSA response was correlated with cancer-specific survival (p = 0.029). Conclusions: Following ADT one quarter of HRPC patients responded to EMP, with more than 50% of patients showing a decrease in PSA levels and an enhanced survival rate.

Adenoid cystic carcinoma of the prostate: A case report with immunohistochemical and in situ hybridization staining for prostate-specific antigen

Abstract A 43‐year‐old man with urinary outlet obstruction was referred to our hospital. A digital rectal examination revealed an elastic hard prostate. The serum prostate‐specific antigen (PSA), serum prostatic acid phosphate and γ‐seminoprotein levels were found to be within the normal range, and transrectal ultrasound sonography provided normal findings. The patient underwent a subcapsular prostatectomy under a diagnosis of benign prostatic hyperplasia. Histopathologically, the lesion was diagnosed as an adenoid cystic carcinoma of the prostate. Because a further examination revealed a pathologic extension into the urinary bladder, a radical cystoprostatectomy was performed. The expression of PSA protein and PSA mRNA was studied by means of immunohistochemistry and an in situ hybridization technique. The adenoid cystic carcinoma in the patient did not show any positive signs for PSA protein or PSA mRNA.

Silodosin versus naftopidil for the treatment of benign prostatic hyperplasia: A multicenter randomized trial

This was a multicenter randomized trial to investigate the clinical efficacy and the impact on sexual function of alpha‐1A selective silodosin and alpha‐1D selective naftopidil for treatment of benign prostatic hyperplasia. A total of 97 patients with lower urinary tract symptoms/benign prostatic hyperplasia who had an International Prostate Symptom Score of 8 or more were randomly assigned to receive silodosin (8 mg/day, n = 53) or naftopidil (75 mg/day, n = 44). Before and 4, 8 and 12 weeks after treatment, International Prostate Symptom Score and its quality of life score were used to assess lower urinary tract symptoms. Also, International Index of Erectile Function‐5, and an original questionnaire were used to evaluate erectile function and ejaculation for sexually active patients, respectively. The silodosin group showed advantages in terms of voiding symptoms and quality of life of International Prostate Symptom Score when compared with the naftopidil group. Both silodosin and naftopidil showed no significant effect on International Index of Erectile Function‐5. A total of 23 sexually active patients in the silodosin group experienced more ejaculatory impairment than 21 patients in the naftopidil group, with a decrease of ejaculation volume (87% vs 40%, P = 0.003), prolonged time to ejaculation (56% vs 33%, P = 0.027) and decrease of orgasm (50% vs 39%, P = 0.027). These results suggest that alpha‐1A selective blockers are more effective for voiding symptoms, whereas alpha‐1D selective blockers offer a minor degree of ejaculatory dysfunction.

Immunohistochemical and Ultrastructural Features of Neuroendocrine Differentiated Carcinomas of the Prostate: An Immunoelectron Microscopic Study

The purpose of this study was to further define the immunohistochemical and ultrastructural characteristics of neuroendocrine (NE) differentiated prostatic carcinomas. Seventy-seven specimens were obtained from prostatic carcinoma tumors during prostatectomy, transurethral resection of prostate or biopsy in 77 prostate cancer patients, and analyzed by immunohistochemical staining for chromogranin A (CgA). Nine of these tumors were also studied by elctron microscopy and 4 were examined by pre-embedding immunoelectron microscopy. CgA-stained cells were detected in 36 tumors (47%). Clinically advanced tumors or tumors with higher histological grades were associated with increased NE differentiation. Three of the tumors studied by electron microscopy contained cells showing unequivocal NE differentiation revealed by the presence of neurosecretory granules, while the poorly NE-differentiated malignant cells contained pleomorphic granules, which were lysosomal-like rather than NE-type granules. Immunoelectron microscopy demonstrated the presence of CgA immunoreactivity on the pleomorphic granules in the poorly differentiated malignant glands. This study suggests that NE-differentiated malignant cells in prostate cancer tissues may induce aggressive behavior in adjacent proliferating neoplastic cells via a paracrine mechanism.

A retrospective study of the treatment of locally advanced prostate cancer by six institutions in eastern and north-eastern Japan

To investigate patients with locally advanced prostate cancer treated at six academic institutions in eastern and north‐eastern Japan from 1988 to 2000, to facilitate the establishment of Japanese guidelines for the diagnosis and treatment of locally advanced prostate cancer.

Significance of the BTA Test in Bladder Cancer: A Multicenter Trial

Background:

Implications of circulating chromogranin A in prostate cancer

Objective. To evaluate whether measurement of circulating chromogranin A (CgA) levels provides clinicopathological and prognostic information in prostate cancer. Material and methods. Plasma CgA levels were measured in 57 patients with histologically confirmed prostate cancer (stage B or less, n=22; stage C, n=10; stage D1, n=2; hormone-naive D2, n=12; hormone-refractory D2, n=11) and in 22 with undetected prostate cancer using an enzyme-linked immunoabsorbent assay. Results. Median plasma CgA levels were significantly higher in patients with prostate cancer than in those with undetected cancer (p=0.0271). Higher stage (p<0.0001) and higher grade (p=0.0412) tumours were also significantly associated with higher plasma CgA levels. Above-normal CgA levels were also detected in 4/27 patients (15%) who underwent radical prostatectomy. Postoperative clinical failure was not reported in the prostatectomy patients; however, prostate-specific antigen (PSA) failure was reported in 44% of patients after a median follow-up period of 20.3 months. Multivariate analysis revealed that the pathological stage of the tumour was the only independent predictive variable for postoperative PSA failure (p=0.0494). Preoperative plasma CgA levels had no impact on postoperative PSA failure in the subgroup (prostatectomy patients). Elevated plasma CgA levels were associated with a poor survival prognosis in patients with stage D2 prostate cancer after a median follow-up period of 22.5 months (p=0.0416). Conclusions. It was demonstrated in this study that plasma CgA levels in prostate cancer increase with the severity of the disease, especially for progressive hormone-refractory prostate cancer (HRPC), after hormone therapy. Although this cross-sectional study involved only a small number of patients, we believe that plasma CgA levels may effectively predict HRPC status and prognosis in metastatic cases.