Efficacy and safety of abiraterone acetate plus prednisolone in patients with early metastatic castration-resistant prostate cancer who failed first-line androgen-deprivation therapy: a single-arm, phase 4 study.

AIM: The aim was to evaluate the efficacy and safety of abiraterone acetate plus prednisolone in patients with chemotherapy-naïve early metastatic castration-resistant prostate cancer who failed first-line androgen deprivation therapy. METHODS: Patients with early metastatic castration-resistant prostate cancer with confirmed prostate-specific antigen progression within 1-year or prostate-specific antigen progression without having normal prostate-specific antigen level (<4.0 ng/mL) during first-line androgen deprivation therapy were enrolled and administered abiraterone acetate (1000 mg) plus prednisolone (10 mg). A minimum of 48 patients were required according to Simon's minimax design. The primary endpoint was prostate-specific antigen response rate (≥50% prostate-specific antigen decline by 12 weeks), secondary endpoints included prostate-specific antigen progression-free survival and overall survival. Safety parameters were also assessed. RESULTS: For efficacy, 49/50 patients were evaluable. Median age was 73 (range: 55-86) years. The median duration of initial androgen deprivation therapy was 32.4 (range: 13.4-84.1) weeks and 48 patients experienced prostate-specific antigen progression within 1-year after initiation of androgen deprivation therapy. prostate-specific antigen response rate was 55.1% (95% confidence interval: 40.2%-69.3%), median prostate-specific antigen-progression-free survival was 24.1 weeks, and median overall survival was 102.9 weeks (95% confidence interval: 64.86 not estimable [NE]). Most common adverse event was nasopharyngitis (15/50 patients, 30.0%). The most common ≥grade 3 adverse event was alanine aminotransferase increased (6/50 patients, 12.0%). CONCLUSIONS: Abiraterone acetate plus prednisolone demonstrated a high prostate-specific antigen response rate of 55.1%, suggesting tumor growth still depends on androgen synthesis in patients with early metastatic castration-resistant prostate cancer. However, prostate-specific antigen-progression-free survival was shorter than that reported in previous studies. Considering the benefit-risk profile, abiraterone acetate plus prednisolone would be a beneficial treatment option for patients with chemotherapy-naive metastatic prostate cancer who show early castration resistance.

Impaired Delta Np63 expression associates with reduced beta-catenin and aggressive phenotypes of urothelial neoplasms.

p63, a homologue of the p53 gene, is considered to be essential for the normal development of stratified epithelia including urothelium. To examine possible roles of p63 in urothelial tumorigenesis, p63 expression was systematically examined in normal urothelium, low-grade papillary noninvasive (LPN) urothelial tumours, and high-grade or invasive carcinomas, using either an isoform-nonspecific or a Delta N-isoform-specific antibody. Expression profiles of p63 were also analysed in cultured cells. Immunoreactivity with the two antibodies was virtually identical in tissue samples examined. Basal and intermediate cell layers of normal urothelium showed intense nuclear p63 immunostaining. This normal staining pattern was preserved in a majority of LPN tumours, whereas it was frequently impaired in high-grade or muscle-invasive carcinomas. At the mRNA level, Delta Np63 expression predominated over TAp63, and amounts of Delta Np63 mRNA correlated with p63 immunoreactivity, confirming that Delta Np63 accounts for p63 expressed in urothelial tissues. In cultured cells, Delta Np63 was also expressed in low-grade tumour cells as well as normal urothelial cells, but undetectable in high-grade aggressive carcinoma cells. Interestingly, impaired Delta Np63 expression significantly associated with reduced beta-catenin expression that was possibly related to progression of urothelial neoplasms. Thus, impaired Delta Np63 expression characterises aggressive phenotypes of urothelial neoplasms.

RhoA is associated with invasion and lymph node metastasis in upper urinary tract cancer.

OBJECTIVE: To assess the roles of RhoA small GTPase (RhoA) in upper urinary tract cancer by analysing the mRNA and protein levels of RhoA. PATIENTS AND METHODS: The mRNA and protein levels of RhoA in matched sets of tumour, non-tumour and metastatic lymph node tissues of surgical specimens were analysed in 47 consecutive patients with renal pelvic/ureteric cancer, using the polymerase chain reaction after reverse transcription and Western blotting. The relationship between mRNA and protein levels of RhoA in tumour tissues and the clinicopathological features of the patients was also assessed. RESULTS: The mRNA levels of RhoA and RhoA protein were greater in tumour and metastatic lymph node tissues than in non-tumour tissues (all P < 0.001). The expression levels of RhoA mRNA and protein levels in primary tumours was related to poorly differentiated grade (both P < 0.05) and muscle invasion (P < 0.01 and < 0.001, respectively). Kaplan-Meier plots of survival in patients with low or high RhoA showed that high mRNA and protein levels were associated with a shorter disease-free (P < 0.01) and overall survival (P < 0.001). Multivariate analysis using the Cox proportional hazards model showed that a high RhoA protein level was an independent prognostic factor, second to stage, in disease-free and overall survival (both P < 0.05). CONCLUSIONS: These findings suggest that RhoA is involved in the invasion and metastasis of upper urinary tract cancer, indicating that RhoA may be a useful prognostic factor in this disease.

Successful treatment of metastatic adenocarcinoma of the urachus: report of 2 cases with more than 10-year survival.

Metastatic urachal cancer is often considered lethal. We report 2 cases of metastatic urachal carcinoma successfully treated with surgical excision followed by combinations of surgery, radiation, and chemotherapy against local recurrence and/or distant metastases, with a recurrence-free survival period of more than 10 years. These cases provide support for multimodal treatments of metastatic urachal cancer.

Suppression of spermatogenesis in ipsilateral and contralateral testicular tissues in patients with seminoma by human chorionic gonadotropin beta subunit.

OBJECTIVES: The pathologic complexity of the testicular tumor makes it difficult to demonstrate exactly the relationship between the impaired spermatogenesis in patients with a testicular tumor and the serum level of the human chorionic gonadotropin beta subunit (beta-hCG). Therefore, we performed quantitative evaluation of spermatogenesis in ipsilateral and contralateral testicular tissues of seminoma to simplify the relation pathologically and endocrinologically and to demonstrate the exact correlation between spermatogenesis and serum beta-hCG levels. METHODS: Fifty-three biopsy specimens from ipsilateral and contralateral testicular tissues of seminoma were analyzed histologically. The quantitative evaluation of spermatogenesis was performed by the mean Johnsen's score count (MJSC). Beta-hCG expression in seminoma was examined immunohistochemically. Serum beta-hCG, testosterone, estradiol, luteinizing hormone, and follicle-stimulating hormone levels were analyzed before orchiectomy. RESULTS: A significant linear relationship (r = -0.82; P <0.005) was found between the serum level of beta-hCG and the MJSC in contralateral testicular tissues but not in ipsilateral ones, although the suppression of spermatogenesis was observed in both sides without suppression of luteinizing hormone and/or follicle-stimulating hormone production. CONCLUSIONS: A clearcut fall in the MJSC with an associated rise in the serum level of beta-hCG was demonstrated in the contralateral testicular tissues but not in the ipsilateral ones of seminoma. It seems most likely that serum beta-hCG suppresses spermatogenesis in both ipsilateral and contralateral testicular tissues without the suppression occurring through the hypothalamus-pituitary-gonadal system, and also that some less well recognized factors affect spermatogenesis, making the relation between serum beta-hCG and MJSC obscure in ipsilateral testicular tissues.

Physician's attitudes towards disclosure of cancer diagnosis to elderly patients: a report from Tokyo, Japan.

Physicians' attitudes towards the disclosure of a cancer diagnosis to 114 consecutive patients (age range, 65-93 years; median 78 years) admitted to the Tokyo Metropolitan Tama Geriatric Hospital from April 1994 to May 1995 were analyzed utilizing a questionnaire administered to the attending physicians. Eighty-seven patients (76%) had been informed of their diagnosis before the initiation of cancer treatment, while 27 patients (24%) were not told. 'To carry out the treatment under patient's understanding' and 'consideration for patient's quality of life' were the major reasons for diagnosis disclosure, while 'lack of patient's ability to understand the information' and 'family's wish that the patient not be informed of the truth' were the major reasons for non-disclosure. Dementia, deteriorated performance status, and non-curability were major factors related to non-disclosure. Even with decisional ability, 15% of patients were not told their cancer diagnosis because wishes of their families were preferred. The current results suggest that telling cancer diagnosis to the elderly patients will not yield negative attitude of the patients and that there is no rationale for physicians to hesitate to disclose cancer diagnosis merely because of patient's high age.

Preoperative concurrent chemoradiotherapy against muscle-invasive bladder cancer: results of partial cystectomy in elderly or high-risk patients.

BACKGROUND: Good local control has been reported in cases of muscle-invasive bladder cancer treated by chemoradiotherapy and transurethral resection (TUR). However, definitive irradiation or extensive chemotherapy is often intolerable for elderly or poor-risk patients. We report here benefits of partial cystectomy after concurrent low-dose chemoradiotherapy for high-risk patients. METHODS: Thirty-seven patients with localized muscle-invasive bladder cancer (T2-T4) were treated with concurrent cisplatin (50-100 mg/body x 2 courses) and pelvic irradiation (40 Gy) preoperatively. Among 17 patients (46%) who achieved complete response (CR), 10 were not suitable for radical cystectomy and underwent partial cystectomy. Radical cystectomy was performed in 24 cases [CR = 6, partial response (PR) = 18]. Two patients (one CR and one PR) rejected open surgery and were treated by TUR of the primary site. One no change (NC) patient received no further treatment because of mental disorder. RESULTS: Median follow-up was 12 months (range 2-37 months). Fifteen of 36 evaluable cases (42%) achieved a pathological T0 response (no residual tumor). Estimated 3-year disease-free survival was 56% for all patients and 100% for T0 responders. Seven of 21 patients with pathological persistent tumor developed local recurrence (three patients) or distant metastasis (four patients). All of the 10 patients (eight with T0 response and two with a small residual tumor nest) who underwent partial cystectomy were recurrence-free for an observation period of up to 3 years. CONCLUSIONS: Bladder preservation by partial cystectomy may be a choice for patients who show a good response to preoperative chemoradiotherapy and are not suitable for radical cystectomy.

[Prostatic endometrioid carcinoma: a case report].

An 89-year-old man presented with urinary retention. Digital rectal examination was benign despite elevated serum prostate-specific antigen (PSA) level. Suprapubic prostatectomy was performed under the diagnosis of benign prostatic hyperplasia. Histopathological diagnosis was endometrioid carcinoma showing positive immunohistochemical staining for PSA. Postoperatively, estrogen was administered for 9 months. After 37 months, serum PSA level began to increase and a palpable nodule was detected on digital rectal examination. Biopsy showed coexistence of endometrioid carcinoma and acinar adenocarcinoma. Hormonal treatment was resumed and the disease has been well controlled for 65 months postoperatively.

[A case of renal cell carcinoma with solitary metastasis to the contralateral adrenal gland].

A 62-year-old female was admitted to our hospital with left flank pain and weight loss. Computerized tomography revealed a large left adrenal tumor and a small right renal tumor. A left adrenalectomy was performed initially to confirm sparing the left kidney. The left adrenal tumor weighed 650 g and was renal cell carcinoma histologically, suggesting a contralateral metastasis of the right renal tumor. Two months after the adrenalectomy, the right kidney was excised. The right adrenal gland was preserved. Pathologically, the renal tumor was also renal cell carcinoma. The patient has remained well for 34 months after the operation. The literature concerning the adrenal metastasis of renal cell carcinoma is briefly reviewed.

[Carcinoma of the renal pelvis and ureter following bladder carcinoma].

We followed 135 primary bladder carcinoma patients for at least 3 years. Subsequent carcinomas of the upper urinary tract were found in 5 patients (3.7 per cent) an average of 67 months after an initial treatment of the bladder tumors. Two patients underwent radical cystectomy and the remaining 3 patients received transurethral resections or partial cystectomy five to seven times for bladder lesions. Primary bladder tumor was multiple in all and one of them was accompanied by carcinoma in situ in the bladder and urethra. Except for one patient who presented with gross hematuria, four patients had no symptoms referable to the upper urinary tract tumor. However two of them had high stage disease. Positive urinary cytology was observed in only one patient. All patients underwent nephroureterectomy and the four got well but one died of acute heart failure. Regular urinary cytology and IVP should be done for an extended period of time for early detection of renal pelvic and ureter cancers in patients who had multiple and recurrent bladder cancers.