Prospective study on the relationship between clinical efficacy of secondary hormone therapy with flutamide and neuroendocrine differentiation in patients with relapsed prostate cancer after first line hormone therapy.

OBJECTIVE: The aim of this study was to prospectively verify the relationship between the clinical efficacies of secondary hormone therapy for castration-resistant prostate cancer (CRPC) following first line hormone therapy and neuroendocrine differentiation (NED). MATERIAL AND METHODS: Forty-six consecutive patients with CRPC following first line hormone therapy who were treated with flutamide as secondary hormone therapy were prospectively assessed with a median follow-up of 21 months. Serum chromogranin A (CgA), as a marker of NED, was measured using an immunoradiometric assay. RESULTS: Of the 46 patients, 22 (48%) responded to the secondary hormone therapy as a 50% or more reduction from baseline prostate-specific antigen (PSA) with a median response duration of 9.2 months. The PSA response group was correlated with significantly favorable cancer-specific survival (CSS) (92% vs 59% at 5 years, p = 0.0146) compared with the non-response group. Above-normal CgA levels at study entry were detected in 15 patients (33%), but no association with CSS was identified. Data on CgA kinetics were available in 35 patients. The CgA levels before and at 3 months during the treatment were similar. However, eight patients (23%) with an increase in CgA level of a quarter or more from baseline had a tendency for worse CSS (63% vs 84% at 5 years, p = 0.0507) compared with the remaining patients. CONCLUSION: Within limitations, in this study secondary hormone therapy with flutamide was effective for CRPC following first line hormone therapy. The above-normal CgA level in the first hormone resistance phase is mostly unrelated to prognosis. However, some patients with a remarkable increase in CgA in a short duration may have an unfavorable prognosis caused by NED as well.

Intravesical recurrence after surgical management of urothelial carcinoma of the upper urinary tract.

OBJECTIVES: To elucidate clinicopathological risk factors for intravesical recurrence (IVR) in patients undergoing nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC). METHODS: We identified a study population of 151 consecutive patients without previous or concurrent bladder cancer who underwent nephroureterectomy for UUT-UC. IVR was assessed in relation to tumor location, size, and multifocality, operation modality and time, stage, grade, lymphovascular invasion, regional lymph node metastasis, preoperative urinary cytology, and perioperative chemotherapy. The median follow-up time was 24 months. RESULTS: Of 151 patients, 51 (34%) developed IVR after nephroureterectomy, and 50 (98%) of the patients presented with IVR within 2 years. Tumor multifocality and site (located in ureter) were determined as risk factors for IVR by univariate analysis. In a multivariate analysis, only tumor multifocality (relative risk: 4.024, p = 0.001) was an independent predictor of IVR. Ten-year cancer-specific survival rates for the patients with and without IVR were 68 and 52%, respectively (p = 0.06). CONCLUSIONS: Tumor multifocality is a significant risk factor in developing IVR after surgery for UUT-UC. These results indicate that despite most IVR occurring within 2 years of treatment, it is necessary to follow such patients more closely using cystoscopy. However, IVR is unlikely to indicate a poorer prognosis.

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.