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Tomohiko Ichikawa

Publications and source records attributed to Tomohiko Ichikawa.

At least 37 records · Page 2Linked to original sources
PubMed2005

Nucleotide variations in genes encoding plasminogen activator inhibitor-2 and serine proteinase inhibitor B10 associated with prostate cancer.

Genes encoding the serine proteinase inhibitor B family (SERPINBs) are mainly clustered on human chromosome 18 (18q21). Several serpins are known to affect malignant phenotypes of tumor cells, so aberrant genetic variants in this molecular family are candidates for conferring susceptibility for risk of cancer. We investigated whether eight selected non-synonymous variations within SERPINB loci at 18q21 might be associated with risk of prostate cancer in Japanese men. A case-control study involving 292 prostate-cancer patients and 384 controls revealed significant differences in regard to distribution of four missense variations in genes encoding plasminogen activator inhibitor 2 (PAI2) and SERPINB10. The most significant association was detected for the N120D polymorphism in the PAI2 gene (P = 5.0 x 10(-5)); men carrying the 120-N allele (120-N/N and 120-N/D genotypes) carried a 2.4-fold increased risk of prostate cancer (95% confidence interval 1.45-4.07). Associations were also detected for three other missense polymorphisms in those two genes. Strong linkage disequilibrium in the region encompassing PAI2 and SERPINB10 extended to about 50 kbp. The results suggested that missense variations in one or both of these genes confer important risks for prostate cancer, and may be themselves tumorigenic. Although confirmative replication studies on larger cohorts are awaited, clinical examination of these variations may become useful for identifying individuals at high risk for prostate cancer.

Alleles↗
PubMed2005

Loss of heterozygosity on chromosome 2 in Japanese patients with prostate cancer.

BACKGROUND: Loss of heterozygosity (LOH) on chromosome 2 is thought to occur only occasionally in prostate cancer (PCa), but allelic losses in this region are frequent in other types of human cancer, such as lung, thyroid, head and neck, and cervix. Here, we show a high-resolution deletion map of markers on chromosome 2 in Japanese patients with PCa. METHODS: Tissue samples were obtained from 66 patients with PCa. DNA from normal, tumor, or metastatic tissue was used as the template for polymerase chain reaction amplification for LOH using 24 microsatellite markers on human chromosome 2. RESULTS: Nineteen of the 66 cases (29%) showed LOH for at least one locus on chromosome 2. LOH on 2p was observed more frequently in cancer death cases than in organ confined and regional diseases (P < 0.001). Paired DNAs were available from both primary and metastatic tumors in the eight cases of cancer death; among those pairs, we detected LOH on 2p in four primary tumors, and in all metastatic foci (P < 0.05). Detailed deletion mapping in these tumors identified four distinct commonly deleted regions on 2p 16.3, 2p 12-cent, 2q 21.3, and 2q 23.1-2q 32.1. CONCLUSIONS: These results suggest that inactivation of putative tumor suppressor genes on chromosome 2 that may play an important role in the progression of Japanese patients with PCa.

Chromosome Mapping↗
PubMed2005

Changes in chromogranin a serum levels during endocrine therapy in metastatic prostate cancer patients.

INTRODUCTION: The concept of neuroendocrine (NE) differentiation in prostate cancer has become more widely recognized as its diagnostic, prognostic, and therapeutic usefulness. PATIENTS AND METHODS: We enrolled 38 patients with stage D prostate cancer who underwent endocrine therapy by medical or surgical castration and oral antiandrogen. According to PSA response, serum levels of CGA as a marker of NE differentiation were measured at the multiple points of time; (1) pre-treatment, (2) complete response (CR), (3) a nadir level of PSA, (4) PSA failure or hormone independent progression. We compared these serum values in relation to efficacy of endocrine therapy. RESULTS: There was no correlation between serum PSA and CGA values. Patients consisted of 27 with CR and 11 without CR. Serum CGA increased as intervals of endocrine therapy became longer with positive correlation (p < 0.05). Its velocity was higher in patients with PSA failure than in those without it (6.98 vs. 2.09 ng/ml/month, p = 0.011). CONCLUSION: During endocrine therapy in metastatic prostate cancer patients, serum CGA values were not related to serum PSA levels, and increased as treatment periods became longer. It is suggested that CGA velocity has potential to predict androgen independent progression after endocrine therapy.

Adenocarcinoma↗
PubMed2005

Up-regulation of the interferon gamma (IFN-gamma)-inducible chemokines IFN-inducible T-cell alpha chemoattractant and monokine induced by IFN-gamma and of their receptor CXC receptor 3 in human renal cell carcinoma.

BACKGROUND: The antiangiogenic CXC chemokines interferon gamma (IFN-gamma)-inducible T-cell alpha chemoattractant (I-TAC) and monokine induced by IFN-gamma (Mig) are known as members of IFN-gamma-inducible antiangiogenic CXC chemokines. However, the expression of these chemokines in highly angiogenic tumors remains poorly understood. The authors examined expression of I-TAC, Mig, and their receptor, CXCR3, in tissue samples from patients with renal cell carcinoma (RCC). METHODS: Twenty-one samples of untreated RCC and corresponding normal renal tissues were obtained from surgical specimens. The expression levels of I-TAC, Mig, and CXCR3 were investigated using reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, real-time RT-PCR analysis, and Western blot analysis. Immunohistochemistry was carried out to clarify the localization of both chemokines and of CXCR3. RESULTS: RT-PCR analysis showed strong expression levels of I-TAC, Mig, and CXCR3 in RCC tissues and very weak or undetectable expression in normal kidney tissues. Real-time RT-PCR analysis showed that expression levels of I-TAC, Mig, and CXCR3 in RCC tissues were 14.9 times greater, 30.3 times greater, and 9.9 times greater compared with the levels in the corresponding normal kidney tissues, respectively (P < 0.01). Western blot analysis showed up-regulation of I-TAC, Mig, and CXCR3 at the protein level. Immunofluorescence double stainings revealed that I-TAC coincided with pericytes and vascular smooth muscle cells (VSMCs) in tumor angiogenic vessels. Mig was detected in tumor endothelial cells (TECs) and in infiltrating leukocytes. In the corresponding normal kidney tissues, neither VSMCs nor endothelial cells showed positive stainings for these chemokines. CXCR3 was expressed in both tumor cells and infiltrating leukocytes. CONCLUSIONS: The results revealed special feature of vascular mural cells and TECs in RCC. The up-regulated I-TAC and Mig, produced by tumor vessels, may interact with CXCR3 expressed in tumor cells, with possible pathophysiologic significance in RCC progression.

Base Sequence↗
PubMed2005

Hormone treatment for prostate cancer: current issues and future directions.

Most prostate cancers are androgen-dependent and essentially respond to androgen ablation therapy. However, these tumors eventually become androgen-independent and progress despite androgen ablation. Since the androgen receptor (AR) sequence was determined, numerous studies have shown that AR plays a critical role in the development of androgen-refractory prostate cancer. Amplification of AR, mutations of AR, and deregulation of growth factors, cytokines and AR co-activators, which could be classified as AR-dependent pathways, are frequently observed in this condition. There are other pathways, AR-independent pathways that bypass AR, which involve neuroendocrine differentiation of prostate cancer cells, deregulation of apoptotic genes and unknown mechanisms related to down-regulation of AR. Androgen-refractory prostate cancers with the AR-dependent pathway could be treated by suppressing AR activity, whereas AR-independent tumors would require alternative management strategies. When more cell survival pathways are defined, improvement of patients' survival could be achieved by developing specific gene-targeting therapies that interfere with those pathways.

Androgen Antagonists↗
PubMed2005

Outcomes of shockwave lithotripsy for upper urinary-tract stones: a large-scale study at a single institution.

PURPOSE: We investigated the risk factors having an impact on the achievement of stone-free status and on the success rate, as well as on the likelihood of recurrence, in patients undergoing shockwave lithotripsy. PATIENTS AND METHODS: We evaluated the characteristics and outcomes of 3023 patients (3254 renal units) with upper urinary-tract stones who underwent SWL at the Funabashi Clinic over a 13-year period. We assessed the stone-free and success rates for 2844 patients (3061 renal units) 3 months post-SWL. We also determined the recurrence rate for the 1078 patients (1139 renal units) who had achieved stone-free status at that time. RESULTS: Overall, stone-free status was achieved in 65.1% of patients, and the success rate was 85.7%. There were significant differences in the stone-free rates depending on patient age, history of urolithiasis, and presence of pyuria before SWL, as well as the number, location, size, and composition of the stones. Stones recurred in 326 of 1139 renal units (28.6%) during a mean follow-up of 36 months. The recurrence rates were 7.5%, 24.1%, and 33.0% after 1, 3, 5 years, respectively. Multiple stones, a history of urolithiasis, and stones located in the kidney or both kidneys plus the ureter significantly influenced recurrence. Multivariate analysis demonstrated that multiple stones were most significantly related to recurrence. CONCLUSION: Treatment with SWL has a low morbidity and high effectiveness. The number and location of stones and a history of urolithiasis significantly influence recurrence. Further studies of prophylactic therapy are required, especially for patients with these factors.

Adolescent↗
PubMed2005

Efficacy and safety of laparoscopic surgery for pheochromocytoma.

OBJECTIVE: Laparoscopic surgery for primary aldosteronoma and Cushing's syndrome is well established. We report on our experiences with laparoscopic adrenalectomy for pheochromocytoma, and assess the efficacy and safety of the laparoscopic approach. METHODS: Between April 1998 and April 2003, a total of 23 patients underwent laparoscopic adrenalectomy for pheochromocytoma at Chiba University Hospital and Yokohama Rosai Hospital, Japan. We compared the surgical outcomes of these patients with those of 106 patients with adrenal tumors due to other pathologies who underwent laparoscopic adrenalectomy during the same period. RESULTS: The mean tumor size of pheochromocytoma was 4.96 cm. Mean operative time was 192.7 min, and mean estimated blood loss was 130 mL. Neither mean operative time nor mean estimated blood loss was greater for patients with pheochromocytoma. Intraoperative hypertension (systolic blood pressure > 180 mmHg) occurred in 39.1% (9/23) of patients with pheochromocytoma. During the follow-up period, there were no mortalities or recurrences of endocrinopathy. CONCLUSIONS: Laparoscopic adrenalectomy for pheochromocytoma is a safe and minimally invasive procedure.

Adrenal Gland Neoplasms↗
PubMed2005

Laparoscopic adrenalectomy in patients with large adrenal tumors.

OBJECTIVES: The maximum size of adrenal tumors that should be removed by laparoscopic adrenalectomy is controversial. We conducted a retrospective comparison of the results of laparoscopic adrenalectomy between patients with adrenal tumors > or =6 cm ('large tumors') and patients with adrenal tumors <6 cm ('small tumors'). METHODS: The participants in the study were 16 patients with large tumors and 111 patients with small tumors. The patients comprised 59 men and 68 women (mean age, 49.0 years; age range, 23-79) with varying diagnoses. Of the 16 patients with large tumors, five had Cushing's syndrome, four had pheochromocytomas, six had a non-functional tumor and one had malignant lymphoma. Adrenal tumors were confirmed by hormonal assays, biochemical tests and computed tomography. Of the 16 large tumors, five tumors were on the right and 11 were on the left. RESULTS: We found no significant differences in general demographic parameters between patients with large and small tumors. The mean duration of surgery was not significantly different between two groups. (large tumors, 210 min; small tumors,175 min). The mean volume of blood loss was 212 mL for large tumors and 30 mL for small tumors (P < 0.001, significant difference). There was no significant difference in time until walking, duration of hospitalization or number of using analgesics used. The time to first oral intake of group 1 (<6 cm) was significantly shorter than group 2 (> or =6 cm). Tumor size (> or =7.5 cm) was an independent predictor of a longer operation and greater blood loss in large tumors. CONCLUSIONS: Laparoscopic adrenalectomy for large tumors was safe and minimally invasive.

Adrenal Gland Neoplasms↗
PubMed2005

The prognostic value of p53, Ki-67 and matrix metalloproteinases MMP-2 and MMP-9 in transitional cell carcinoma of the renal pelvis and ureter.

AIM: To investigate the prognostic and predictive relevance of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 in patients with transitional cell carcinoma (TCC) of the upper urinary tract. METHODS: The expression of p53 protein, Ki-67 antigen, MMP-2 and MMP-9 was examined by immunohistochemistry in 69 patients with TCC of the upper urinary tract. Correlation of p53, Ki-67, MMP-2 and MMP-9 over-expression with conventional pathological parameters and patient survival was examined. RESULTS: p53 over-expression was significantly correlated with histological grade (P < 0.05), but not with pathological stage, vascular invasion, lymphatic invasion or lymph node metastasis. Ki-67 over-expression was significantly correlated with stage, grade, lymphatic invasion and vascular invasion (P < 0.05). In survival analyses, Ki-67 over-expression was a significant prognostic factor in the univariate analysis (P < 0.05), but it did not have a significant impact on survival in the multivariate analysis. Ki-67 labeling index was a significant prognostic factor in patients with a low p53 labeling index, but not in patients with a high p53 labeling index. CONCLUSION: Ki-67 over-expression is of prognostic value in TCC of the upper urinary tract, while p53, MMP-2 and MMP-9 are of limited value.

Adult↗
PubMed2005

[Molecular analysis for prostate cancer].

The molecular and biochemical mechanisms contributing to the development and progression of prostate carcinogenesis are still unknown. Recent technologies such as, real-time PCR, microarray, and laser capture microdissection, have accelerated the study of the molecular events involved in prostate cancer. The expression and function of numerous genes have been shown to be altered in prostate cancer. Such gene regulations are involved in cell cycle, signal transduction pathways, or gene expression. Analysis of the genes during prostate cancer progression has provided a better understanding of the basis of the disease. This review summarises current knowledge of the molecular analysis for prostate cancer.

Exons↗
PubMed2005

[New biomarkers for prostate cancer].

Prostate cancer is one of the most common cancers in Western men. In Japan, the incidence of this malignancy is increasing. Recent advances in molecular biology brought new biomarkers to prostate cancer diagnosis. In this article, we describe new biomarkers including serum and genetic and histochemical markers for screening, staging and drug selection for the management of prostate cancer patients.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2005

Transrectal high-intensity focused ultrasound in the treatment of localized prostate cancer: a multicenter study.

We report a multicenter trial with transrectal high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. A total of 72 consecutive patients with stage T1c-2NOM0 prostate cancer were treated using the Sonablate 500TM HIFU device (Focus Surgery, Indianapolis, USA). Biochemical recurrence was defined according to the criteria recommended by the American Society for Therapeutic Radiology and Oncology Consensus Panel. The median age and prostate specific antigen (PSA) level were 72 years and 8.10 ng/ml, respectively. The median follow-up period for all patients was 14.0 months. Biochemical disease-free survival rates in all patients at 1 and 2 years were 78% and 76%, respectively. Biochemical disease-free survival rates in patients with stage T1c, T2a and T2b groups at 2 years were 89, 67% and 40% (p = 0.0817). Biochemical disease-free survival rates in patients with Gleason scores of 2-4, 5-7 and 8-10 at 2 years were 88, 72% and 80% (p = 0.6539). Biochemical disease-free survival rates in patients with serum PSA of less than 10 ng/ml and 10-20 ng/ml were 75% and 78% (p = 0.6152). No viable tumor cells were noted in 68% of patients by postoperative prostate needle biopsy. Prostatic volume was decreased from 24.2 ml to 14.0 ml at 6 months after HIFU (p < 0.01). No statistically significant differences were noted in International Prostate Symptom Score, maximum urinary flow rate and quality of life analysis with Functional Assessment of Cancer Therapy. HIFU therapy appears to be minimally invasive, efficacious and safe for patients with localized prostate cancer with pretreatment PSA levels less than 20 ng/ml.

Adult↗
PubMed2004

Pretreatment serum testosterone level as a predictive factor of pathological stage in localized prostate cancer patients treated with radical prostatectomy.

OBJECTIVE: Pretreatment serum level of testosterone (T) is a potential prognostic factor for prostate cancer. The present study was conducted to evaluate the clinical significance of pretreatment serum T level in patients with clinically localized prostate cancer. MATERIALS AND METHODS: The subjects were 82 clinically localized prostate cancer patients treated with radical prostatectomy, whose pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment PSA or pathological Gleason score concerning the association with pathological stage and biochemical recurrence. RESULTS: The mean pretreatment T level was significantly lower in patients with non-organ-confined prostate cancer (pT3-T4, N1; 3.44+/-1.19 ng/ml) than in patients with organ-confined cancer (pT2; 4.33+/-1.42 ng/ml) (p=0.0078). Multivariate analysis demonstrated that pathological Gleason score, pretreatment serum T level and pretreatment PSA were significant predictors of extraprostatic disease. When the patients were divided into high and low T level groups according to the median value, pretreatment T levels were not significantly associated with PSA recurrence rates (p=0.7973). CONCLUSIONS: A lower pretreatment T level appears to be predictive of extraprostatic disease in patients with localized prostate cancer.

Age Factors↗
PubMed2004

CAG polymorphic repeat length in androgen receptor gene combined with pretreatment serum testosterone level as prognostic factor in patients with metastatic prostate cancer.

OBJECTIVE: Androgen ablation has been the initial treatment of choice for men with metastatic prostate cancer, but the disease generally relapses to an androgen-independent state thereafter. To understand which groups respond well or poorly to endocrine therapy is thus important. Several studies have shown that pretreatment serum testosterone (T) levels and the length of the CAG repeat at the N-terminal region of the androgen receptor are significant. However, the relevance of a combination of these factors has not been reported. We therefore investigated the clinical significance of CAG repeat length and pretreatment serum T levels among Japanese patients with metastatic prostate cancer (TxNxM1), and analyzed their relevance to survival. METHODS: Fifty-two Japanese patients with metastatic prostate cancer were enrolled in this study. We determined the length of the CAG repeat by both PCR sequencing and fragment analysis. Pretreatment serum T levels were measured using a radioimmunoassay. We examined the clinical significance of the CAG repeats and T levels individually and in combination with respect to several clinical factors. RESULTS: The pretreatment T level in the responder group was significantly higher than that in the non-responders (p=0.009) and the mean was 4.33+/-2.12 ng/ml. Kaplan-Meier analyses revealed that cause-specific survival was significantly enhanced in patients with higher levels of T (p=0.0489). The length of the CAG repeat was positively associated with age at diagnosis (p=0.032). The mean CAG repeat length was 22.5+/-3.0 and this value was significantly shorter in patients with poorly differentiated, than with well and moderately differentiated tumors (p=0.019). Kaplan-Meier analyses revealed a significantly better cause-specific survival rate as well as progression-free survival rate in patients with longer CAG repeats. Cause-specific survival curves were better in patients with higher T levels and longer CAG repeats than with lower T levels and shorter CAG repeats (p=0.0066). A multivariate analysis showed that the most significant prognostic factor was histological grade, followed by EOD grade, marker response and the combination of T and CAG. CONCLUSION: Pretreatment serum T levels together with the length of the N-terminal CAG repeat of the androgen receptor gene can distinguish responders from non-responders to androgen ablation. These parameters appear to be clinically useful, in that therapies appropriate to individual patients could be selected. Further studies are necessary to confirm these results.

Aged↗
PubMed2004

Clinical evaluation of transrectal power doppler imaging in the detection of prostate cancer.

To evaluate the clinical usefulness of power Doppler imaging (PDI), we compared this method to gray-scale transrectal ultrasound (TRUS) in the detection of prostate cancer. A total of 101 men with abnormally high serum prostate specific antigen (PSA) levels and/or abnormal digital rectal examination (DRE) findings were assessed using TRUS and PDI. Random systematic sextant and bilateral far lateral prostate biopsies were performed in all cases. In addition, when TRUS revealed a hypoechoic lesion or PDI revealed a hypervascular lesion (HVL), these lesions were directly biopsied. Of the 101 patients, 48 (47.5%), 42 (41.5%) and 42 (41.5%) were suspicious of having prostate cancer by DRE, TRUS and PDI, respectively. Prostate needle biopsy revealed prostate cancer in 39 patients (38.6%) and benign prostatic diseases in 62 patients (61.4%). If prostate needle biopsy was avoided when PDI was negative, then PDI eliminated the need for biopsy in 59 of the 101 patients (rate of biopsy procedures saved: 58.4%) and missed only 8 (13.6%) prostate cancers. Moreover, in 63 patients with intermediate PSA (3-10 ng/ml), the rate of biopsy procedures saved by DRE, TRUS, and PDI was 60.3%, 65.1%, and 68.3%, respectively, and the rate of cancers missed was 26.3%, 19.5%, and 14.0%, respectively. In a total of 826 specimens of TRUS-guided prostate biopsy, 126 (15.3%) specimens had adenocarcinoma. Site by site based analysis of the present series revealed 34.1% of prostate cancer sites were isoechoic and hypervascular. On a site by site basis, PDI had better sensitivity, specificity, positive predictive value and negative predictive value than TRUS. In 48 patients without abnormal DRE findings, on a site by site basis, the sensitivities of TRUS and PDI were 22.9% and 34.4%, respectively. Gleason score was associated with a positive rate of PDI on both a patient basis and site by site basis. From these results, on a patient basis, we conclude that PDI was helpful in the indication for prostate biopsy for all patients or patients with intermediate PSA level. On a site by site basis, PDI may be able to select prostate cancer sites at biopsy, in particular in patients without abnormal DRE findings.

Aged↗
PubMed2004

Vasopressin responsiveness of subclinical Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia.

OBJECTIVE: Vasopressin (AVP) is reported to be an important factor for regulating cortisol secretion in patients with Cushing's syndrome due to ACTH-independent macronodular adrenocortical hyperplasia (AIMAH). Recently, there have been several case reports of subclinical Cushing's syndrome due to AIMAH, in which the pathophysiological role of AVP has been unknown. The aim was to conduct an extensive investigation of AVP in the autonomous secretion of cortisol in subclinical Cushing's syndrome due to AIMAH. PATIENTS AND MEASUREMENTS: Five cases of AIMAH with subclinical Cushing's syndrome underwent prospective study including physical examination, imaging (MRI, CT and 131I-adosterol scintigraphy) and endocrinological evaluation that comprised basal plasma cortisol levels and urinary excretions of steroid metabolites, a dexamethasone suppression test and an AVP stimulation test. In case 1, left adrenalectomy was performed and the pathological diagnosis of AIMAH was established. An in vitro experiment using the cultured AIMAH adrenal cells was conducted to investigate cortisol secretion and expression of the V1-AVP receptor, mRNA by RT-PCR. RESULTS: All five cases were discovered incidentally to have bilateral adrenal nodules. Imaging by MRI and CT revealed large multinodular lesions in both adrenal glands, which showed positive uptake on 131I-adosterol scintigraphy. Although the basal values of plasma cortisol and urinary excretions of steroid metabolites were within normal limits, autonomous secretion of cortisol was assumed to occur because of lack of suppression during dexamethasone suppression. The five patients had no overt signs of Cushing's syndrome, and they were therefore diagnosed with subclinical Cushing's syndrome due to AIMAH. In all five patients, AVP stimulated cortisol secretion in vivo, whereas desmopressin acetate failed to affect cortisol secretion. In case 1, AVP stimulated cortisol secretion from cultured AIMAH adrenal cells, but this secretion had no relationship with cAMP production. In addition, over-expression of V1-AVP receptor mRNA in AIMAH tissue was determined by RT-PCR. CONCLUSION: Patients with subclinical Cushing's syndrome due to AIMAH commonly exhibit cortisol responsiveness to AVP, and this is probably mediated through activation of overexpressed V1-AVP receptors.

Adrenal Cortex↗
PubMed2004

Alternative antiandrogens to treat prostate cancer relapse after initial hormone therapy.

PURPOSE: We studied the efficiency of second or third line hormonal therapy for prostate cancer relapse after hormone therapy. MATERIALS AND METHODS: The study included 70 patients with advanced prostate cancer treated with hormonal therapy, androgen deprivation monotherapy or maximum androgen blockade including surgical or medical castration combined with steroidal antiandrogen, 100 mg chlormadinone acetate daily or nonsteroidal antiandrogens, 375 mg flutamide (FLT) daily or 80 mg bicalutamide (BCL) daily. When the disease relapsed, we discontinued the antiandrogen and evaluated the patient for the antiandrogen withdrawal syndrome (AWS). Thereafter we administrated an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of the AWS after first, second and third line hormonal therapy was 35.8%, 8.0% and 0%, respectively. The efficiency of subsequent hormonal therapy was not related to the occurrence of the AWS. Nonsteroidal antiandrogens as alternative therapies for disease relapse from primary therapy were effective in second line (FLT 38.1%, BCL 44.4%) or in third line (FLT 30.0%, BCL 28.6%) hormonal therapy. Of 5 (80%) patients who responded to second line therapy 4 (80%) had effective third line therapy, while only 1 of 12 (8.3%) second line nonresponders had effective third line therapy (p = 0.003). The survival of second line responders was significantly better than that of nonresponders (5-year survival rate 92.3% vs 23.9%, p <0.001), indicating a potential predictive value for second line responsiveness. No significant clinical factor identified second line responsiveness. CONCLUSIONS: Subsequent nonsteroidal antiandrogen therapies were effective against prostate cancer relapse after hormonal therapy. The response to third line therapy was more effective and survival was improved from the time of first line therapy relapse among second line responders than that in nonresponders. Our data support the notion that second line responders are androgen independent but still hormonally sensitive.

Aged↗