市川 智彦

The molecular mechanism playing a role in the development of benign prostate hypertrophy (BPH) and prostate cancer (PC) is not well defined. We performed microarray analysis to assess the gene expression change in BPH and PC, and performed network analysis. Normal prostate, BPH and PC tissues were obtained from patients who underwent an operation at Chiba University Hospital. Using Affymetrix Human Genome U133 Plus2.0 Array, we identified genes differentially expressed. The identified genes were analyzed using the Ingenuity Pathway Analysis (IPA) to investigate the functional network and gene ontology. The microarray analysis identified 402 genes in BPH and 141 genes in PC, which were up- or down-regulated at least 5.0-fold change in PC at all dose points. Analysis using IPA software revealed eight networks in BPH and five networks in PC. We narrowed these down to the top five genes, which were up- or down-regulated on the networks in their characteristic manner. From this new perspective, comparing BPH and PC in microarray studies, our data showing gene expression profiles provide candidate genes for better understanding of disease and new therapeutic targets.

Androgens are essential for prostatic growth and development, but also play a significant role in the pathogenesis of prostate disease. The traditional view that higher testosterone levels represent a risk factor for prostate cancer (PCa) appears to have little evidentiary support. Some studies have described a relationship between lower testosterone levels and more advanced disease. Serum androgen levels, within a broad range, are thus suggested to show no association with PCa risk, whereas low rather than high serum testosterone levels have been found to be associated with advanced or high-grade disease at the time of PCa diagnosis. Dihydrotestosterone, the principal prostatic androgen, is transformed from testosterone by type 1 and type 2 5alpha-reductase, and therapeutic benefits may thus be potentially achieved through the inhibition of 5alpha-reductase.

We present a case of retroperitoneal fibrosis (RPF) in a 72-year-old man who previously received pancreatectomy for autoimmune pancreatitis. He had received colectomy for early colon cancer on 11th November, 2005. During the routine follow-up for colon cancer, a swollen pancreas tail was detected on enhanced CT. He received distal pancreatectomy under the diagnosis of pancreas cancer on 4th October, 2007. Pathological diagnosis revealed the autoimmune pancreatitis. Eight months later, right hydronephrosis was observed in an abdominal ultrasonographic study, and at the same time, right hydroureterosis due to retroperitoneal soft tissue mass around the bifurcation was detected on enhanced CT. He was treated with predonisolone aiming at the diagnosis and/or therapy. Twelve weeks later, right hydronephrosis had disappeared and retroperitoneal mass had shrunken. Now, it is thought that autoimmune pancreatitis is a systemic sclerosing disease accompanied with extra-pancreatic pathologic changes such as RPF.

BACKGROUND: Limitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies. METHODOLOGY/PRINCIPAL FINDINGS: Floating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines. CONCLUSIONS/SIGNIFICANCE: The concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy.

OBJECTIVES: To evaluate changes in prostate volume (PV) and its association with selected urological measures and risk of surgical intervention in Japanese men with benign prostatic hyperplasia (BPH). METHODS: The medical records of all consecutive urologist-diagnosed BPH patients of >or=40 years old who attended any of four urology clinics in Japan during January 2004-June 2006 were reviewed. Both cross-sectional and longitudinal data were captured to analyze baseline correlations among urological measures, to evaluate the longitudinal changes in PV and selected urological measures, and to examine the predictors of surgical intervention. RESULTS: The follow-up period was 2.8 years. Mean PV and mean prostate-specific antigen (PSA) of 1331 eligible patients were 34.0 mL and 4.0 ng/mL, respectively. Both measures increased directly with age. Baseline PV correlated with residual urine volume (r = 0.18, P < 0.05) and PSA (r = 0.41, P < 0.001). Among 319 patients who had more than one PV measurement, PV increased in 51% of patients, remained the same in 28% and decreased in 21%. Use of alpha-blockers at baseline and during follow up was not associated with PV change. Patients who had a PV >or=30 mL, a severe International Prostate Symptom Score and a PSA level >or=1.5 ng/mL at baseline, were more likely to have surgical intervention during the follow-up period. CONCLUSIONS: Predictors generated in this study may help to identify a subset of BPH patients at high risk of surgical intervention.

Androgens play a central role in prostate cancer pathogenesis, and hence most of the patients respond to androgen deprivation therapies. However, patients tend to relapse with aggressive prostate cancer, which has been termed as hormone refractory. To identify the proteins that mediate progression to the hormone-refractory state, we used protein-chip technology for mass profiling of patients' sera. This study included 16 patients with metastatic hormone-refractory prostate cancer who were initially treated with androgen deprivation therapy. Serum samples were collected from each patient at five time points: point A, pre-treatment; point B, at the nadir of the prostate-specific antigen (PSA) level; point C, PSA failure; point D, the early hormone-refractory phase; and point E, the late hormone-refractory phase. Using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, we performed protein mass profiling of the patients' sera and identified a 6 640-Da peak that increased with disease progression. Target proteins were partially purified, and by amino acid sequencing the peak was identified as a fragment of apolipoprotein C-I (ApoC-I). Serum ApoC-I protein levels increased with disease progression. On immunohistochemical analysis, the ApoC-I protein was found localized to the cytoplasm of the hormone-refractory cancer cells. In this study, we showed an increase in serum ApoC-I protein levels in prostate cancer patients during their progression to the hormone-refractory state, which suggests that ApoC-I protein is related to progression of prostate cancer. However, as the exact role of ApoC-I in prostate cancer pathogenesis is unclear, further research is required.

OBJECTIVE: The aim of this study was to evaluate the efficacy and toxicities of the gemcitabine and paclitaxel combination regimen as second-line chemotherapy for patients with advanced or metastatic urothelial carcinoma (UC) who have previously been treated with platinum-based chemotherapy for the metastatic disease. METHODS: Thirty-three patients with advanced or metastatic UC who had received platinum-based chemotherapy were treated with an outpatient gemcitabine and paclitaxel combination regimen. A dose of 180 mg/m(2) paclitaxel was administered by intravenous (IV) infusion on Day 1, and 1000 mg/m(2) gemcitabine was administered by IV on Days 1, 8 and 15.The course was repeated every 28 days. Patients were evaluated after every 2 cycles of therapy using computed tomography. RESULTS: Of the 33 patients enrolled in this study, 30 could be evaluated to determine treatment efficacy; 10 had an objective response [overall response rate: 33.3%, 95% confidence interval (CI), 19.2-51.2%]. The median overall survival was 11.3 months (95% CI, 7.2-13.6 months). The chemotherapy sensitivity differed with disease site. The response rates of lung and bone metastases were 27% and 14%, and the progressive disease (PD) rates of lung and bone metastases were 13% and 14%, respectively. On the other hand, the response rate of liver metastasis was 14%, and its PD rate was 57%. None of the patients (n = 3) with adrenal metastasis responded to this regimen. Toxicities were mild, and no life-threatening complications occurred. CONCLUSIONS: Gemcitabine and paclitaxel combination therapy is a tolerable and active regimen for patients with advanced UC after failure of platinum-based chemotherapy.

The objective of this study was to perform external validation of a previously developed prostate biopsy nomogram (the CHIBA nomogram) and to compare it with previously published nomograms developed in Japanese and overseas populations. Two different cohorts of patients were used: one from the Chiba Cancer Center (n = 392) in which transperineal 16-core biopsy was performed, and another from Chibaken Saiseikai Narashino Hospital (n = 269) in which transrectal 16-core biopsy was carried out. All patients were Japanese men with serum prostate-specific antigen levels less than 10 ng/mL. The predictive accuracy of our CHIBA nomogram and of four other published nomograms (Finne's sextant biopsy-based logistic regression model, Karakiewicz's sextant biopsy-based nomogram, Chun's 10-core biopsy-based nomogram and Kawakami's three-dimensional biopsy-based nomogram) was quantified based on area under the curve derived from receiver operating characteristic curves. Head-to-head comparison of area under the curve values demonstrated that our nomogram was significantly more accurate than all other models except Chun's (P = 0.012 vs Finne's, P = 0.000 vs Karakiewicz's, and P = 0.003 vs Kawakami's). Our nomogram appears to be more useful for the Japanese population than Western models. Moreover, external validation demonstrates that its predictive accuracy does not vary according to biopsy approach. This is the first report to demonstrate that the predictive accuracy of a nomogram is independent from the biopsy method.

The relationships between serum level of testosterone (T) and prostate cancer (PCa) are complex. The present study evaluated whether presence of PCa alters serum T levels. Subjects were 125 patients with clinically localized PCa treated using radical prostatectomy (RP), for whom pretreatment T levels were recorded. We investigated clinical and pathological factors such as pretreatment serum T level, age, pretreatment prostate-specific antigen, Gleason score and pathological stage. Serum T and human luteinizing hormone (LH) levels before and after RP were then compared in 118 of the 125 patients. Mean pretreatment T level was significantly higher in patients with organ-confined PCa (pT2; 4.03 +/- 1.50 ng ml(-1)) than in patients with nonorgan-confined cancer (pT3; 3.42 +/- 1.06 ng ml(-1); P = 0.0438). No association existed between pretreatment serum T level and pathological Gleason score. After RP, serum T level (5.60 +/- 1.90 ng ml(-1)) was significantly elevated compared to preoperative level (3.89 +/- 1.43 ng ml(-1); P&lt;0.0001). In parallel, significant increases were seen in postoperative serum LH level (6.86 +/- 3.64 ng ml(-1)) compared to preoperative level (5.11 +/- 2.47 ng ml(-1)., P=0.0001). In contrast, differences in serum T levels according to pathological stage disappeared postoperatively (P = 0.5513). Significant increases in serum T and LH levels were seen after RP, compared to preoperative levels in parallel. This study suggests that serum T levels are altered by the presence of PCa, supporting the possibility that PCa may inhibit serum T levels with negative feedback in the hypothalamic-pituitary axis.

OBJECTIVES: Laparoscopic surgery is widely accepted for managing renal disease. Thus, the system used to educate and train novice surgeons in laparoscopic surgery becomes important to reduce the risks of surgery during their training. A prospective study was carried out to determine the usefulness of using panoramic views during laparoscopic surgery. METHODS: Between April 2004 and March 2007, four novice surgeons started learning laparoscopic radical nephrectomy: two carried out surgery without panoramic views and two used panoramic views. Operating time and blood loss for the initial 10 cases of each surgeon were compared. Panoramic views were obtained by interlacing each video frame of the video images electronically; the images were then processed and displayed during each step of laparoscopic surgery. RESULTS: Panoramic, real-time views could be obtained, and they served as navigation maps. The learning curve of surgeons using the panoramic views was shorter than that of surgeons who did not use panoramic views. Time to ligation of renal artery from port placement and the operating time was shorter (69.0 +/- 21.5 min vs 106.8 +/- 44.9 min, P = 0.0016, 212 +/- 42 min vs 254 +/- 46 min, P = 0.0489, respectively) and the estimated blood loss was less for the surgeons who used panoramic views (87 +/- 109 mL vs 334 +/- 268 mL, P = 0.0005). CONCLUSION: Panoramic views during laparoscopic surgery shortened operating time and reduced blood loss, indicating their usefulness in assisting novice surgeons to carry out procedures safely and accurately.

In the last decade, abundant evidence has suggested that the insulin-like growth factor (IGF) family comprises a multi-component network of molecules involved in the regulation of both physiological and pathological growth processes in the prostate. The IGF axis plays an important role in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicate that circulating IGF-I levels are positively associated with increased risk of prostate cancer. Activation of IGF-I receptor (IGF-IR) by IGF-I has mitogenic and anti-apoptotic effects on normal and malignant prostate cells. Therapeutic alternatives in men with progressive prostate cancer after androgen ablation are very limited and more effective therapies are needed for such patients. Inactivation of the IGF-I axis represents a potential target to treat androgen-independent prostate cancer. This review addresses epidemiological studies of IGF-I and therapeutic strategies including reduction of IGF-I levels, inhibition of IGF-IR and the signaling mechanisms involved.

The heterodimeric complex composed of rBAT (related to b(0,+) amino acid transporter), a single-membrane-spanning glycosylated heavy chain, and b(0,+)AT, a putative 12-membrane-spanning non-glycosylated light chain, is an amino acid transporter that mediates the activity of system b(0,+), a major apical transport system for cystine and dibasic amino acids in renal proximal tubule and small intestine. The C-terminus of b(0,+)AT has been proposed to play an important role in the functional expression of the heterodimeric transporters. In the present study, to reveal the roles of the C-terminus, we analysed b(0,+)AT mutants whose C-termini were sequentially deleted or replaced by site-directed mutagenesis in polarized MDCKII (Madin-Darby canine kidney II), non-polarized HEK-293 (human embryonic kidney-293) and HeLa cells. Although the deletion of C-terminus of b(0,+)AT did not affect the formation of a heterodimer with rBAT, it resulted in the loss of apparent transport function, owing to the failure of the plasma-membrane targeting of rBAT-b(0,+)AT heterodimeric complex associated with incomplete glycosylation of rBAT. A motif-like sequence Val(480)-Pro(481)-Pro(482) was identified in the C-terminus of b(0,+)AT to be responsible for the C-terminus action in promoting the trafficking of rBAT-b(0,+)AT heterodimeric complex from the ER (endoplasmic reticulum) to Golgi apparatus. This is, to our knowledge, the first demonstration of the active contribution of the C-terminus of a light-chain subunit to the intracellular trafficking of heterodimeric transporters. Because the motif-like sequence Val(480)-Pro(481)-Pro(482) is well conserved among the C-termini of light-chain subunits, common regulatory mechanisms could be proposed among heterodimeric amino acid transporters.

Neuroendocrine (NE) cells originally exist in the normal prostate acini and duct, regulating prostatic growth, differentiation and secretion. Clusters of malignant NE cells are found in most prostate cancer (PCa) cases. NE differentiation (NED) is the basic character of the prostate, either benign or malignant. NE cells hold certain peptide hormones or pro-hormones, which affect the target cells by endocrine, paracrine, autocrine and neuroendocrine transmission in an androgen-independent fashion due to the lack of androgen receptor. NED is accessed by immunohistochemical staining or measurement of serum levels of NE markers. The extent of NED is associated with progression and prognosis of PCa. Chromogranin A (CGA) is the most important NE marker. In metastatic PCa, pretreatment serum CGA levels can be a predictor for progression and survival after endocrine therapy. It is recommended to measure longitudinal change in serum CGA. The NE pathway can also be a therapeutic target.

Our objective was to determine the incidence of inguinal hernia (IH) after surgery for prostatic diseases. Medical records of 395 patients who underwent radical retropubic prostatectomy (RRP; n = 155), open simple prostatectomy (OP; n = 35), or transurethral resection of the prostate (TURP; n = 205) at the Chibaken Saiseikai Narashino Hospital from April 2000 to March 2007 were retrospectively evaluated. The incidence of IH was 23.9% in the RRP group, 18.9% in the OP group, and 2% in the TURP group. Overall, 91.9% in the RRP and 83.3% in the OP group developed an IH within 2 years postoperatively. The laterality of IH after open surgery was mainly on the right side. Subclinical IH were seen in 25% of RRP cases. The existence of subclinical IH was the only significant risk factor for postoperative IH in this analysis. Furthermore, OP and RRP procedures significantly increased the risk of postoperative IH compared with TURP. The hernia-free ratios were significantly lower after RRP and OP than after TURP (vs RRP: P < 0.001; vs OP: P < 0.001). Our findings confirm that a lower abdominal incision itself is associated with postoperative IH in patients undergoing prostate surgery. Attention must be paid to pre-existing subclinical IH through careful preoperative assessment. Patients should be followed for more than 2 years due to the high incidence of postoperative IH.

BACKGROUND: Prostate cancer is often multifocal and shows histological heterogeneity among different tumor foci within the same prostate. We analyzed the origin and molecular basis of multifocal prostate cancer and genomic alterations associated with tumor progression. METHODS: We examined 45 multifocal prostate cancer foci from 22 radical prostatectomy specimens by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. RESULTS: Frequent chromosomal alternations were losses of 2q21-24 (22.2%), 6q14-22 (60.0%), 8p12-22 (35.6%), 13q14-31 (44.4%) and 16q13-24 (24.4%) and gains of 8q21.3-24.3 (37.8%) and 7q21-33 (20.0%). Frequency of losses of 8p12-22 and 16q13-24 and gains of 8q21.3-24.3 were significantly higher in tumors with high Gleason score (GS) than in those with low GS (P < 0.01, P < 0.05, and P < 0.01, respectively). Tumors with losses of 8p12-22 or 13q14-31 displayed larger volume than those without such losses (P < 0.05 and P < 0.01, respectively). In comparison between different tumor foci within the same prostate, chromosomal alterations did not show completely the same pattern between any tumor foci, except for one case in which two of the three foci displayed no chromosomal abnormalities. More malignant tumors (high GS or extracapsular invasion) displayed significantly higher frequency of losses of 8p12-22 (P < 0.05). CONCLUSIONS: These results suggest that tumor foci within the same prostate represent independent tumors with differing clonal origin and that loss of 8p12-22 represents an important determinant of prostate cancer progression.

Renal cell carcinoma (RCC) is capable of metastasizing to several organs. Synchronous isolated contralateral adrenal metastasis of the primary RCC is, however, very rare. Herein we report a case of RCC with a huge solitary metastasis to the contralateral adrenal gland that was surgically treated. We scheduled nephrectomy for the left primary RCC and adrenalectomy for the right adrenal tumor. However, at surgery we found a huge right adrenal tumor that had invaded the right kidney, right renal vein, and inferior vena cava. Therefore right nephrectomy was performed simultaneously with resection and reconstruction of the inferior vena cava. Pathological findings demonstrated that the left renal tumor and right adrenal tumor had the same histology. Although the patient required hemodialysis, he remains well at six months postoperatively. So far, there have been only two cases of a solitary contralateral metastatic adrenal tumor that was larger than the primary RCC, thus the present case is the third one.

A 69-year-old woman presented with macroscopic hematuria and severe anemia. Cystoscopy revealed flat edematous mucosa with continuous bleeding. Transurethral coagulation and a biopsy of the urinary bladder were performed. Histopathological examination of the biopsy revealed non-Hodgkin's lymphoma of the mucosa-associated lymphoid tissue (MALT) type. Results of a computed tomography scan and gallium scintigraphy suggested that it was a primary malignant lymphoma of the urinary bladder. A urinary tract infection was found and she was treated with antibiotics for 2 weeks. Because of the detection of a Helicobacter pylori (HP) infection in the gastric mucosal biopsy specimens, the patient was subsequently administered HP eradication therapy. Consequently, the lymphoma disappeared and the woman has had no tumor recurrence for the past 25 months.

Testicular involvement by sarcoidosis is a rare condition. A 23-year-old Japanese man had asymptomatic bilateral testicular lesions, which were detected by gallium scintigram, together with lesions located bilaterally in the uvea, lungs and hilar, and mediastinal lymph nodes and unilateral supraclavicular lymph nodes. Semen analysis demonstrated severely impaired spermatogenesis. Treatment with corticosteroid dramatically improved these lesions and restored spermatogenesis. This case report suggests that testicular sarcoidosis may cause male infertility.

Background: GNAS1 encodes the a-subunit of the G(s) protein (G(s alpha) which binds GTP and stimulates adenylyl cyclase. Activating mutations lead to somatotroph, thyroid, adrenal and gonadal adenomas or the McCune-Albright syndrome and recently the T399C polymorphism in GNAS1 has been reported to be associated with malignancies. The purpose of the present case-control study with 349 Japanese prostate cancer patients and 203 urological controls was to determine whether the GNAS1 T393C polymorphism is associated with prostate cancer risk. Materials and Methods: The GNAS1 T393C polymorphism was examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Odds ratios (OR) were adjusted for age using multiple logistic regression analysis with SPSS Medical Pack. Results: The allele frequencies were compatible with the control population in Hardy-Weinberg equilibrium with 80, 169 and 100 for GNAS1 C/C, C/T and TIT, respectively in the patients with prostate cancer, compared with 42, 94 and 67 in the controls. No association between the GNAS1 polymorphism and prostate cancer risk was apparent. The C/C genotype was more frequent among the prostate cancer patients (22.9%) than the controls (20.7%), although without significance (OR, 1.30; 95% CI, 0.80-2.12; p=0.29). Conclusion: This pilot stud), does not support involvement of the GNAS1 polymorphism in prostate cancer risk.

Prostate cancer is androgen-dependent, and hormone therapy, mainly achieved by androgen deprivation, has been one of the main treatment modalities in the clinical management of prostate cancer patients for more than six decades. In the 1980s, luteinizing hormone-releasing hormone agonists, which reduce testosterone to castration levels, were introduced Also, after the 1980s, nonsteroidal antiandrogens were developed in addition to steroidal antiandrogens. Since then, so-called maximum androgen blockade (MAB)/combined androgen blockade (CAB), which is a combination of surgical or medical castration and oral antiandrogens, has been developed. More recently, novel treatment modalities have been developed, such as intermittent androgen suppression, nonsteroidal antiandrogen monotherapy, and alternative antiandrogen therapy after relapse from initial MAB/CAB, The present article focuses on these treatment modalities to review current topics and perspectives with respect to hormone therapy for prostate cancer.

Prostate-specific antigen (PSA) screening has led to a remarkable increase in prostate cancer cases undergoing operative therapy. Over half of patients with locally advanced cancer (&gt;= pT3) develop rising PSA levels (biochemical failure) within 10 years. It is very difficult to predict which patients will progress rapidly to advanced disease following biochemical failure (BF). Therefore, a more useful prognostic factor is needed to suggest the most appropriate therapies for each patient. To determine chromosomal aberrations, we examined 30 patients with stage pT2 or pT3 primary prostate adenocarcinomas and no metastases (pN0M0) by comparative genomic hybridization (CGH). Laser capture microdissection (LCM) was used to gather cancer cells from frozen prostate specimens. Common chromosomal alterations included losses on 2q23-24, 4q26-28, 6q14-22, 8p12-22 and 13q21-31, as well as gains on 1p32-36, 6p21 and 17q21-22. Losses at 8p12-22 and 13q21-31 were observed more frequently in pT3 than pT2 tumors (P&lt;0.05 and P&lt;0.01, respectively). Losses at 8p12-22 were more frequent in tumors with BF (P&lt;0.05), and those at 13q12-21 were more frequent in tumors with Gleason score (GS) 7 or more than lower GS (P&lt;0.05). These findings suggest that losses of 8p12-22 and 13q21-31 are important determinants of prostate cancer progression.

PURPOSE: Large meta-analyses have documented that maximum androgen blockade with nonsteroidal antiandrogens for advanced prostate cancer confers survival benefits, although it remains controversial. Also, we and others have reported the effectiveness of second line hormonal therapy for prostate cancer that relapses after initial hormone therapy. However, there is little clinical evidence of the effectiveness of the latter treatment strategy. Therefore, in this multicenter trial in Japan we analyzed clinical outcomes following alternative changing from 1 nonsteroidal antiandrogen to another, ie bicalutamide to flutamide and flutamide to bicalutamide, for advanced prostate cancer that relapsed after initial maximum androgen blockade. MATERIALS AND METHODS: The study included 232 patients with advanced prostate cancer who were initially treated with maximum androgen blockade, including surgical or medical castration combined with nonsteroidal antiandrogens. If a patient relapsed while on first line therapy, we discontinued antiandrogen and evaluated the patient for antiandrogen withdrawal syndrome. We then administered an alternative antiandrogen and evaluated its effect. RESULTS: The incidence of antiandrogen withdrawal syndrome after initial maximum androgen blockade was 15.5% for bicalutamide and 12.8% for flutamide. A prostate specific antigen decrease after antiandrogen withdrawal was a prognostic factor. Nonsteroidal antiandrogens as alternative therapy in patients with relapse after the initial maximum androgen blockade were effective (prostate specific antigen decrease greater than 50%) as second line maximum androgen blockade. Of 232 patients 142 (61.2%) showed a prostate specific antigen decrease in response to an alternative antiandrogen. These responders had significantly better survival than nonresponders, suggesting that responsiveness to second line therapy predicts increased survival. CONCLUSIONS: Following maximum androgen blockade with an alternative nonsteroidal antiandrogen is effective for advanced prostate cancer that has relapsed after initial maximum androgen blockade. Even a partial response to second line maximum androgen blockade was associated with improved survival. Our data support the notion that responders to second line regimens are androgen independent but still hormonally sensitive.