Racial variation in CAG repeat lengths within the androgen receptor gene among prostate cancer patients of lower socioeconomic status.

PURPOSE: To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis; (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men. METHODS: CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The chi(2) test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis. RESULTS: The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels >/= 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P =.001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P =.09) but were not more likely to have a higher PSA concentration or Gleason score. CONCLUSION: In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings.     

Long-term oncologic results of salvage radical prostatectomy for locally recurrent prostate cancer after radiotherapy

PURPOSE: Salvage radical prostatectomy (RP) may potentially cure patients who have isolated local prostate cancer recurrence after radiotherapy (RT). We report the long-term cancer control associated with salvage RP in a consecutive cohort of patients and identify the variables associated with disease progression and cancer survival. METHODS AND MATERIALS: A total of 100 consecutive patients underwent salvage RP with curative intent for biopsy-confirmed, locally recurrent, prostate cancer after RT. Disease progression after salvage RP was defined as a prostate-specific antigen (PSA) level of > or =0.2 ng/mL or by initiation of androgen deprivation therapy. Cancer-specific mortality was defined as active clinical disease progression despite castration. Cox regression analysis was used to evaluate these endpoints. The median follow-up from RT was 10 years (range, 3-27 years) and from salvage RP was 5 years (range, 1-20 years). RESULTS: Overall, the 5-year progression-free probability was 55% (95% confidence interval, 46-64%), and the median progression-free interval was 6.4 years. The preoperative PSA level was the only significant pretreatment predictor of disease progression in the multivariate analysis (p = 0.01). The 5-year progression-free probability for patients with a preoperative PSA level of <4, 4-10, and >10 ng/mL was 86%, 55%, and 37%, respectively. The 10-year and 15-year cancer-specific mortality after salvage RP was 27% and 40%, respectively. The median time from disease progression to cancer-specific death was 10.3 years (95% confidence interval, 7.6-12.9). After multivariate analysis, the preoperative serum PSA level and seminal vesicle or lymph node status correlated independently with disease progression. CONCLUSIONS: Greater preoperative PSA levels are associated with disease progression and cancer-specific death. Long-term control of locally recurrent prostate cancer after definitive RT is possible when salvage RP is performed early in the course of recurrent disease.     

The prognostic impact of cytokeratin-positive cells in bone marrow of patients with localized prostate cancer

Our study evaluates the prognostic significance of the cytokeratin-positive mononuclear cells (CK+ cells) in the bone marrow (BM) and peripheral blood (PB) as detected by immunocytochemistry in patients with locoregionally confined prostate cancer. BM and PB samples were obtained from 66 newly diagnosed patients with T1-4pN0M0 prostate cancer. All samples were analyzed by standardized immunocytochemical methods (anticytokeratin mononuclear antibody; AE1/AE3) applying a negative immunomagnetic cell enrichment technique. A second sampling was obtained in 60 of the 66 patients >or=2 years after definitive radiotherapy. The median follow-up after high-dose radiotherapy of the patients was 65 months. For the analysis of the postradiotherapy clinical progression-free survival (PFS) treatment, failure was defined as pelvic tumor growth or development of distant metastases. At diagnosis CK+ cells were found in BM in 14 of 66 (21%) prostate cancer patients. This was not associated with an increased risk of progression. On the other hand, the presence of CK+ cells in 12 of 60 (20%) patients at the second BM aspiration was significantly related to a shorterPFS (p = 0.02). In the multivariate analysis, the presence of CK+ cells in the posttreatment BM did not remain as an independent variable of PFS assessment if posttreatment PSA was entered into the analysis. CK+ cells in PB were found in 12% of the patients. After therapy, none of the patients had detectable CK+ cells in PB. The presence of CK+ cells in the posttreatment but not in the pretreatment BM was associated with decreased PFS in patients irradiated for pelvis-confined nonmetastatic prostate cancer. Although this association was not retained in multivariate analysis, our observations indicate that the presence of CK+ cells after local therapy define a group of patients that have a high risk of developing distant metastases.     

Combination of somatostatin analog, dexamethasone, and standard androgen ablation therapy in stage D3 prostate cancer patients with bone metastases.

PURPOSE: Androgen ablation-refractory prostate cancer patients (stage D3) develop painful bone metastases and limited responsiveness to conventional therapies, hence the lack of universally accepted "gold standard" treatment for this poor prognosis clinical setting. We tested the safety and efficacy in stage D3 patients of the combination hormonal therapy, which combines administration of somatostatin analog and dexamethasone with standard androgen ablation monotherapy (luteinizing-hormone releasing-hormone analog or orchiectomy). EXPERIMENTAL DESIGN: Thirty eight patients with stage D3 prostate cancer (mean age 71.8 +/- 5.9 years) continued receiving androgen ablation therapy in combination with oral dexamethasone (4 mg daily for the 1st month of treatment, tapered down to 1 mg daily by the 4th month, with 1 mg daily maintenance dose thereafter) and somatostatin analog (20 mg octreotide i.m. injections every 28 days). RESULTS: Twenty-three of 38 patients (60.5%) receiving this combination regimen had partial responses [PR, >/=50% prostate-specific antigen (PSA) decline], 9 (21.1%) had stable disease, and 7 (18.4%) had progressive disease. In 47.7% (18 of 38) of patients, their serum PSA levels decreased with treatment but did not return to their respective baselines until the end of follow-up (or death from non-prostate cancer-related causes). The median time-to-return to baseline PSA was 12 months (95% CI, 7-17 months), median progression-free survival was 7 months (95% CI, 4.5-9.5 months), median overall survival was 14 months (95% CI, 10.7-17.4 months), and median prostate cancer-specific overall survival (defined as time from onset of combination therapy until prostate cancer-related death) was 16.0 months (95% CI, 11.9-20.1 months). All patients reported significant and durable improvement of bone pain and performance status (for a median duration of 14 months; 95% CI, 9-19 months), without major treatment-related side effects. We observed a statistically significant (P < 0.01) reduction in serum insulin-like growth factor-1 levels at response to the combination therapy. T levels remained suppressed within castration levels at baseline and throughout therapy, including relapse. CONCLUSION: The combination therapy of dexamethasone plus somatostatin analog and standard androgen ablation manipulation produces objective clinical responses and symptomatic improvement in androgen ablation-refractory refractory prostate cancer patients.     

前列腺特异膜抗原对前列腺疾病的临床诊断意义

目的评价血清中前列腺特异膜抗原（PSMA）浓度对前列腺疾病的辅助诊断意义。方法采用Western印迹分析检测患者血清中PSMA的浓度,前列腺特异抗原（PSA）检测采用通用的免疫化学发光法检测。分析二者在不同分组中的浓度差异及相关性。结果前列腺癌患者的血清中PSMA浓度显著高于正常人群,良性前列腺增生和前列腺炎的患者则低于正常人群,而PSA浓度无论是前列腺癌还是前列腺良性病变均高于正常人。结论前列腺特异膜抗原浓度可以作为区分前列腺癌和良性前列腺增生的辅助诊断标志物。     

Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) for determining prognosis in advanced stage hormone relapsing prostate cancer

Prostate cancer frequently progresses despite early diagnosis and appropriate treatment with radical prostatectomy and/or radiotherapy. The clinical utility of SELDI-TOF MS to identify serum biomarker patterns associated with prostate cancer progression was examined by analysis of the serum proteome of advanced prostate cancer patients receiving standard androgen deprivation therapy. Serum from advanced-stage patients receiving androgen deprivation therapy was profiled by SELDI-TOF MS. Group 1 patients (n=15) had stable prostate specific antigen (PSA) responses to treatment; Group 2 (n=16) had rising PSA levels. Spectra were subjected to peak identification following total ion current (TIC) normalization. Peak intensities with m/z between 2,000 and 20,000 were tested for group differences via Kruskal-Wallis tests, and assessed individually for PSA-independent associations with overall survival via covariate-adjusted Cox regressions. TIC normalization yielded 53 useable spectra; 119 peaks with m/z between 2,000 and 20,000 were identified. Seven peaks showed statistically significant (p<0.05) differences between PSA groups, and several other peaks showed significant associations with overall survival independent of PSA status. In summary, SELDI-TOF MS captured a specific biomarker profile associated with biochemical relapse and provided additional prognostic information regarding long-term survival, independent of clinical PSA status.     

前列腺特异性抗原人类激肽释放酶2和前列腺特异的膜抗原在前列腺癌患者外周血表达的临床意义

目的　探讨检测前列腺癌微转移的灵敏和特异性指标。方法　从 5 1例前列腺癌、33例前列腺增生 (BPH)患者及 32名正常人的外周血中分离单个核细胞 ,用巢式RT PCR方法检测其中前列腺上皮细胞前列腺特异性抗原 (PSA)、人类激肽释放酶 2 (hK2 )和前列腺特异的膜抗原 (PSMA)的表达。结果　PSA、hK2和PSMA在前列腺癌患者外周血中检出的阳性率分别为 5 2 .9%、4 3.1%和6 4 .7% ;正常人和BPH患者假阳性率分别为 6 .2 %、7.7%和 4 .6 % ,3项指标差异均有显著性 (P <0 .0 1)。各临床分期 (局限癌、侵袭性癌和转移癌 )间 ,PSA和hK2的阳性检出率差异无显著性 ;PSMA在各期前列腺癌中阳性检出率均较PSA和hK2高 ,且随临床分期进展 ,其阳性检出率亦增加 (P <0 .0 5 )。结论PSMA对前列腺癌诊断、治疗方案的选择及预后评估较PSA和hK2有更大的价值     

Chlorambucil and lomustine (CL56) in absolute hormone refractory prostate cancer: re-induction of endocrine sensitivity an unexpected finding

The management of androgen independent prostate cancer is increasingly disputed. Diethylstilbestrol and steroids have useful second-line activity in its management. The value of chemotherapy still remains contentious. This paper reports a phase 2 study of two orally active chemotherapy drugs in patients who are absolutely hormone refractory having failed primary androgen blockade and combined oestrogens and corticosteroids. In total, 37 patients who were biochemically castrate with absolute hormone refractory prostate cancer and performance status of 0-3 were enrolled. Therapy consisted of chlorambucil 1 mg kg(-1) given as 6 mg a day until the total dose was reached and lomustine 2 mg kg(-1) given every 56 days (CL56). During this time all hormone therapy was stopped. One patient normalised his PSA with a further two having a greater than 50% decline leading to an objective response rate of 10%. The median time to progression was 3.6 months with an overall survival of 7.1 months. The median survival of this group of patients from first becoming androgen independent was 23.5 months. Eight of 17 (47%) patients who were subsequently re-challenged with hormonal therapy following failure of chemotherapy had a further PSA reduction, three (17%) of which were >50%. The median progression-free interval for the eight patients was 4 months. In conclusion, CL56 has a low objective response rate in the management of absolute hormone refractory prostate cancer. Toxicity was mild. Re-induction of hormone sensitivity following failure of chemotherapy was an unexpected finding that requires further study.     

Combined androgen blockade with bicalutamide for advanced prostate cancer

BACKGROUND:

A previously reported, double‐blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone‐releasing hormone agonist (LHRH‐A) plus bicalutamide 80 mg versus LHRH‐A plus bicalutamide‐matching placebo (LHRH‐A monotherapy). The analysis at a median follow‐up of 2.4 years indicated that CAB significantly (P < .001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long‐term follow‐up (median, 5.2 years) were analyzed.

METHODS:

All deaths irrespective of cause and all prostate cancer‐specific deaths were recorded. The data were analyzed using Cox regression analysis and the log‐rank test.

RESULTS:

At a median follow‐up of 5.2 years, a significant overall survival advantage was observed in favor of CAB over LHRH‐A monotherapy (Cox regression analysis: hazard ratio, 0.78; 95% confidence interval, 0.60‐0.99; P = .0498; log‐rank test: P = .0425). The difference in cause‐specific survival between the 2 groups was not significant. The achievement of a prostate‐specific antigen (PSA) nadir concentration ≤1 ng/mL was a prognostic factor for improved survival. More patients attained PSA nadir concentrations ≤1 ng/mL with CAB compared with patients who received LHRH‐A monotherapy (81.4% vs 33.7%; P < .001).

CONCLUSIONS:

CAB with bicalutamide 80 mg offered a significant overall survival benefit compared with LHRH‐A monotherapy without reducing tolerability in patients with locally advanced or metastatic prostate cancer. Cancer 2009. © 2009 American Cancer Society.     

The association between measures of progression and survival in castrate-metastatic prostate cancer.

PURPOSE: To explore the association between progression-free survival and overall survival time in patients with castration-resistant prostate cancer treated with microtubule-targeted therapies. EXPERIMENTAL DESIGN: We retrospectively studied patients treated in three trials evaluating a taxane or an epothilone for progressive castration-resistant prostate cancer. Study subjects were 98 patients with bone metastases; 63 of them also had soft tissue lesions. All scans were reviewed independently. Associations of radiographic progression-free survival and prostate-specific antigen (PSA) progression-free survival with survival time were measured using Kendall's tau, adjusted for right censoring. A smoothing procedure was applied to estimate Kendall's tau within each neighborhood of the follow-up process. RESULTS: The overall associations between progression-free survival time and overall survival time were moderate: 0.4 for radiographic progression-free survival and 0.33 for PSA progression-free survival. The association between radiographic progression-free survival and overall survival was weakest early in the follow-up process, whereas the PSA association was weakest when the progression-free survival-related event (PSA progression, death, or censoring) occurred after 6 months from the start of treatment. CONCLUSIONS: Current measures of progression-free survival time for men with castration-resistant prostate cancer are not strongly concordant with survival time. Factors that attenuate the association include interval censoring and the discontinuation of therapy early in the follow-up due to imaging changes that may not reflect true failure of the treatment. For radiographic progression-free survival, the association may be increased by requiring confirmation of progression with a second scan, as is routinely done when assessing response.     

Impact of supplemental external beam radiotherapy and/or androgen deprivation therapy on biochemical outcome after permanent prostate brachytherapy

PURPOSE: To evaluate the impact of supplemental external beam radiotherapy (EBRT) and/or androgen deprivation therapy (ADT) on 8-year biochemical outcome after permanent prostate brachytherapy. METHODS AND MATERIALS: Between April 1995 and January 2001, 668 consecutive patients underwent brachytherapy using either (103)Pd or (125)I for clinical Stage T1b-T3aNxM0 (2002 American Joint Committee on Cancer) adenocarcinoma of the prostate gland. No patient underwent seminal vesicle biopsy or pathologic lymph node staging. The median follow-up was 58.6 months. Biochemical progression-free survival was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. The clinical, treatment, and dosimetric parameters evaluated for biochemical progression-free survival included supplemental EBRT, ADT, patient age, clinical stage, Gleason score, preimplant prostate specific antigen (PSA), risk group, percentage of positive biopsies, isotope used, prostate volume, planning volume, percentage of target volume receiving 100%, 150%, and 200% of prescribed dose, minimal percentage of dose covering 90% of target volume, tobacco status, hypertension, and diabetes. RESULTS: For the entire group, the actuarial 8-year biochemical progression-free survival rate was 98.2%, 98.4%, and 88.2% for low-, intermediate-, and high-risk patients, respectively, with a median PSA level of <0.1 ng/mL for all risk groups and ADT and EBRT subgroups. At last follow-up, only 5 patients (0.8%) had died of metastatic prostate cancer. In multivariate analysis, Gleason score, percentage of positive biopsies, and ADT predicted for biochemical outcome in high-risk patients. In low- and intermediate-risk patients, none of the evaluated variables predicted for biochemical outcome. For the entire population, pretreatment PSA level, Gleason score, ADT, and clinical stage predicted for 8-year biochemical progression-free survival, with the percentage of positive biopsies approaching statistical significance. CONCLUSION: Prostate brachytherapy results in a high probability of 8-year biochemical progression-free survival for low-, intermediate-, and high-risk patients. Although the role of supplemental EBRT could not be adequately evaluated in high-risk patients, it did not improve biochemical outcome in low- and intermediate-risk patients. However, ADT resulted in a statistically significant improvement in progression-free survival for high-risk patients.     

Chlormadinone Acetate Withdrawal Syndrome under Combined Androgen Blockade for Advanced Prostate Cancer

Between July 1991 and December 1994 at Tsukuba Gakuen Hospital,we treated 19 consecutive men with advanced adenocarcinoma ofthe prostate (five at stage C, four at stage D1 and 10 at stageD2). Of these, 14 patients underwent castration (two patients)or received LH-RH analogue (12 patients) plus chlormodinoneacetate for combined androgen blockade. We report three representativecases of sequential prostate specific antigen (PSA) elevationfollowing initial response to this combined androgen blockade.Discontinuation of chlormadinone acetate resulted in declineof the serum PSA level. This suggests that trial chlormadinoneacetate withdrawal in patients showing increasing levels ofPSA during combined androgen blockade should be considered beforeinitiation of alternative treatment.     

Clinical outcome of oral uracil/tegafur (UFT) therapy for patients with hormone refractory prostate cancer

There is no standard therapeutic strategy for advanced hormone refractory prostate cancer after the initial hormonal therapy fails. The objective of this study was to retrospectively evaluate the clinical outcome of the oral anticancer agent, uracil/tegafur (UFT) for patients with hormone refractory prostate cancer. This study included 68 patients with hormone refractory prostate cancer treated by oral administration of UFT (300-600 mg/day). All patients had previously received maximum androgen blockade (MAB) which failed. In this series, response was defined as more than 50% decrease from the baseline prostate specific antigen (PSA) value at the start of second line therapy. Upon initiating administration of UFT, a reduction in PSA value was observed in 41 of the 68 patients (60.3%), among whom 13 (19.1%) were regarded as responders; however, PSA value continued to increase in the remaining 27 (39.7%). Median duration of PSA response was 7 months (range 1-22 months). During the observation period, there were no severe side effects due to UFT administration, but 7 patients transiently presented appetite loss. Patients without bone metastasis at the initial diagnosis or whose serum PSA value at the start of UFT therapy was less than 2.0 ng/ml showed a significantly higher incidence of PSA response to UFT; however, other factors examined had no significant impact on PSA response to UFT. Furthermore, cause-specific survival in responders to UFT therapy was significantly better than that in non-responders. These findings suggest that administration of UFT after the failure of initial MAB therapy can achieve a comparatively favorable PSA response without severe side effects; therefore, it may be worthy to consider administering UFT to patients with hormone refractory prostate cancer.     

前列腺特异性膜抗原和前列腺特异性抗原表达强度与前列腺癌Gleason评分之间的相关性研究

目的研究前列腺特异性膜抗原(PSMA)和前列腺特异性抗原(PSA)的表达强度与前列腺癌Gleason评分之间的相关性。方法制备抗PSMA膜外段表位的单克隆抗体,应用免疫组织化学方法检测前列腺癌中PSMA的表达,统计分析其与Gleason评分之间的相关性,并和PSA与Gleason评分之间的相关性进行对比。结果制备出8株分泌抗PSMA膜外段表位的单抗的杂交瘤细胞株。免疫组化结果表明,PSMA的表达强度与前列腺癌的Gleason评分之间存在相关性。在分化差的前列腺癌中,PSMA水平高于分化中等和分化良好的前列腺癌(P<0.01),而PSA在前列腺癌中的表达无明显差异(P>0.05)。结论PSMA表达水平在分化差的前列腺癌中明显升高,与Gleason评分存在相关性,可以作为前列腺癌的Gleason分级的标记物,提示PSMA可以作为对激素疗法效果不敏感的低分化前列腺癌抗体介导的免疫治疗靶点。     

Clinical and socio‐demographic profile of an Australian multi‐institutional prostate cancer cohort

Aims: To describe the clinical and socio‐demographic data from a South Australian prostate cancer cohort (PCCOD). Methods: Clinical data for 2329 prostate cancer patients treated at three South Australian teaching hospitals between 1998 and 2007 were analyzed by place of residence, time of diagnosis and socioeconomic status (SES). χ² tests were used to investigate differences in stage, grade and prostate‐specific antigen (PSA) at diagnosis, among subgroups and over time. Logistic regression was used to examine predictors of treatment modalities. Five‐year survival was assessed using Kaplan–Meier methods. Results: The distributions of age, SES and place of residence of PCCOD patients closely reflected those of the state‐based prostate cancer population, with rural patients slightly underrepresented. Lower SES or rural residence was not associated with higher stage, grade, PSA level or disease‐specific survival. Treatment modalities varied with SES (for radical prostatectomy), rural residence (radical prostatectomy, radiotherapy and androgen ablation), age and clinical characteristics. There was a trend over time towards a younger age at diagnosis and more favorable clinical profiles, consistent with earlier diagnosis. However, the current risk profile for this cohort is similar to that reported approximately a decade earlier in a US series. Conclusion: PCCOD patients have a broadly similar socio‐demographic profile to prostate cancer patients statewide. Socioeconomic status is not associated with clinical characteristics at diagnosis, but does predict treatment type. The clinical characteristics of the cohort are consistent with a much later stage presentation than reported in current US case series.     

Diagnostic Efficacy of PSMA and PSCA mRNAs Combined to PSA in Prostate Cancer Patients

Background: Serum Prostate-specific antigen (PSA) has been used for screening and diagnosis of prostate cancer (PCa) but it is burdened by its low accuracy, creating a need for reliable diagnostic markers. Despite prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA) being widely expressed in the tissue of PCa, no definite conclusion regarding their use as clinical biomarkers due to their lacking organ specificity. Therefore, this study aimed to evaluate the peripheral blood levels of PSMA and PSCA mRNAs and examine their diagnostic significance as non-invasive integrated markers.Materials and Methods: 125 subjects were enrolled in this study. They were divided into 25 healthy controls, 25 BPH patients, and 75 PCa patients. The expression levels of PSMA and PSCA were determined using quantitative RT- PCR, in addition to measuring serum PSA.Results: Levels of PSMA and PSCA were over-expressed in PCa patients compared to controls and BPH patients and were found to be associated with increased susceptibility to PCa. Moreover, the diagnostic values of PSMA and PSCA to distinguish PCa patients from BPH patients and controls were inferior to that of PSA. However, the combination of PSMA and PSCA with PSA enhanced the efficacy of the latter.Conclusion: This study suggests that these genes were associated with malignant susceptibility. Concerning the duality of PSMA-PSA or PSCA-PSA, this implies the significance of their investigation together in peripheral blood of prostate patients.     

Natural history of rising serum prostate-specific antigen in men with castrate nonmetastatic prostate cancer.

PURPOSE: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy. PATIENTS AND METHODS: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were baseline PSA, Gleason sum, history of bilateral orchiectomies, regional lymph node metastases at diagnosis, prior prostatectomy, time from androgen deprivation therapy to random assignment, time from diagnosis to random assignment, and PSA velocity. RESULTS: At 2 years, 33% of patients had developed bone metastases. Median bone metastasis-free survival was 30 months. Median time to first bone metastases and overall survival were not reached. Baseline PSA level greater than 10 ng/mL (relative risk, 3.18; 95% CI, 1.74 to 5.80; P < .001) and PSA velocity (4.34 for each 0.01 increase in PSA velocity; 95% CI, 2.30 to 8.21; P < .001) independently predicted shorter time to first bone metastasis. Baseline PSA and PSA velocity also independently predicted overall survival and metastasis-free survival. Other covariates did not consistently predict clinical outcomes. CONCLUSION: Men with nonmetastatic prostate cancer and rising PSA despite androgen deprivation therapy have a relatively indolent natural history. Baseline PSA and PSA velocity independently predict time to first bone metastasis and survival.     

Clinical and socio-demographic profile of an Australian multi-institutional prostate cancer cohort

Aims:   To describe the clinical and socio-demographic data from a South Australian prostate cancer cohort (PCCOD).
Methods:   Clinical data for 2329 prostate cancer patients treated at three South Australian teaching hospitals between 1998 and 2007 were analyzed by place of residence, time of diagnosis and socioeconomic status (SES). χ² tests were used to investigate differences in stage, grade and prostate-specific antigen (PSA) at diagnosis, among subgroups and over time. Logistic regression was used to examine predictors of treatment modalities. Five-year survival was assessed using Kaplan–Meier methods.
Results:   The distributions of age, SES and place of residence of PCCOD patients closely reflected those of the state-based prostate cancer population, with rural patients slightly underrepresented. Lower SES or rural residence was not associated with higher stage, grade, PSA level or disease-specific survival. Treatment modalities varied with SES (for radical prostatectomy), rural residence (radical prostatectomy, radiotherapy and androgen ablation), age and clinical characteristics. There was a trend over time towards a younger age at diagnosis and more favorable clinical profiles, consistent with earlier diagnosis. However, the current risk profile for this cohort is similar to that reported approximately a decade earlier in a US series.
Conclusion:   PCCOD patients have a broadly similar socio-demographic profile to prostate cancer patients statewide. Socioeconomic status is not associated with clinical characteristics at diagnosis, but does predict treatment type. The clinical characteristics of the cohort are consistent with a much later stage presentation than reported in current US case series.     

Correlation of primary tumor prostate-specific membrane antigen expression with disease recurrence in prostate cancer.

PURPOSE: The restricted expression of the surface glycoprotein prostrate-specific membrane antigen (PSMA) to normal prostate tissue, primary and metastatic prostate cancer (PCa), and the neovasculature of various nonprostatic epithelial malignancies has enabled targeting strategies for PCa treatment using anti-PSMA antibodies. EXPERIMENTAL DESIGN: Using prostatectomy specimens, immunohistochemical staining for PSMA (7E11 antibody) was performed on formalin-fixed paraffin-embedded sections of 136 cases of PCa. Cytoplasmic immunoreactivity was scored for intensity and distribution, and results were correlated with tumor grade, pathological stage, DNA ploidy status (Feulgen spectroscopy), and disease recurrence. PSMA mRNA expression in selected primary tumors and metastatic lesions was also detected using in situ hybridization and autoradiography. RESULTS: Generally, PCa cells expressed relatively increased levels of PSMA as compared with benign elements. Among the PCa cases, increased (high) PSMA expression correlated with tumor grade (P = 0.030), pathological stage (P = 0.029), aneuploidy (P = 0.010), and biochemical recurrence (P = 0.001). The mean serum prostate-specific antigen level of 18.28 ng/ml at the time of diagnosis for the PSMA-overexpressing tumors was significantly greater than the mean serum prostate-specific antigen of 9.10 ng/ml for the non-PMSA-overexpressing group (P = 0.006). On multivariate analysis, pathological stage (P = 0.018) and PSMA expression (P = 0.002) were independent predictors of biochemical recurrence. PSMA protein overexpression in high-grade primary PCa tumors and metastatic lesions also correlated with increased PSMA mRNA expression levels using in situ hybridization and autoradiography. CONCLUSIONS: This study demonstrates for the first time that overexpression of PSMA in primary PCa correlates with other adverse traditional prognostic factors and independently predicts disease outcome.