Usefulness of ultrasensitive prostate-specific antigen assay for early detection of biochemical failure after radical prostatectomy

BACKGROUND: In order to assess whether the prostate-specific antigen (PSA) nadir obtained with an ultrasensitive PSA assay can be used as a prognostic indicator for patients undergoing radical prostatectomy, we investigated it retrospectively. METHODS: Between October 1997 and July 2003, 46 patients underwent radical prostatectomy for prostate cancer at our institution. None of them received preoperative treatment. Levels of PSA were measured with an ultrasensitive PSA assay every 1-3 months after prostatectomy. Biochemical recurrence was defined as a PSA level of 0.2 ng/mL or higher. RESULTS: There was a significant difference in PSA nadir between the biochemical recurrence group and the no recurrence group (P < 0.001). The receiver operating characteristics (ROC) curve gave an optimal cut-off value for PSA nadir of 0.01 ng/mL, demonstrating a significant difference in biochemical recurrence after radical prostatectomy. No patient with a PSA nadir level <0.01 ng/mL showed biochemical failure, while 15 out of 22 patients with PSA nadir levels >or=0.01 ng/mL showed biochemical failure. CONCLUSION: The PSA nadir level obtained using an ultrasensitive PSA assay is an excellent predictor of biochemical recurrence after radical prostatectomy. Early detection of recurrence offers the possibility of early salvage therapy.     

Clinicopathological features of patients with biochemical recurrence after radical prostatectomy without progressive rise in serum prostate-specific antigen

INTRODUCTION: The objective of this study was to characterize clinicopathological features of patients with biochemical recurrence after radical prostatectomy who did not exhibit a progressive rise in serum prostate-specific antigen (PSA) during the follow-up period. MATERIALS AND METHODS: We analyzed data from 162 consecutive patients who underwent radical prostatectomy for clinically organ-confined prostate cancer without neoadjuvant hormonal therapy and were followed postoperatively for at least 1 year. The serum PSA value was measured using an ultrasensitive PSA assay system (Roche Diagnostics, Mannheim, Germany), and biochemical recurrence was defined as a serum PSA of >or=0.1 ng/ml. RESULTS: A total of 32 patients (19.8%) were diagnosed as having biochemical recurrence. Among these patients, we identified 10 (31.3%) with a serum PSA>0.1 ng/ml who had not shown PSA or clinical progression during a median follow-up of 34 months after radical prostatectomy. In these 10 patients, the median time to biochemical recurrence was 17 months, the median PSA velocity after biochemical recurrence was 0.034 ng/ml/year, and there was no patient whose serum PSA value became >0.4 ng/ml. There were no clinicopathological parameters except for PSA velocity that were significantly associated with the features of these 10 patients. CONCLUSION: Because of the presence of a subset of patients with biochemical recurrence after radical prostatectomy who will not show a progressive increase in serum PSA value, the indication for adjuvant therapy for such patients should be cautiously determined considering several factors, such as PSA kinetics.     

Prostate specific antigen nadir determined using ultra-sensitive prostate specific antigen as a predictor of biochemical progression after radical prostatectomy in Japanese males

OBJECTIVES: We examined whether the prostate specific antigen (PSA) nadir is a good predictor of biochemical failure after radical prostatectomy. METHODS: We retrospectively reviewed clinico-pathological data in 257 patients who underwent radical prostatectomy. Twenty-nine patients of whom PSA nadir did not reach 0.1 ng/mL and three patients in whom second line therapy was started before biochemical failure were excluded, and 225 patients were subject to this study. We evaluated the changes in PSA value at very low (from less than 0.01-0.10 ng/mL) levels using an ultra-sensitive PSA assay after radical prostatectomy. Biochemical failure was defined as three consecutive elevations of PSA to above 0.1 ng/mL. RESULTS: Biochemical failure-free survival was attained by 89.9% of patients at 1 year, 83.0% at 2 years, and 81.0% at 5 years. PSA nadir more than 0.01 ng/mL was strongly associated with biochemical failure after radical prostatectomy (P < 0.0001). Mean time to reach PSA nadir was 3.1 months. Preoperative PSA > 20 ng/mL (P = 0.0013), clinical T stage = T2 (P = 0.0462), Gleason score 8-10 (P = 0.0243) were also independent predictors of biochemical progression. CONCLUSIONS: Prostate specific antigen nadir determined by ultra-sensitive PSA assay is an important parameter that is objective, reliable, and easily measured, and useful for predicting the subgroups of patients both most likely and unlikely to exhibit biochemical progression.     

Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy

PURPOSE: Ultrasensitive prostate specific antigen (PSA) assays allow a lower limit of detection (less than 0.01 ng/ml) than standard PSA assays. In this study we examined the ability of ultrasensitive PSA nadir to predict relapse after radical prostatectomy (RP). MATERIALS AND METHODS: A total of 906 men treated with RP were followed with PSA measurements at 3, 6 and 12 months, and yearly thereafter. Of the 906 men 545 (60%) with a PSA nadir of less than 0.01 ng/ml or at least 3 followup ultrasensitive PSA measurements underwent analysis and stratification by PSA nadir. Biochemical relapse was defined as 2 consecutive increasing post-nadir PSA measurements of 0.1 ng/ml or greater. The ability of ultrasensitive PSA nadir to predict relapse was assessed by univariate and multivariate analysis. RESULTS: At a mean followup of 3.1 years 54 of 545 men (9.9%) experienced biochemical relapse with a mean time to relapse of 25.2 months. Relapse rates in men with a PSA nadir of less than 0.01 (423), 0.01 (75), 0.02 (19) and 0.04 or greater ng/ml (28) were 4%, 12%, 16% and 89%, respectively. Men with a nadir of less than 0.01 ng/ml had a significantly lower relapse rate than men with a nadir of 0.01 (p <0.01), 0.02 (p <0.025) or 0.04 or greater ng/ml (p <0.01). Multivariate logistic regression analysis showed that a nadir of 0.01 (p <0.05), 0.02 (p <0.05) and 0.04 or greater ng/ml (p <0.01) independently predicted an increased risk of biochemical relapse compared to a nadir of less than 0.01 ng/ml. CONCLUSIONS: Ultrasensitive PSA nadir accurately predicts the risk of early biochemical relapse following RP. Men who achieve a nadir of less than 0.01 ng/ml have a low likelihood of early relapse. Higher nadir points may identify candidates for early adjuvant or salvage therapies.     

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.     

Sensitive Prostate Specific Antigen Measurements Identify Men With Long Disease-Free Intervals and Differentiate Aggressive from Indolent Cancer Recurrences within 2 Years After Radical Prostatectomy

Purpose

Commonly available prostate specific antigen (PSA) assays have detection limits of greater than 0.05 ng./ml., limiting their ability to identify residual or recurrent prostate cancer after radical prostatectomy or to provide prognostic information within the first several years after surgery. We investigated the ability of a sensitive PSA assay to identify residual prostate cancer and men at risk for early recurrence after radical prostatectomy.

Materials and Methods

We measured PSA in 1,037 serum samples obtained serially from 127 men after radical prostatectomy using the IMMULITE' third generation PSA assay.'Diagnostic Products Corp., Los Angeles, California.

Results

The IMMULITE PSA assay has an analytical sensitivity of less than 0.002 ng./ml. and a clinically useful decision threshold of 0.01 ng./ml. With this assay our patients were classified into 3 groups: 1) 50 with a postoperative baseline PSA of less than 0.01 ng./ml. that did not change during an average of 36 months postoperatively, 2) 66 with increasing PSA that exceeded 0.01 ng./ml. in all cases by 30 months postoperatively (20 with clinical cancer recurrences) and 3) 11 with slowly increasing PSA of greater than 0.01 but less than 0.02 ng./ml. at an average of 36 months postoperatively.

Conclusions

The IMMULITE PSA assay provides clinically useful information not previously available from PSA assays with conventional sensitivity, which is highly predictive of cancer activity in patients within 2 years after radical prostatectomy.     

Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy

PURPOSE: We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS: Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant. RESULTS: Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard assay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapses were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurrence. CONCLUSIONS: Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.     

Ultrasensitive Assay of Prostate-Specific Antigen for Early Detection of Residual Cancer after Radical Prostatectomy

Objectives : Perhaps the greatest value of PSA determination in the treatment of prostate cancer is in determining persistent disease after a radical prostatectomy. We investigated the ability of an ultrasensitive PSA assay to detect residual prostate cancer in men at risk for recurrence after a radical prostatectomy.
Methods : Using the Immulite third-generation PSA assay (detection limit, less than 0.003 ng/mL), and the standard IMx PSA assay, we determined PSA levels in 205 serum samples serially obtained from 34 men after a radical prostatectomy. The average days from surgery to serum sampling was 430 (range, 63 to 1 296). Patients were classified as having nonaggressive or aggressive cancers, based on clinicopathologic findings. A biochemical relapse was arbitrarily defined.
Results : All 1 7 patients with nonaggressive cancers had PSA values of less than 0.02 ng/mL throughout the sampling period. Two of these patients (12%) had 2 or more consecutive PSA increases and were considered as a biochemical relapse. In contrast, 14 (82%) of 1 7 patients with aggressive cancers fit criteria of a biochemical relapse. All of the relapses were identified within 2 years after surgery. The IMx assay detected only 7 biochemical relapses during the same sampling period.
Conclusions : Using the Immulite PSA assay, relapse detection times may be shortened allowing for most serological recurrences to be detected within 2 years after a radical prostatectomy. Patients with aggressive cancers may require frequent postoperative PSA determinations with a highly sensitive PSA assay which would allow early intervention when treatments for relapse are effective.     

Serum prostate-specific antigen value adjusted for non-cancerous prostate tissue volume in patients undergoing radical prostatectomy: a new predictor of biochemical recurrence in localized or locally advanced prostate cancer

The aim of this study was to investigate the significance of serum prostate-specific antigen (PSA) value adjusted for total tumor volume (PSA/tumor volume) and serum PSA value adjusted for non-cancerous prostate tissue volume (NCPV) (PSA/NCPV) as a predictor of pathological findings and clinical outcome after radical prostatectomy. Clinical and pathological data of 407 patients (median age: 66.5 years; range: 41.8-85.7 years) were reviewed retrospectively. The median follow-up period was 18.1 months (range: 1.0-107.8 months). Biochemical recurrence was defined as detectable PSA levels (greater than 0.2 ng ml(-1)) and the time of biochemical recurrence was taken to be the first time PSA became detectable. In the multivariate model, PSA/NCPV was an independent predictor of extracapsular extension and positive surgical margin (P<0.05), but PSA/tumor volume was not. Kaplan-Meier curves revealed that PSA/NCPV correlated with biochemical recurrence-free survival (P<0.001; log-rank test) but PSA/tumor volume did not (P=0.275; log-rank test). PSA/NCPV was also a significant independent prognostic factor for biochemical recurrence-free survival on multivariate Cox proportional hazard analysis (P=0.004, relative risk=2.42). Our findings suggest that PSA/NCPV is associated independently with extracapsular extension and surgical margin status and may be an independent prognostic variable of PSA recurrence after radical prostatectomy.     

ERG蛋白表达与前列腺癌患者根治术后生化复发风险关系的研究

目的 探讨临床局限性前列腺癌行根治性切除术后,组织ERG蛋白表达情况与术后生化复发的相关性。方法 选取2012年3月至2016年2月在本院治疗的121例局限性前列腺癌并行根治性切除术的患者作为研究对象,通过住院病历及门诊随访资料收集患者确诊时年龄、血清前列腺特异性抗原（PSA）水平、格里森评分（GS）、病理分期及切缘状态等参数。结果 共有98例患者完成最终随访,ERG蛋白表达阳性率为35.7%（35/98）。Kaplan-meier生存分析提示,确诊时PSA水平（P=0.007）、GS（P=0.024）及ERG蛋白表达状态（P<0.0001）,与术后生化复发相关。Cox回归多因素分析显示,确诊时PSA水平（HR=2.134,P=0.001）、GS（HR=1.361,P=0.030）及ERG蛋白表达状态(HR=2.024,P=0.044)分别为前列腺癌根治性切除术后生化复发的独立危险因素。结论 ERG蛋白表达状态是前列腺根治性切除术后生化复发的独立危险因素,通过对其检测及分析,可以为患者制定个体化的随访及临床治疗方案提供参考依据。     

Impact of preoperative serum PSA level from 0 to 10 ng/ml on pathological findings and disease-free survival after radical prostatectomy

BACKGROUND: To determine the impact of various preoperative serum prostate specific antigen (PSA) levels in the range from 0.1 to 10 ng/ml on pathological stage and disease-free survival after radical prostatectomy. METHODS: We selected a cohort of 585 patients who underwent radical prostatectomy between 1991-1996 for clinically localized prostate cancer and presented with preoperative serum PSA levels from 0.1 to 10 ng/ml. RESULTS: Pathological organ-confined disease was present in 57.6% of patients. The rate of organ-confined disease decreased from an average of 85% for patients with a PSA value < 2 ng/ml, to 46.8% for patients with a PSA value > 7 ng/ml. We found statistically significant correlations between preoperative serum PSA level and overall pathological stage (P = 0.001), pathologically organ-confined disease (P = 0.001), margin positive rates (P = 0.001), extra prostatic extension (P = 0.001), and seminal vesicle invasion (P = 0.001). The overall disease-free survival rate was 87%, with a median follow up of 42.4 months. Disease free survival was significantly better for patients with PSA up to 4 ng/ml (P = 0.005). CONCLUSIONS: Our data suggests that PSA detection programs should strive to detect prostate cancer in men before the PSA level rises above 7 ng/ml. In addition, since patients with a PSA level < 4 ng/ml had better disease-free survival rates than those with a PSA level between 4.1-10 ng/ml, eliminating an arbitrary cutoff of 4 ng/ml, may lead to improved disease-free survival.     

The limited significance of a longer duration of neoadjuvant hormonal therapy prior to radical prostatectomy for high-risk prostate cancer in Japanese men

INTRODUCTION: The objective of this study was to evaluate the therapeutic significance of a longer duration of neoadjuvant hormonal therapy (NHT) followed by radical prostatectomy (RP) in Japanese men with high-risk prostate cancer. MATERIALS AND METHODS: This study included a total of 42 patients with high-risk prostate cancer who were treated with NHT for >or=8 months prior to RP. In this series high-risk prostate cancer was defined as clinical stage T2c or T3, pretreatment serum prostate-specific antigen (PSA) >20 ng/ml and/or a biopsy Gleason score of 8-10. Biochemical recurrence was defined as a serum PSA level of >or=0.2 ng/ml. The data of these patients were retrospectively reviewed to clarify the relationships between treatment outcomes and various clinicopathological parameters. RESULTS: The clinical stage was T2c in 13 patients and T3 in 29, the median value of pretreatment serum PSA was 43.3 ng/ml (range 9.7-322.2), and the biopsy Gleason score was 6 in 3 patients, 7 in 16 and >or=8 in 23. Following NHT (median 12 months, range 8-27), the median value of serum PSA decreased to 0.05 ng/ml (<0.01-18.3 ng/ml), and 15 patients (35.7%) were pathologically downstaged. During the median follow-up of 38 months (range 8-58), 11 patients (26.2%) developed biochemical recurrence, and the multivariate analysis identified pretreatment serum PSA, biopsy Gleason score and percentage of positive biopsy core as independent predictors of biochemical recurrence. The 3-year biochemical recurrence-free survival rate of the 42 patients was 68.3%, which was not significantly different from that of 34 patients who underwent RP for high-risk prostate cancer without NHT during the same period. CONCLUSION: A longer duration of NHT followed by RP for patients with high-risk prostate cancer resulted in a comparatively favorable outcome. However, despite the nonrandomized retrospective analysis, the present findings suggest no significant impact of long-term NHT on biochemical recurrence. Longer follow-up is needed to determine whether this therapeutic strategy is beneficial for high-risk prostate cancer patients.     

Use of percent free prostate-specific antigen as a predictor of the pathological features of clinically localized prostate cancer

PURPOSE: To evaluate the usefulness of percent free serum prostate-specific antigen (PSA) as a predictor of the pathological features of prostate cancer. MATERIALS AND METHODS: Total and free serum PSA were measured preoperatively in 220 consecutive patients with clinically localized prostate cancer who underwent radical prostatectomy. Organ-confined disease and favorable pathology were considered as the outcomes for this study. RESULTS: Percent free serum PSA was not able to predict these outcomes in the overall population. However, it could significantly predict favorable pathology in a subset of patients in whom digital rectal examination (DRE) was normal and total PSA ranged from 4.1 to 10 ng/ml. A 11% cutoff provided a significant distribution with an odds ratio of 2.8 (95% confidence interval 1.1-7.0), a positive predictive value of 63. 3% and a negative predictive value of 46.3%. CONCLUSIONS: According to these results, we suggest that percent free PSA may provide additional information for the staging of clinically localized prostate cancer. However, the reference population for its usefulness would be those patients with normal DRE and total PSA between 4.1 and 10 ng/ml.     

PSA in the new millennium: a powerful predictor of prostate cancer prognosis and radical prostatectomy outcomes--results from the SEARCH database

OBJECTIVES: As a result of prostate-specific antigen (PSA) screening, most men today with prostate cancer present with localized disease and serum PSA values < 10 ng/ml. Within this context, it is debated whether PSA remains an important prognostic variable in more recently treated patients. We examined the prognostic significance of preoperative PSA to predict pathologic stage and biochemical progression among men undergoing radical prostatectomy in the new millennium (2000-2006). METHODS: We performed a review of 925 men with prostate cancer treated by radical prostatectomy since 2000 within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We examined the association between preoperative PSA and risk of adverse pathologic features and biochemical progression using logistic regression and Cox proportional hazards analysis. RESULTS: After adjusting for multiple clinical preoperative characteristics, higher preoperative PSA values were associated with increased odds of extracapsular extension (p<0.001), positive surgical margins (p<0.001), and seminal vesicle invasion (p<0.001) and increased risk of biochemical progression (p=0.009). When the analyses were limited to the 690 men with a preoperative PSA<10 ng/ml and after adjusting for multiple clinical characteristics, higher preoperative PSA values remained associated with increased risk of biochemical progression (hazard ratio [HR] 1.16, 95% confidence interval [CI] 1.06-1.28, p=0.002). Even among the 448 men with a PSA<10 ng/ml and clinical stage T1c disease, preoperative PSA was associated with increased risk of biochemical progression (HR 1.14, 95%CI 1.00-1.31, p=0.047). CONCLUSIONS: PSA remains an important prognostic marker among men diagnosed with prostate cancer in the new millennium treated with radical prostatectomy and remains an important predictor of outcome even among men with preoperative PSA level < 10 ng/ml.     

Biochemical (prostate specific antigen) recurrence probability following radical prostatectomy for clinically localized prostate cancer

PURPOSE: We retrospectively reviewed the clinical followup for a large series of men with clinically localized prostate cancer who underwent radical retropubic prostatectomy to identify clinical and/or pathological indicators of biochemical (prostate specific antigen [PSA]) recurrence. We then used those indicators to develop multivariate models for determination of recurrence probability following radical retropubic prostatectomy. MATERIALS AND METHODS: From 1982 to 1999, 2,091 consecutive men underwent radical retropubic prostatectomy and pelvic lymphadenectomy for clinically localized adenocarcinoma of the prostate (clinical stage T1c or T2 disease with Gleason score 5 or greater). Actuarial analysis was performed comparing freedom from biochemical recurrence after radical retropubic prostatectomy (PSA 0.2 ng./ml. or greater.) using the Kaplan-Meier method. Event time distributions for the time to recurrence were compared using the log rank statistic or the Cox proportional hazards regression model. The first model was developed using preoperative variables only and the second model using all available variables. Observed and predicted recurrence-free survival curves for different models were compared to select a model for calculation of predicted recurrence-free probabilities and confidence intervals. RESULTS: With a median followup of 5.9 years (range 1 to 17) 360 men (17%) had biochemical recurrence. Overall actuarial 5, 10 and 15-year biochemical recurrence-free survival rates were 84%, 72% and 61%, respectively. The relative risk of biochemical recurrence following surgery decreased with time, even after adjusted for other perioperative parameters. Variables identified for the preoperative model were biopsy Gleason score, clinical TNM stage and PSA. Variables identified for the postoperative model were prostatectomy Gleason score, PSA and pathological organ confinement status. Nomograms were generated and corrected for the decreasing relative risk of biochemical recurrence over time. CONCLUSIONS: Using 3 preoperative or postoperative parameters, these nomograms can easily be used to determine the 3, 5, 7 and 10-year biochemical recurrence-free survival probabilities among men who undergo radical retropubic prostatectomy for clinically localized prostate cancer in the modern era.     

Intermittent androgen deprivation therapy may prolong the duration of androgen dependence of well-differentiated prostate cancer

We previously reported the results of a pilot study of intermittent androgen deprivation (IAD) therapy in which surveillance was performed when PSA level fell below 0.3 ng/ml and androgen deprivation was resumed when PSA level exceeded 2.0 ng/ml. In the present study, we compared the duration of androgen dependence in patients treated with IAD with that in patients with continuous androgen deprivation (CAD) therapy. Forty-six patients with clinically localized or metastatic prostate cancer, or biochemical recurrence after radical prostatectomy were treated with IAD from 1995 to 2003. Patients in or after the second cycle of IAD (30 patients) were evaluated for duration of androgen dependence. Patients whose serum PSA nadir became <0.3 ng/ml (33 patients) represented a control group of CAD. The overall 5-year biochemical progression-free rate was 58% and 89% in the IAD and CAD groups, respectively; there was no significant difference between the two groups (p=0.5). Subgroup analysis showed that, irrespective of metastasis, the 5-year biochemical progression-free survival rate in the IAD group was not significantly different from that in the CAD group. However, IAD offered significantly better results for well-differentiated prostate cancer, whereas CAD offered significantly better results for moderately or poorly differentiated prostate cancer. The results obtained from this retrospective and nonrandomized study suggested that IAD may be a feasible treatment for well-differentiated prostate cancer.     

Variable definitions influence the reporting of biochemical failure rates

The purpose of this study was to assess how the reporting of biochemical failure (BF) rates would be affected by the application of three different definitions. Three hundred and fifteen men with localized prostate cancer underwent I-125 brachytherapy (n=109), conformal three-dimensional radiation therapy (n=99), or radical prostatectomy (n=107). No patient received adjuvant or neoadjuvant hormone therapy in this study. BF rates at 12, 24 and 36 months were assessed using three definitions: (1) prostate-specific antigen (PSA) nadir >0.5 ng/ml; (2) PSA rise by 0.5 ng/ml; and (3) three consecutive PSA rises. Median follow-up for the brachytherapy group, external beam radiotherapy group, and the radical prostatectomy group was 27, 30 and 36 months respectively. The applied definition influenced reporting of failure rates in two of the three groups. I-125 brachytherapy group: BF rates at 24 months: 46%-definition 1, 35%-definition 2, and 4%-definition 3 (P<0.05). Radiation therapy group: BF rates at 24 months: 39%-definition 1, 17%-definition 2 and 3%-definition 3 (P<0.05). No patient in the radical prostatectomy group had a BF by any applied definition. A more universal definition of BF is needed to compare the efficacy of treatments for localized prostate cancer.     

Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer： the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors

A cure cannot be assured for all men with clinically localized prostate cancer undergoing radical treatment. Molecular markers would be invaluable if they could improve the prediction of occult metastatic disease. This study was carried out to investigate the expression of BCL-2, Ki-67, p53 and E-cadherin in radical prostatectomy specimens. We sought to assess their ability to predict early biochemical relapse in a specific therapeutic setting. Eighty-two patients comprising 41 case pairs were matched for pathological stage, Gleason grade and preoperative prostate-specific antigen （PSA） concentration. One patient in each pair had biochemical recurrence （defined as PSA ≥ 0.2 ng mL^-1 within 2 years of surgery） and the other remained biochemically free of disease （defined as undetectable PSA at least 3 years after surgery）. Immunohistochemical analysis was performed to assess marker expression on four replicate tissue microarrays constructed with benign and malignant tissue from each radical prostatectomy specimen. Ki-67, p53 and BCL-2, but not E-cadherin, were significantly upregulated in prostate adenocarcinoma compared with benign prostate tissue （P 〈 0.01）. However, no significant differences in expression of any of the markers were observed when comparing patients who developed early biochemical relapse with patients who had no biochemical recurrence. This study showed that expression of p53, BCL-2 and Ki-67 was upregulated in clinically localized prostate cancer compared with benign prostate tissue, with no alteration in E-cadherin expression. Biomarker upregulation had no prognostic value for biochemical recurrence after radical prostatectomy, even after considering pathological stage, whole tumour Gleason grade and preoperative serum PSA level.     

11C-choline positron emission tomography for the evaluation after treatment of localized prostate cancer

RATIONALE: The evaluation of the efficacy of the treatment of men with prostate cancer is largely based on post treatment levels of PSA. An increase in PSA or biochemical recurrence is the first sign of recurrent disease and precedes a clinically detectable recurrence by months to years. Digital rectal examination and conventional imaging techniques are not sensitive to detect a local recurrence. A metabolic imaging technique, which is not dependent on anatomical distortions, could be of use. In this study we investigated 11C-choline positron emission tomography (PET) for the evaluation after treatment of localized prostate cancer. METHODS: Thirty-six patients with localized prostate cancer, treated by either radical prostatectomy (n=20) or by external beam radiotherapy (n=16) were studied with 11C-choline PET. The results of PET were compared with the results of histology and with clinical follow up. RESULTS: Fourteen patients had no biochemical failure after therapy. 11C-choline PET was true negative in 14/14 patients. Twenty-two patients had a biochemical failure. In the radical prostatectomy patients 11C-choline PET was true positive in 5/13 (38%) cases. In the external beam radiotherapy patients 11C-choline PET was true positive in 7/9 (78%). The recurrent tumor was confirmed by biopsy or by bone scan in eleven of the twelve true positive patients. In ten patients with a negative 11C-choline PET scan, no recurrent tumor could be proven yet clinically, by biopsy or during follow up. CONCLUSION: 11C-choline PET is a feasible technique for evaluation of treatment for localized prostate cancer. The site of recurrence was detected correctly in 78% of the patients after external beam radiotherapy compared to 38% of the patients after radical prostatectomy. No positive PET scans were observed sofar in patients with a serum PSA <5ng/ml. Confirmatory studies and longer follow up are needed to determine the efficacy of 11C-choline PET compared to other imaging techniques.