Use of the Prostate Health Index for detection of prostate cancer: results from a large academic practice.

BACKGROUND: The Prostate Health Index (phi) outperforms PSA and other PSA derivatives for the diagnosis of prostate cancer (PCa). The impact of phi testing in the real-world clinical setting has not been previously assessed. METHODS: In a single, large, academic center, phi was tested in 345 patients presenting for diagnostic evaluation for PCa. Findings on prostate biopsy (including Grade Group (GG), defined as GG1: Gleason score (GS) 6, GG2: GS 3+4=7, GG3: GS 4+3=7, GG4: GS 8 and GG5: GS 9-10), magnetic resonance imaging (MRI) and radical prostatectomy (RP) were prospectively recorded. Biopsy rates and outcomes were compared with a contemporary cohort that did not undergo phi testing (n=1318). RESULTS: Overall, 39% of men with phi testing underwent prostate biopsy. No men with phi<19.6 were diagnosed with PCa, and only three men with phi<27 had cancer of GG⩾2. Phi was superior to PSA for the prediction of any PCa (area under the receiver operating characteristic curve (AUC) 0.72 vs 0.47) and GG⩾2 PCa (AUC 0.77 vs 0.53) on prostate biopsy. Among men undergoing MRI and phi, no men with phi<27 and PI-RADS⩽3 had GG⩾2 cancer. For those men proceeding to RP, increasing phi was associated with higher pathologic GG (P=0.002) and stage (P=0.001). Compared with patients who did not undergo phi testing, the use of phi was associated with a 9% reduction in the rate of prostate biopsy (39% vs 48%; P<0.001). Importantly, the reduction in biopsy among the phi population was secondary to decreased incidence of negative (8%) and GG1 (1%) biopsies, whereas the proportion of biopsies detecting GG⩾2 cancers remained unchanged. CONCLUSIONS: In this large, real-time clinical experience, phi outperformed PSA alone, was associated with high-grade PCa, and provided complementary information to MRI. Incorporation of phi into clinical practice reduced the rate of unnecessary biopsies without changing the frequency of detection of higher-grade cancers.

Clinical prospects of long noncoding RNAs as novel biomarkers and therapeutic targets in prostate cancer.

BACKGROUND: The lack of sensitive and specific biomarkers for prostate cancer (PCa) has led to over-diagnosis and overtreatment with uncertain benefit. Therefore, biomarkers for early diagnosis that can distinguish aggressive from indolent tumors and that can detect metastatic or recurrent disease are needed. Long noncoding RNAs (lncRNAs) are non-protein-coding RNA species. lncRNAs are dysregulated in many diseases including PCa and are emerging as major players in cancer development. lncRNAs have several features that make then suitable as both biomarkers and therapeutics, and lncRNAs regulate critical cancer hallmarks in prostate epithelial cells including proliferation and survival. METHODS: The PubMed database was searched using the terms 'long noncoding RNA', 'biomarker' and 'prostate cancer'. Known lncRNAs implicated as biomarkers and potential therapeutic targets in PCa are reviewed. RESULTS: We comprehensively review several lncRNAs with potential as biomarkers for PCa. lncRNAs including PCA3, PCATs, SChLAP1, SPRY4-IT1 and TRPM2-AS are upregulated in PCa and are cancer specific; they are, therefore, attractive lead candidate biomarkers for clinical application. Several lncRNA therapeutics are currently being investigated by several companies for the treatment of various cancers including PCa. Small interfering RNAs, antisense oligonucleotides, ribozymes, deoxyribozymes and aptemers are few promising technologies for future lncRNA bases therapeutics. CONCLUSION: lncRNA expression is altered in cancer. Aberrant regulation promotes tumor formation, progression and metastasis. lncRNAs can use as tumor markers for PCa and may be attractive novel therapeutic targets for the diagnosis and treatment of PCa.

Very-high-risk localized prostate cancer: definition and outcomes.

BACKGROUND: Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy. METHODS: We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage ≥T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort. RESULTS: The VHR cohort was best defined by primary pattern 5 present on biopsy, or ≥5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%). CONCLUSIONS: Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.

Metastasis-free survival is associated with overall survival in men with PSA-recurrent prostate cancer treated with deferred androgen deprivation therapy.

BACKGROUND: Clinical trials in men with biochemically recurrent prostate cancer (BRPC) have been hampered by long survival times, making overall survival (OS) a difficult end point to reach. Intermediate end points are needed in order to conduct such trials within a more feasible time frame. PATIENTS AND METHODS: This is a retrospective analysis of 450 men with BRPC following prostatectomy treated at a single institution between 1981 and 2010, of which 140 developed subsequent metastases. Androgen deprivation therapy (ADT) was deferred until after the development of metastases. Cox regression models were developed to investigate factors influencing OS. RESULTS: Median metastasis-free survival (MFS) was 10.2 years [95% confidence interval (CI) 7.6-14.0 years]; median OS after metastasis was 6.6 years (95%CI 5.8-8.4 years). Multivariable Cox regressions identified four independently prognostic variables for OS: MFS (HR 0.77; 95% CI 0.63-0.94), number of metastases (≤3 versus ≥4; HR 0.50; 95% CI 0.29-0.85), pain (absent versus present; HR 0.43; 95% CI 0.25-0.72), and bisphosphonate use (yes versus no; HR 0.60; 95% CI 0.37-0.98). CONCLUSIONS: MFS emerged as an independent predictor of OS in men with BRPC treated with deferred ADT after the development of metastases. MFS may be a reasonable intermediate end point in future clinical trials. This observation requires prospective validation.

Prevalence of BPH and lower urinary tract symptoms in West Africans.

BACKGROUND: BPH and lower urinary tract symptoms (LUTS) are very common among older men in Western countries. However, the prevalence of these two conditions in the developing countries is less clear. METHODS: We assessed the age-standardized prevalence of BPH and/or LUTS among West Africans in a probability sample of 950 men aged 50-74 in Accra, Ghana, with no evidence of biopsy-confirmed prostate cancer after screening with PSA and digital rectal examination (DRE). Information on LUTS was based on self-reports of the International Prostate Symptom Score (IPSS). BPH was estimated using DRE, PSA levels and imputed prostate volume. RESULTS: The prevalence of DRE-detected enlarged prostate was 62.3%, while that of PSA≥1.5 ng ml(-1) (an estimate of prostate volume ≥ 30 cm(3)) was 35.3%. The prevalence of moderate-to-severe LUTS (IPSS≥8) was 19.9%. The prevalence of IPSS≥8 and an enlarged prostate on DRE was 13.3%. Although there is no universally agreed-upon definition of BPH/LUTS, making comparisons across populations difficult, BPH and/or LUTS appear to be quite common among older Ghanaian men. CONCLUSIONS: We found that after age standardization, the prevalence of DRE-detected enlarged prostate in Ghanaian men is higher than previously reported for American men, but the prevalence of LUTS was lower than previously reported for African Americans. Further studies are needed to confirm these findings and identify the risk factors for BPH in both Africans and African Americans.

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

PURPOSE: Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. MATERIALS AND METHODS: We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. RESULTS: Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in group 1 (23 of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who were known to harbor prostate carcinoma. The proportion of early prostate cancer antigen positivity was statistically significantly lower in group 2 than in each of the other groups when compared pairwise. A lower proportion of early prostate cancer antigen positivity was encountered in older archival tissue blocks (p<0.0001) pointing to a potential confounding factor. Corrected for block age, group 3 was the only group to remain statistically significantly different in early prostate cancer antigen positivity compared to the reference group 2. Similar findings were obtained when adjustments for patient age were made and when analysis was based on secondary outcome measurements. CONCLUSIONS: Our study showed a higher proportion of early prostate cancer antigen expression in initial negative prostate biopsy of patients who were diagnosed with prostate carcinoma on subsequent followup biopsies. We found a relatively high proportion of early prostate cancer antigen positivity (59%) in the group with first time negative biopsies and a potential 41% rate of false-negative early prostate cancer antigen staining in benign biopsies from cases with documented prostate carcinoma on concurrent cores. The lower early prostate cancer antigen positivity in cases with older blocks raises the question of a confounding effect of block age. Additional studies on the antigenic properties of early prostate cancer antigen in archival material are required to further delineate the usefulness of early prostate cancer antigen immunostaining on biopsy material.

Expectant management: an option for localized prostate cancer.

Localized prostate cancer demonstrates tremendous heterogeneity in the natural history of the disease. To this end, although prostate cancer may be present histologically in nearly 30% of all men above the age of 50 y, the lifetime risk of developing clinically significant disease is 18% (one in six). Furthermore, the lifetime risk of dying from prostate cancer is less than 4%. Therefore, in order to avoid unnecessarily treating potentially insignificant prostate cancer, the concept of expectant management has been considered for this disease. In this brief review, we discuss the evolution of expectant management for men with localized prostate cancer.

The effect of hospital volume on cancer control after radical prostatectomy.

PURPOSE: For complex oncological procedures, hospital volume affects short and long-term patient outcome. We examined the association of hospital volume and long-term cancer control after radical prostatectomy. MATERIALS AND METHODS: With a cohort study design, we used the Surveillance, Epidemiology and End Results-Medicare linked files to identify a population based sample of men with newly diagnosed prostate cancer treated primarily with radical prostatectomy. Failure of cancer control was defined as the use of postoperative medical or surgical hormone ablation or treatment with radiation therapy more than 6 months after surgery. RESULTS: A total of 12,635 men underwent radical prostatectomy for incident prostate cancer. After adjusting for age, comorbidity, histological grade and clinical stage, the risk of adjuvant therapy was greater among those treated at low (1 to 33 cases) and medium (34 to 61 cases) volume hospitals than at very high (more than 108 cases) volume hospitals (HR 1.25, p <0.001 and HR 1.11, p =0.023 respectively). CONCLUSIONS: Patients treated at lower volume institutions are at increased risk of initiation of subsequent adjuvant therapy with radiation therapy, medical hormone ablation or orchiectomy. Noted differences in cancer control provide additional evidence regarding issues surrounding the debate over surgical volume standards for the surgical treatment of prostate cancer.

Stromal-epithelial measurements of prostate cancer in native Japanese and Japanese-American men.

We measured the histologic stromal and epithelial tissue components of the benign (normal) and malignant tissue compartments of Japanese-Americans (J-A) and native Japanese (NJ) men living in Japan. The patient cohort included 25 NJ men undergoing radical prostatectomy (RP) in Nagoya, Japan and 25 J-A (second or third generation US born). We conducted tissue image quantitation (in-house image software) of the stromal and epithelial compartments in malignant and adjacent normal tissue areas from a tissue microarray (TMA) selected from radical prostatectomy (RP) blocks. Stromal-epithelial (S-E) areas were determined using immunohistochemical stains for CAM-5.2 epithelial cytokeratin marker and the Masson trichrome stain to measure the stroma component. We observed differences in the volumes of normal and cancer epithelium and stroma within both the J-A and NJ study populations (P<0.01). Only the individual average cancer epithelium (CE) volume (JA=24.1 vs NJ=29.9) differed significantly between the NJ and J-A study populations (P=0.03). Consequently, the S-E ratio in NJ group was significantly different from that of J-A population (P=0.05). The decrease in S-E ratio noted in the malignant tissues of NJ prostate tissue may provide a biological marker for differentiation of the two groups and suggests a need for further investigations into the molecular basis for these histologic differences.

Proteomic analysis of dunning prostate cancer cell lines with variable metastatic potential using SELDI-TOF.

BACKGROUND: Surface enhanced laser desorption and ionization-time-of-flight (SELDI-TOF) is an evolving proteomic technology for improving biomarker discovery that allows for rapid and sensitive analysis of complex protein mixtures generated from body fluids, cells, and/or tissues. SELDI--based profiling identifies unique, differentially expressed proteins relating to specific cancer-related disease states. We utilized SELDI-TOF following pre-processing with molecular separation and chemical fractionation of cell membrane extracts from three Dunning rat prostate cancer cell lines of varying metastatic potential to search novel proteins that are differentially expressed. METHODS: Dunning rat cell sublines of variable (%) metastatic potential; G (0%), AT-1 (20%), and Mat-Ly-Lu (100%) were cultured in two different laboratories. Cell lysis was performed in a homogenation buffer (320 mM sucrose/50 mM Tris/0.5 mM PSMF) using Dounce homogenation. After centrifugation, the membrane pellet was washed 2x and then solublized in 2% CHAPS/8 M urea. This sample was further processed using positive pressure molecular ultrafiltration at 30 kDa or precipitation with 50% ammonium sulfate. Next, each sample was applied to an IMAC3-Ni ProteinChip (Ciphergen Biosystems, Freemont, CA) and analyzed using Ciphergen's Protein Biology System with protein peak analysis software. RESULTS: SELDI-TOF analysis differentiated the three Dunning rat cell sublines based upon protein concentration normalized profiles between 5,000 and 20,000 Da. The preparations from the three cells lines showed clear differences when the extracts from the metastatic sublines (AT-1 and MLL) were compared to the benign subline (G) for proteins with molecular weights of 9 kDa (decrease), 12 kDa (significant decrease), 14 kDa (decrease), and 17 kDa (significant gain). After pre-processing extracts with ammonium sulfate and molecular ultrafiltration, the molecular profile changes from one subline to the next became more apparent. Our results were reproducible using multiple runs including from Dunning cells cultured in a separate laboratory, and using different lots of SELDI ProteinChips. CONCLUSIONS: The application of SELDI-TOF to a series of Dunning rat prostate cancer cell lines illustrated apparent changes in protein profiles among the three cell lines with known differences in metastatic biologic activity. SELDI-TOF identified four reproducible changes in protein expression in the AT1 and MLL metastatic cell sublines. Three of the expression changes were manifested as decreases, but one protein (17 kDa) was over-expressed in the AT1 and MLL cell lines. Emphasis will be placed on the isolation, purification, and characterization of the 17 kDa over-expressed protein and its potential role in PCa metastasis.

Contemporary update of prostate cancer staging nomograms (Partin Tables) for the new millennium.

OBJECTIVES: We previously presented nomograms combining preoperative serum prostate-specific antigen (PSA), clinical (TNM) stage, and biopsy Gleason score to provide the likelihood of various final pathologic stages at radical retropubic prostatectomy. The data for the original nomograms were collected from men treated between 1982 and 1996. During the past 10 years, the stage at presentation has shifted, with more men presenting with Stage T1c, Gleason score 5 to 6, and serum PSA levels less than 10.0 ng/mL. In this work, we update the "Partin Tables" with a more contemporary cohort of men treated since 1994 and with revised PSA and Gleason categories. METHODS: Multinomial log-linear regression analysis was used to estimate the likelihood of organ-confined disease, extraprostatic extension, seminal vesicle or lymph nodal status from the preoperative PSA stratified as 0 to 2.5, 2.6 to 4.0, 4.1 to 6.0, 6.1 to 10.0, and greater than 10 ng/mL, clinical (AJCC-TNM, 1992) stage (T1c, T2a, T2b, or T2c), and biopsy Gleason score stratified as 2 to 4, 5 to 6, 3 + 4 = 7, 4 + 3 = 7, or 8 to 10 among 5079 men treated with prostatectomy (without neoadjuvant therapy) between 1994 and 2000 at Johns Hopkins Hospital. The average age was 58 years. RESULTS: In this cohort, more than 60% had T1c, more than 75% had Gleason score of 6, more than 70% had PSA greater than 2.5 and less than 10.0 ng/mL, and more than 60% had organ-confined disease. Nomograms of the robust estimated likelihoods and 95% confidence intervals were developed from 1000 bootstrap analyses. The probability of organ-confined disease improved across the groups, and further stratification of the Gleason score and PSA level allowed better differentiation of individual patients. CONCLUSIONS: These updated "Partin Tables" were generated to reflect the trends in presentation and pathologic stage for men newly diagnosed with clinically localized prostate cancer at our institution. Clinicians can use these nomograms to counsel individual patients and help them make important decisions regarding their disease.

Does capsular incision at radical retropubic prostatectomy affect disease-free survival in otherwise organ-confined prostate cancer?

OBJECTIVES: To evaluate the influence of isolated, histologically identified capsular incision (CI) (exposure of benign or malignant glands to the inked surgical margin in the setting of organ-confined disease) on disease progression after anatomic radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. METHODS: Between March 1993 and September 1999, 4747 men underwent RRP at the Johns Hopkins Hospital; 107 men (2.3%) were diagnosed with CI in otherwise organ-confined disease; 92 (86%) had at least 6 months (mean 30) of follow-up. We matched these CI cases (based on surgeon, age, clinical stage, final pathologic Gleason grade, and preoperative serum prostate-specific antigen level) one-for-one with controls in three additional pathologically defined groups and compared the freedom from disease progression (prostate-specific antigen level greater than 0.2 ng/mL and/or local palpable recurrence) after RRP. RESULTS: The actuarial 3-year likelihood of freedom from disease progression was 87.8% for the CI group, 96.4% for men with organ-confined disease (P = 0.10), 91.3% for men with extraprostatic extension and negative surgical margins (P = 0.99), and 73.9% for men with positive surgical margins resulting from extraprostatic extension (P <0.01). No statistically significant difference was found in the actuarial likelihood of freedom from disease progression between men with CI into benign glands (n = 22) and men with CI into tumor (n = 70) (P = 0.93). CONCLUSIONS: No statistically significant difference was found in the likelihood of early recurrence between patients with isolated CI and other specimen-confined disease. Patients with isolated CI have a significantly lower likelihood of early recurrence than patients with positive surgical margins due to extraprostatic extension, regardless of whether the CI is into benign glands or tumor. Long-term follow-up is necessary to confirm these findings.

Indicators of pathologic stage of prostate cancer and their use in clinical practice.

Pathologic stage is the most reliable means of predicting the likelihood of curable prostate cancer at the time of definitive treatment. Its prediction is of the greatest importance to individuals with clinically localized disease, principally because of the therapeutic and prognostic implications. Multivariate models integrating variables that can be derived from clinical and pathologic assessment have been shown to be reliable and useful in urologic practice. Among these variables, the combination of clinical stage, serum PSA, and biopsy Gleason score provides reliable assessment of the risk for extraprostatic disease that can be used readily for counseling individual patients. Other biopsy-derived parameters may contribute additional information, but their value in multivariate analysis has not been validated in a multi-institutional setting. The development of new prognostic markers is a priority objective in current research to distinguish patients in whom cancer cannot be controlled by surgical treatment. For patients undergoing radical prostatectomy, definitive pathologic stage certainly will remain an important prognostic factor; therefore, clinical practice will continue to be determined by its accurate prediction.

Long-term biochemical disease-free and cancer-specific survival following anatomic radical retropubic prostatectomy. The 15-year Johns Hopkins experience.

In a large series of 2404 men with a mean follow-up of 6.3 plus or minus 4.2 years (range, 1-17) after anatomic RRP for clinically localized prostate cancer, 412 men (17%) have recurred. A detectable PSA was the only evidence of recurrence in 9.7%, whereas 1.7% and 5.8% had local recurrence and distant metastasis, respectively. The overall actuarial 5-, 10-, and 15-year recurrence-free survival rates for these men were 84%, 74%, and 66%, respectively. As demonstrated in the authors' previous reports, the actuarial likelihood of a postoperative recurrence increased with advancing clinical stage, Gleason-score, preoperative PSA level, and pathologic stage. Subdivision of men with Gleason 7 tumors resulted in better stratification. There was a similar actuarial likelihood of postoperative recurrence for men with Gleason 4 + 3 and Gleason score 8 to 10 disease. The actuarial rate of recurrence of tumor for men with Gleason 3 + 4 disease was statistically different from the rate for men with Gleason score 6 or Gleason 4 + 3 disease. The overall actuarial metastasis-free survival rates at 5, 10, and 15 years were 96%, 90%, and 82%, respectively. The overall actuarial cancer-specific survival rates at 5, 10, and 15 years were 99%, 96%, and 90%, respectively. This study provides long-term outcome of patients with clinically localized cancer who underwent RRP between 1982 and 1999. Recognizing that this long-term study includes many patients with more advanced disease diagnosed before the PSA era, caution must be exercised in comparing these results with the outcomes for cohorts of patients treated since 1989. Anatomic RRP is an effective way to manage clinically localized prostate cancer. Excellent long-term results can be obtained with RRP for early stage disease. The proportion of men with early stage prostate cancer will continue to increase with wide use of serum PSA testing and digital rectal examination.

Safety and efficacy of exisulind for treatment of recurrent prostate cancer after radical prostatectomy.

PURPOSE: We evaluated the safety and efficacy of exisulind for delaying disease progression in men with increasing prostate specific antigen (PSA) after radical prostatectomy. MATERIALS AND METHODS: A total of 96 men with increasing PSA after radical prostatectomy were randomized to receive placebo (49) or 250 mg. exisulind twice daily (47) for 12 months. The primary efficacy parameter was the difference in change from baseline PSA between the placebo and exisulind groups. The PSA doubling time was also evaluated before and during study. A subgroup analysis classified patients based on the risk of developing metastatic disease. RESULTS: Compared with placebo, exisulind significantly suppressed the increase in PSA in all patients (p = 0.017). The results were also statistically significant in men at high risk for metastasis (p = 0.0003) and those who could not be classified according to risk (p = 0.0009). In addition, median PSA doubling time was lengthened in high risk patients on exisulind (2.12 month increase) compared with those on placebo (3.37 month decrease, p = 0.048). Exisulind was well tolerated. CONCLUSIONS: Exisulind inhibited the increase in PSA overall and prolonged PSA doubling time in high risk patients compared with placebo. These results suggest that Exisulind has the potential to extend the time from biochemical recurrence to the need for androgen deprivation therapy. Exisulind was well tolerated in this patient population. Our results support further study of Exisulind in the treatment of patients with prostate cancer.

Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We retrospectively reviewed a large series of men with clinically localized prostate cancer who underwent surgery to define the extent of stage migration and its influence on biochemical recurrence in 3 different eras of prostate cancer management. MATERIALS AND METHODS: A total of 2,370 men were treated with radical prostatectomy from 1982 to 1998. We analyzed the freedom from biochemical (prostate specific antigen) progression after radical prostatectomy. We compared the distribution of pathological stage by the year of surgery. We then compared the biochemical recurrence-free survival rate according to the different eras that reflect a change in prostate cancer management. RESULTS: There was a significant downward stage migration of prostate cancer and an increasing proportion of men who presented with organ confined disease in recent years. The actuarial biochemical recurrence-free rate was significantly different for patients who underwent surgery between 1982 and 1988, compared with those between 1989 and 1998 (p <0.001). These changes may have reflected the benefits of early detection with prostate specific antigen and digital rectal examination, better preoperative selection of patients for surgery as well as the effect of lead time. CONCLUSIONS: Widespread early detection programs for prostate cancer resulted in downward stage migration in men presenting with prostate cancer at our institution during the last 18 years. Also, we have demonstrated a biochemical recurrence-free survival advantage, probably secondary to an improved therapeutic outcome as well as lead time bias, in men who underwent surgery between 1989 and 1998, compared with those between 1982 and 1988. When trying to compare the efficacy of different treatment modalities for prostate cancer, the era in which patients underwent therapy is an important factor to be considered.