Biomedical subjects

Shahrokh F Shariat

Publications and source records attributed to Shahrokh F Shariat.

At least 55 records · Page 3Linked to original sources

PubMed2004

Molecular diagnosis of prostate cancer.

The diagnosis, staging, and management of prostate cancer as we know it today is greatly dependent on our ability to measure serum prostate-specific antigen (PSA) concentration. Nevertheless, because serum PSA concentration, particularly when less than 10 ng/mL, reflects the presence of benign prostatic hyperplasia more often than cancer, there is a clear need for more specific prostate cancer markers. The most promising new markers for prostate cancer are the various molecular forms of free PSA. Mass spectrometry also is emerging as a potential tool in prostate cancer screening. Because it is unlikely that any one marker will have 100% sensitivity and specificity, as new serum markers are tested, nomograms that incorporate multiple independently predictive parameters for the detection of prostate cancer will become indispensable in our efforts to improve prostate cancer screening.

Biomarkers, Tumor↗

PubMed2004

Risk stratification for bladder tumor recurrence, stage and grade by urinary nuclear matrix protein 22 and cytology.

PURPOSE: To test the hypothesis that voided urinary levels of nuclear matrix protein 22 (NMP22) would add to the predictive ability of urine cytology in the diagnosis, staging and grading of bladder transitional cell carcinoma (TCC), and to evaluate the diagnostic performance of different NMP22 cut-points. MATERIALS: NMP22 level and barbotage cytology were evaluated in voided urine specimens collected before cystoscopy from 302 subjects with a history of TCC, 32 subjects with benign urologic pathologies, and 10 healthy volunteers. RESULTS: 180 patients (52%) had bladder TCC. Higher levels of NMP22 and positive cytology were independently associated with an increased risk of TCC, invasive stage, and high grade. The NMP22 value with equal sensitivity and specificity for prediction of bladder cancer was 6.5U/ml; for prediction of grade 3 TCC it was 13.5U/ml; and for prediction of invasive tumor stage it was 17.4U/ml. The NMP22 cut-point of 6.5U/ml outperformed the 10U/ml cut-point in all pathologic stages and grades. The diagnostic sensitivity of the cytology and NMP22 combined was superior across all pathologic stages and grades to that of either marker alone. NMP22 and cytology stratified patients into groups with significantly different risk for TCC presence, invasive stage, and high grade. CONCLUSIONS: 6.5U/ml is a robust NMP22 cut-point for bladder cancer surveillance. The diagnostic sensitivities of the combined NMP22 and cytology for TCC presence, stage, and grade were significantly higher than those of single marker alone. The combination of urine cytology and NMP22 could be used to tailor the frequency of cystoscopic follow up.

Adult↗

PubMed2004

Tissue expression of transforming growth factor-beta1 and its receptors: correlation with pathologic features and biochemical progression in patients undergoing radical prostatectomy.

OBJECTIVES: To determine whether the abnormal expression of transforming growth factor-beta1 (TGF-beta1) and/or its receptors (TGFbeta-RI and TGFbeta-RII) is associated with prostate cancer features and progression; and to investigate the relationship between tissue expression of TGFs and blood levels of TGF-beta1. METHODS: Immunohistochemical staining for TGF-beta1, TGFbeta-RI, and TGFbeta-RII was carried out on archival specimens from 118 consecutive patients who underwent radical prostatectomy for clinically localized disease (median follow-up 57.5 months). Preoperative plasma TGF-beta1 levels were also measured. RESULTS: TGF-beta1 was overexpressed in 71 (60%) of 118 patients, and TGFbeta-RI and TGFbeta-RII expression was decreased in 34 (29%) and 39 (33%) of 118 patients, respectively. Of the 118 patients, 82 (70%) had abnormal expression of at least one of the three TGFs and 22 (19%) had abnormal expression of all three. The concordance rates between the expression of TGF-beta1 and its receptors were 54% and 62%. Abnormal expression of all three TGFs was significantly associated with extracapsular disease. However, only decreased expression of TGFbeta-RI and TGFbeta-RII was significantly associated with seminal vesicle involvement and greater pathologic Gleason score. Preoperative plasma TGF-beta1 levels were significantly elevated in patients with abnormal expression of TGFs. TGFbeta-RI expression and surgical margin status were independently associated with biochemical progression. CONCLUSIONS: Our results showed that abnormal expression of TGF-beta1 and its receptors is common in prostate cancer. TGF-beta1 overexpression is moderately but significantly associated with a loss of expression of TGFbeta-RI and TGFbeta-RII. Loss of TGFbeta-RI expression is a prognostic marker in patients with prostate cancer.

Adult↗

PubMed2004

Serum BPSA outperforms both total PSA and free PSA as a predictor of prostatic enlargement in men without prostate cancer.

OBJECTIVES: To determine whether the serum concentration of BPSA, a distinct form of free prostate-specific antigen (PSA) enriched in the nodular transition zone (TZ) tissue of benign prostatic hyperplasia (BPH), can predict TZ volume and diagnose BPH-associated prostatic enlargement in patients without prostate cancer. METHODS: We studied 91 consecutive patients without prostate cancer who underwent a 10-core or greater biopsy of the prostate. The associations between prostate volume, age, International Prostate Symptom Score, and serum concentrations of PSA, free PSA, and BPSA were evaluated by receiver operating characteristic curve and linear and binary logistic regression analyses. RESULTS: BPSA and free PSA showed stronger correlations with both age (BPSA = 0.38, free PSA = 0.40, PSA = 0.24) and TZ volume (BPSA = 0.67, free PSA = 0.64, PSA = 0.55) than did PSA. The percent free PSA had no statistically significant correlation with TZ volume (P = 0.08). Subtraction of BPSA from free PSA reduced its correlation with TZ volume to below that of PSA (from 0.64 to 0.48). Linear regression analyses showed that, unlike PSA, both BPSA and free PSA displayed an age-independent relationship to TZ volume. The receiver operating characteristic curve (for TZ greater than 30 cm3) and binary logistic regression analyses showed that BPSA (area under the curve = 0.844) outperformed both free PSA (area under the curve = 0.799) and PSA (area under the curve = 0.749) in its ability to predict clinically significant TZ enlargement. CONCLUSIONS: In patients without prostate cancer, the serum concentration of BPSA displayed an age-independent, log-linear relationship to TZ volume and was a better predictor of prostatic enlargement than either PSA or free PSA. BPSA may also predict clinical parameters of BPH and is under evaluation as a marker of BPH progression and response to therapy.

Adult↗

PubMed2004

Impact of unilateral interposition sural nerve grafting on recovery of urinary function after radical prostatectomy.

OBJECTIVES: To test the hypothesis that unilateral sural nerve graft (SNG) interposition may improve the rate of urinary function (UF) recovery after radical retropubic prostatectomy (RRP) in patients undergoing unilateral nerve resection (UNR). METHODS: We studied 111 consecutive patients who underwent RRP with purposeful UNR performed by a single surgeon. Of the 111 patients, 53 underwent unilateral SNG interposition. All patients were invited to complete a questionnaire that included the validated University of California, Los Angeles, Prostate Cancer Index. The time to UF recovery above the median value of the group and urinary control status were evaluated. RESULTS: The median follow-up was 26 and 12 months for the UNR and UNR+SNG patients, respectively. At 12 months after RRP, 94.7% of patients with UNR+SNG reported having complete urinary control or leakage of only a few drops of urine compared with 58.3% of patients with UNR alone (P = 0.012). In multivariate Cox regression models, UNR+SNG was associated with a 9.95 times greater rate of reaching a UF score above the median versus UNR alone (P <0.001). In multivariate logistic regression analyses, SNG status increased the odds of having complete urinary control or leakage of only a few drops of urine by 14.99 and 29.19 at 6 and 12 months after RRP, respectively (both P <0.05). CONCLUSIONS: In patients undergoing UNR surgery, SNG interposition is associated with a greater rate of UF recovery and a higher likelihood of urinary control after RRP. These findings need to be validated in larger, multicenter, prospective, randomized studies.

Aged↗

PubMed2004

Six additional systematic lateral cores enhance sextant biopsy prediction of pathological features at radical prostatectomy.

PURPOSE: We evaluated the contribution of 6 additional systematically obtained, laterally directed biopsy cores to traditional sextant biopsy for the prediction of final pathological findings in the radical prostatectomy specimen. MATERIALS AND METHODS: We studied 178 consecutive patients with no history of prostate biopsy in whom prostate cancer was diagnosed during an initial systematic 12 core biopsy and who subsequently underwent radical prostatectomy. Of the systematic 12 cores we compared the subset of the 6 traditional sextant cores (S6C), the set of 6 laterally directed cores (L6C) and the complete 12 core set, which included the 6 traditional sextant and the 6 laterally directed cores. Biopsy Gleason score, number of positive cores, total cancer length and percent of tumor in the biopsy sets were examined for their ability to predict extracapsular extension, total tumor volume and pathological Gleason score. RESULTS: On univariable analyses the biopsy parameters of the complete 12 core set correlated more strongly with extracapsular extension and total tumor volume than the biopsy parameters of S6C or L6C. On multivariable analyses S6C and L6C were independent predictors of pathological features at prostatectomy. CONCLUSIONS: The addition of 6 systematically obtained, laterally directed cores to traditional sextant biopsy improved the ability to predict pathological features at prostatectomy by a statistically and prognostically significant margin. Preoperative nomograms that use data from a full complement of 12 systematic cores, specifying sextant and laterally directed biopsy cores, should demonstrate improved performance in predicting prostatectomy pathology.

Aged↗

PubMed2004

Urine detection of survivin is a sensitive marker for the noninvasive diagnosis of bladder cancer.

PURPOSE: In a preliminary study urine detection of survivin, an integrator of cell death and mitosis, accurately detected bladder cancer. The objectives of this study were to confirm these findings in a large cohort of subjects undergoing cystoscopy, to assess the diagnostic performance of urine survivin and to test whether evaluation of urine survivin adds independent value to urine NMP22 (Matritech, Cambridge, Massachusetts) and cytology for the detection of bladder cancer. MATERIALS AND METHODS: Urine survivin was measured using a Bio-Dot microfiltration detection system (Bio-Rad, Hercules, California) in voided urine specimens collected before cystoscopy in 117 cases and 92 controls. Bladder washout samples for cytology were collected in 174 subjects. Urine levels of NMP22 were measured using a commercially available enzyme-linked immunosorbent assay. RESULTS: Higher levels of urine survivin were associated with an increased risk of bladder cancer (p <0.001) and tumors of higher grade (p = 0.037), but not with invasive stage, after adjustment for the effects of urine cytology, NMP22 and age. The sensitivity, specificity, and positive and negative predictive values of survivin for the diagnosis of bladder cancer (64%, 93%, 92% and 67%, respectively), are superior to those of NMP22 and cytology. Survivin had the highest specificity and positive predictive value for the detection of bladder cancer across each tumor stage and grade. CONCLUSIONS: Urine survivin was a strong, independent predictor of the presence of bladder cancer and higher tumor grade. Urine detection of survivin is an accurate diagnostic test for bladder cancer that retains its efficiency regardless of cancer stage and grade.

Adult↗

PubMed2004

Improved detection of clinically significant, curable prostate cancer with systematic 12-core biopsy.

PURPOSE: While systematic 12-core (S12C) biopsy detects more cancers than sextant biopsy, to our knowledge the clinical significance of these additionally detected tumors has not been established. We studied pathological parameters of prostatectomy specimens from patients undergoing radical prostatectomy for prostate cancer detected with a S12C biopsy to determine the clinical significance of these cancers in comparison with sextant detected cancers. MATERIALS AND METHODS: A total of 179 consecutive patients undergoing radical prostatectomy for clinically localized prostate cancer detected by S12C biopsy were studied. The groups compared consisted of the sextant core subset of the S12C and the entire S12C set. Total tumor volume, Gleason score, organ confined status, surgical margin status, seminal vesicle invasion, lymph node involvement, and clinical significance of tumors detected by sextant and by S12C templates were compared. RESULTS: S12C biopsy detected a greater number of cancers scored as moderate (Gleason score 2 to 6) or high (Gleason score 7 or greater) grade, and cancers of all sizes regardless of organ confined status than the sextant cores alone (all p <0.05). S12C biopsy identified a greater number of biologically significant and insignificant tumors regardless of how they were defined. CONCLUSIONS: Compared with the sextant set S12C biopsy detects a significantly greater number of surgically curable, biologically significant tumors as well as those that might be considered clinically insignificant.

Aged↗

PubMed2004

Lymphovascular invasion is a pathological feature of biologically aggressive disease in patients treated with radical prostatectomy.

UNLABELLED: We examined whether invasion of lymphatic and/or vascular vessels (LVI), or perineural spaces (PNI) is associated with prostate cancer features and outcome. MATERIALS AND METHODS: A total of 630 consecutive men underwent radical retropubic prostatectomy for clinically localized disease. LVI and PNI examination was part of the routine specimen evaluation. RESULTS: Foci of LVI were identified in 32 patients (5%) and 381 (60.5%) had PNI. LVI and PNI were associated with clinical stage T2 disease, higher biopsy and final Gleason sum, extraprostatic extension, seminal vesicle involvement, positive surgical margins and a higher percent of positive biopsy cores (p <0.001). LVI was associated with metastases to regional lymph nodes and higher preoperative serum prostate specific antigen (p <0.001 and 0.004, respectively). PNI and LVI were associated with an increased risk of rapid biochemical progression after radical prostatectomy on univariate (p <0.001 and 0.001, respectively) but not on multivariate analysis. LVI was associated with shorter prostate specific antigen doubling time after biochemical progression (p = 0.012) and higher probabilities of failed local salvage radiation therapy (p = 0.0169), distant metastases (p <0.001) and death (p <0.001). CONCLUSIONS: Only LVI is associated with metastases to regional and distant sites, and most importantly with overall survival. LVI and PNI are associated with established markers of biologically aggressive disease and rapid biochemical progression in patients who underwent radical prostatectomy. Our findings support the routine evaluation of LVI status in radical prostatectomy specimens and its inclusion in predictive models for clinical outcomes, since it appears to be a pathological marker of the lethal phenotype of prostate cancer.

Adult↗

PubMed2004

Predictors of prostate cancer after initial negative systematic 12 core biopsy.

PURPOSE: We determined the cancer detection rate at initial systematic 12 core (S12C) biopsy and identified features associated with cancer at repeat S12C biopsy after an initial negative S12C biopsy in patients with prostate specific antigen (PSA) parameters associated with a higher risk of prostate cancer. MATERIALS AND METHODS: Between February 1999 and June 2002, 841 patients underwent initial S12C biopsy. Of these patients 99 underwent repeat S12C biopsy after initial negative S12C because of a percent free-to-total PSA of 15.0 or less and/or a yearly PSA velocity of 0.75 ng/ml or greater. The association between parameters revealed by initial biopsy and cancer at repeat biopsy was assessed. RESULTS: Of the 99 patients 21 (21.2%) had cancer at repeat biopsy. Age (p = 0.01), PSA transitional zone density (p = 0.05), and high grade PIN at initial biopsy (p = 0.01) were associated with cancer at repeat biopsy. CONCLUSIONS: In this select group of patients with PSA parameters associated with a higher risk of prostate cancer the cancer detection rate after initially negative S12C biopsy was 21%. Patients with high grade PIN on initial biopsy, advanced age and higher PSA transition zone density are at increased risk for cancer at repeat biopsy. Larger prospective studies are required to confirm these results and construct a nomogram that determines the probability of finding prostate cancer at subsequent biopsy.

Biopsy, Needle↗

PubMed2004

Stage specific lymph node metastasis mapping in radical cystectomy specimens.

PURPOSE: We provide an accurate map of lymph node (LN) metastasis in patients with bladder cancer undergoing radical cystectomy and pelvic lymph node dissection. MATERIALS AND METHODS: We analyzed data on 176 consecutive patients operated on by the same surgeon. The extent of node dissection included presacral, bilateral common iliac and pelvic, and perivesical. The number of LNs removed from each site and the number of metastases bearing nodes were recorded separately. Stage specific maps were constructed. RESULTS: The median number of LNs removed was 25 (range 2 to 80). Metastases were found in the lymph nodes of 43 patients (24.4%) and the median number of positive nodes was 3 (range 1 to 63). Of these patients 22 (51%) had lymph node involvement at more than 1 site. The mean number of positive/total LNs sampled +/- SD in LN positive cases was 26% +/- 28% and the median was 13% (range 1.9 to 100%). Only 1 of the patients with pT1 (3.6%) had LN metastases, which was in the pelvic region. Only 2 of the patients with pT2 (3%) had LN metastases outside of the true pelvis and perivesical sites. Of patients with pT3 or pT4 16% had LN metastases outside the common boundaries for standard LN dissection, namely the common iliac artery and at or above aortic bifurcation. CONCLUSIONS: We present a detailed map of regional LN involvement in patients treated with radical cystectomy and lymph node dissection for transitional cell cancer of the bladder. Extensive LN dissection is essential for the complete removal of disease and accurate staging.

Adult↗

PubMed2004

The percent of biopsy cores positive for cancer is a predictor of advanced pathological stage and poor clinical outcomes in patients treated with radical prostatectomy.

PURPOSE: We examined if the percent of positive biopsies is associated with features of biologically aggressive prostate cancer, biochemical progression and development of distant metastases in patients undergoing radical prostatectomy (RP). MATERIALS AND METHODS: Multivariate analyses of preoperative features in 605 consecutive patients who underwent RP for clinically localized disease were evaluated to determine the association between the percent positive biopsy cores (PosBx), pathological stage and grade, and biochemical progression following RP. The percent of PosBx cores was defined using the formula, (number of positive biopsy cores/total number of biopsy cores) x 100. RESULTS: The mean number of biopsy cores and percent PosBx cores +/- SE was 8.8 +/- 6.0 and 31.4 +/-21.1, respectively. Higher percent PosBx was significantly associated with higher preoperative prostate specific antigen (PSA), extracapsular extension, seminal vesicle invasion, positive surgical margins, higher final Gleason sum, lymphovascular invasion, perineural invasion and metastases to regional lymph nodes. On multivariate analyses adjusted for the effects of standard preoperative features percent PosBx was associated with nonorgan confined disease, seminal vesicle invasion and biochemical progression after surgery (p = 0.049, 0.050 and 0.006, respectively). Percent PosBx retained its independent association with PSA progression after adjustment for the effects of postoperative pathological features (p = 0.015). Higher percent PosBx was associated with shorter PSA doubling time after PSA progression, and an increased risk of distant metastases and overall mortality (p = 0.039, 0.001 and 0.018, respectively). CONCLUSIONS: Percent PosBx is associated with established pathological features, biochemical progression, distant metastases and overall death in patients who undergo RP for clinically localized disease. Percent PosBx should be included in preoperative predictive models for prognosticating outcomes after primary treatment and it may assist in selecting patients for inclusion in neoadjuvant and/or adjuvant therapy trials.

Adult↗

PubMed2004

Variation in prostate specific antigen results from 2 different assay platforms: clinical impact on 2304 patients undergoing prostate cancer screening.

PURPOSE: Urologists must contend with fluctuating prostate specific antigen (PSA) results from different assay platforms when deciding whether prostate biopsy is indicated. The contribution of cross-platform variation to these fluctuations is not well understood. To address this question we performed a cross-sectional study comparing 2 popular PSA assays during prostate cancer screening. MATERIALS AND METHODS: The Baylor College of Medicine Prostate Cancer Screening Program is a community outreach program providing free screening to Houston residents. From September 18th to 23, 2000, 2,304 patients underwent digital rectal examination and parallel serum PSA assay by the Hybritech Access (Beckman Coulter, Inc., Chaska, Minnesota) and Centaur (Bayer Diagnostics, Tarrytown, New York) systems. The Wilcoxon signed ranks test was used to compare results. RESULTS: Median PSA was low for the 2 assays (Centaur 0.99 ng/ml and Access 1.09 ng/ml) and Access results were significantly higher (1.23 times) than those obtained with Centaur (p <0.001). Frozen serum from 50 patients with PSA greater than 2.5 were then re-assayed using a third methodology (third Generation Immulite, Diagnostic Products Corp., Los Angeles, California). These data were consistent with Centaur results and significantly lower than Access results (p <0.001). Using a cutoff of PSA greater than 4.0 ng/ml 55 of the 288 patients (19%) with PSA greater than 2.5 ng/ml on the 2 platforms would have been candidates for prostate biopsy based on Access but not on Centaur data. CONCLUSIONS: In a large screening population the Access system measured consistently higher PSA than the Centaur system. These findings provide a basis for interpreting PSA results obtained from 2 commonly used clinical assays.

Adult↗

PubMed2004

Effects of systematic 12-core biopsy on the performance of percent free prostate specific antigen for prostate cancer detection.

PURPOSE: The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. MATERIALS AND METHODS: We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. RESULTS: Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). CONCLUSIONS: The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.

Aged↗

PubMed2004

Predictive value of primary Gleason pattern 4 in patients with Gleason score 7 tumours treated with radical prostatectomy.

OBJECTIVE: To examine whether Gleason score (GS) 3 + 4 and 4 + 3 cancers at radical prostatectomy behave differently and whether this behaviour is independently associated with prostate cancer outcome. PATIENTS AND METHODS: From July 1994 to December 2002 309 consecutive men who had a radical retropubic prostatectomy for clinically localized disease had final GS 7 tumours in their prostatectomy specimen. Statistical analyses, including multivariate logistic regression, were used to evaluate the association between variables, i.e. standard preoperative features, stage, PSA progression, standard pathological variables, metastasis and death. RESULTS: In all, 215 patients (70%) had a final GS of 3 + 4 and 94 (30%) of 4 + 3. A final GS of 4 + 3 was associated with clinical stage T2 disease (P = 0.024), a higher biopsy GS (P < 0.001), seminal vesicle involvement (P < 0.001), positive surgical margins (P = 0.036), lymphovascular invasion (P = 0.018), metastases to regional lymph nodes (P = 0.008), higher preoperative serum prostate-specific antigen (PSA) (P = 0.042), and percentage positive biopsy cores (P = 0.006). In univariate analysis, patients with GS 4 + 3 had a significantly higher risk of biochemical progression than those with GS 3 + 4 (P = 0.002). The 5-year actuarial risk of biochemical progression was 17% and 35% for GS 3 + 4 and 4 + 3, respectively (P = 0.0016). In a standard postoperative multivariate analysis, only preoperative PSA and metastases to regional lymph nodes were associated with PSA progression (P < 0.001 and 0.002, respectively). However, patients with final GS 4 + 3 had a shorter PSA doubling time after progression than those with GS 3 + 4 (P = 0.009). CONCLUSIONS: Tumours with a final GS of 4 + 3 are more aggressive than GS 3 + 4 tumours. Recognising the distinction in GS 7 between predominant 4 vs 3 scores after radical prostatectomy should improve the ability of clinicians to counsel patients. The GS 4 pattern deserves further molecular study.

Adult↗

PubMed2004

Beyond prostate-specific antigen: new serologic biomarkers for improved diagnosis and management of prostate cancer.

The use of total prostate-specific antigen (tPSA) measurement has dramatically improved the ability to detect prostate cancer at earlier stages. However, as the number of men presenting with advanced disease (and high tPSA levels) has decreased, and given the fact that tPSA is highly reflective of benign prostatic hyperplasia, the need has emerged for novel biomarkers specifically associated with prostate cancer in order to improve predictive models. Several new biomarkers have shown promise, and studies continue to investigate the role of these markers in the detection, staging, and prognosis of prostate cancer. As new useful biomarkers continue to emerge, guidelines for their employment, as well as coordination of further research studies, are needed; a systematic, phased, nomogram-based model is a rational way to manage these efforts.

Journal Article↗

PubMed2003

Early postoperative peripheral blood reverse transcription PCR assay for prostate-specific antigen is associated with prostate cancer progression in patients undergoing radical prostatectomy.

Preoperative peripheral blood reverse transcription-PCR (RT-PCR) for prostate-specific antigen (PSA) [RT-PCR-PSA] is not associated with an increased risk of progression after radical prostatectomy. We tested the hypothesis that early postoperative peripheral blood RT-PCR-PSA would detect prostate cancer cells persisting in the circulation that would be associated with disease progression. The study group consisted of 145 consecutive patients who underwent radical prostatectomy for clinically localized disease (median follow-up, 54.5 months) for whom pre- and postoperative peripheral blood samples were available. RT-PCR-PSA was performed on preoperative and postoperative peripheral blood specimens. Pre- and postoperative RT-PCR-PSA were positive in 27% and 12%, respectively, of patients. Most (64%) preoperative RT-PCR-PSA-positive patients converted to a negative RT-PCR-PSA status after prostate removal (P < 0.001). Whereas preoperative RT-PCR-PSA was not associated with prostate cancer characteristics or outcome, a positive postoperative RT-PCR-PSA assay was associated with extracapsular extension (P = 0.044) and seminal vesicle involvement (P = 0.024). Furthermore, postoperative RT-PCR-PSA was an independent predictor of disease progression (P = 0.027). In patients who experienced disease progression, postoperative RT-PCR-PSA was associated with a more aggressive pattern of failure (P = 0.005). Whereas a significant number of patients with clinically localized prostate cancer have prostate cells detectable preoperatively by RT-PCR-PSA circulating in their blood, most of these cells are clinically insignificant because the majority of these patients convert to RT-PCR-PSA-negative status and maintain disease-free status after prostate removal. In contrast, postoperative RT-PCR-PSA detection of prostate cells in the peripheral blood is associated with established markers of aggressive prostate cancer and is an early independent predictor of disease progression, presumably because of an association with established micrometastatic disease.

Adenocarcinoma↗

PubMed2003

The addition of interleukin-6 soluble receptor and transforming growth factor beta1 improves a preoperative nomogram for predicting biochemical progression in patients with clinically localized prostate cancer.

PURPOSE: Several preoperative prostate cancer nomograms have been developed that predict risk of progression using pretreatment prostate-specific antigen (PSA) level, clinical stage, and biopsy Gleason grade. We describe the development and performance of a new nomogram. The nomogram adds new markers to the standard clinical predictors that reflect the biologic behavior of prostate cancer: pretreatment plasma levels of interleukin-6 soluble receptor (IL6SR) and transforming growth factor beta1 (TGF-beta1). PATIENTS AND METHODS: Between November 7, 1994 and December 22, 1997, 714 patients with stage cT1c to cT3a prostate cancer and no prior therapy were treated with radical prostatectomy at the Methodist Hospital, Houston TX. Plasma levels of IL6SR and TGF-beta1 were measured in banked preoperative plasma. With these data, a nomogram was developed to predict the probability of PSA progression within 5 years of surgery. The nomogram was validated with bootstrapping to assess its discrimination and calibration performance. RESULTS: In the multivariable Cox model, PSA (P =.004), IL6SR (P <.001), TGF-beta1 (P <.001), primary Gleason grade (P <.002), and secondary Gleason grade (P =.029) were associated with PSA progression, whereas clinical stage (P =.696) was not. The nomogram seemed to be well calibrated and had a bootstrap-corrected area under the receiver operating characteristic curve (ie, concordance index) of 0.83. For comparison, a nomogram that omitted IL6SR and TGF-beta1 achieved a concordance index of only 0.75. CONCLUSION: We found that pretreatment plasma levels of IL6SR and TGF-beta1 improved the ability to predict biochemical progression by a prognostically substantial margin. A nomogram including the pretreatment levels of these molecular markers, along with standard clinical markers, has been developed and internally validated.

Adult↗