Prostatic Neoplasms: Wei JT

Kawachi MH, Bahnson RR, Barry M, Carroll PR, Carter HB, Catalona WJ, Epstein JI, Etzioni RB, Hemstreet GP, Howe RJ, Kopin JD, Lange PH, Lilja H, Mohler J, Moul J, Nadler RB, Patterson S, Pollack A, Presti JC, Stroup AM, Urban DA, Wake R, Wei JT, Anonymous00333. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #17692177 No free full text.

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Wei JT. · No affiliation provided · Cancer. · Pubmed #18186494 links to  free full text

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Uzzo RG, Wei JT. · No affiliation provided · Semin Urol Oncol. · Pubmed #11828351 No free full text.

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Wei JT, Montie JE. · No affiliation provided · Cancer. · Pubmed #10918148 links to  free full text

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Hollenbeck BK, Dunn RL, Wei JT, Sandler HM, Sanda MG. · Division of Urology, Beth Israel-Deaconess Medical Center, Rabb 440, 330 Brookline Avenue, Boston, MA 02215, USA. · Curr Urol Rep. · Pubmed #15161570 No free full text.

Abstract: Each of the three most common contemporary treatments for localized prostate cancer, radical prostatectomy, external beam radiotherapy, and brachytherapy, can have adverse effects on sexual health. Sexual health outcome can be improved by treatment-specific factors, such as the use of nerve-sparing technique during radical prostatectomy, or worsened by the use of androgen deprivation before external beam radiotherapy or brachytherapy. Contemporary studies that have used validated questionnaires to evaluate multiple components of patient-reported sexuality following prostate cancer treatments provide benchmarks of sexual outcome expectations that are of interest to patients selecting their prostate cancer treatment.

Leak B, Wei JT, Gabel M, Peabody JO, Menon M, Demers R, Tewari A. · Vattikuti Urology Institute, Henry Ford Health System, Ann Arbor, MI, USA. · Semin Urol Oncol. · Pubmed #11828356 No free full text.

Abstract: Prostate cancer remains the most commonly diagnosed noncutaneous malignancy in American men. Currently, there are 3 standard treatment options available to men with early prostate cancer: expectant management, radiation therapy, and radical prostatectomy. Although a number of studies have evaluated survival after treatment for early prostate cancer, the optimal choice of therapy for any given patient remains a difficult decision and requires the consideration of a variety of patient and tumor factors. The final selection of therapy for early prostate cancer should be based on an informed discussion between the physician and patient. To accomplish this goal, patients must be made familiar with the pertinent factors that affect survival. We review the factors most relevant for patients to understand as they consider their treatment options for early prostate cancer and summarize the data for physicians who counsel them.

Tewari A, Porter C, Peabody J, Crawford ED, Demers R, Johnson CC, Wei JT, Divine GW, O'Donnell C, Gamito EJ, Menon M. · Vattikuti Urology Institute and Josephine Ford Cancer Center, Henry Ford Hospital, Detroit, Michigan, USA. · Mol Urol. · Pubmed #11790275 No free full text.

Abstract: A number of new predictive modeling techniques have emerged in the past several years. These methods can be used independently or in combination with traditional modeling techniques to produce useful tools for the management of prostate cancer. Investigators should be aware of these techniques and avail themselves of their potentially useful properties. This review outlines selected predictive methods that can be used to develop models that may be useful to patients and clinicians for prostate cancer management.

Montie JE, Wei JT. · Section of Urology, The University of Michigan, Ann Arbor, Michigan 48109-0330, USA. · Cancer. · Pubmed #11309763 links to  free full text

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Cooney KA, Strawderman MS, Wojno KJ, Doerr KM, Taylor A, Alcser KH, Heeringa SG, Taylor JM, Wei JT, Montie JE, Schottenfeld D. · Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA. · Urology. · Pubmed #11164150 No free full text.

Abstract: OBJECTIVES: Previous studies have observed higher age-specific serum prostate-specific antigen (PSA) values in African-American (AA) men without prostate cancer compared to white men, leading some to recommend race-specific PSA reference ranges for the early detection of prostate cancer. The primary objective of the Flint Men's Health Study was to determine age-specific PSA reference values in a community-based sample of AA men, aged 40 to 79 years. METHODS: A probability sample of 943 AA men was selected from households in Genesee County, Michigan. Men without a prior history of prostate cancer/surgery were invited to participate in a prostate cancer screening protocol, consisting of measurement of serum total PSA, free/total PSA ratio, and digital rectal examination. Sextant biopsies were recommended, based on total PSA greater than 4.0 ng/mL and/or an abnormal digital rectal examination. RESULTS: From the sample of 943 men, 732 were eligible, 432 had blood drawn for PSA testing, and 374 completed all phases of the clinical examination. The 95th percentile PSA values were estimated to range from 2.36 ng/mL for men in the fifth decade to 5.59 ng/mL for men in the eighth decade. The 95th percentile values for age-specific PSA were comparable to those observed in a similar study of white men in Olmsted County, Minnesota. The median and 5th percentile values for free/total PSA did not vary significantly across age. CONCLUSIONS: The minor differences in PSA reference ranges between AA and white men may not be of sufficient magnitude to recommend the use of race-specific PSA reference ranges for screening.

Montie JE, Wei JT. · Section of Urology, The University of Michigan, Ann Arbor 48109-0330, USA. · Cancer. · Pubmed #10870046 links to  free full text

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Wei JT, Gross M, Jaffe CA, Gravlin K, Lahaie M, Faerber GJ, Cooney KA. · Robert Wood Johnson Clinical Scholars Program, American Foundation for Urologic Disease and Prostate Quality Enhancement Research Initiative of the Department of Veterans Affairs, Ann Arbor, Michigan, USA. · Urology. · Pubmed #10510915 No free full text.

Abstract: OBJECTIVES: Advanced prostate cancer is a frequently diagnosed condition in the aging male population, and many men will ultimately be treated with androgen deprivation therapy (ADT). Long-term consequences of ADT on bone mineral density (BMD) have not been systematically studied. We performed a pilot study to test the hypothesis that ADT in patients with prostate cancer results in the measurable loss of BMD. METHODS: A cross-sectional study of 32 men with prostate cancer who were about to begin ADT or who had been receiving ADT for more than 1 year was conducted. BMD was measured by single and dual energy x-ray absorptiometry in the lumbar spine, hip, and forearm. Linear regression analysis was used to estimate the time necessary to develop significant BMD loss in the spine, hip, and forearm regions. RESULTS: Five (63%) of 8 men who had not received ADT and 21 (88%) of 24 men who had received ADT for more than 1 year fulfilled the BMD criteria for osteopenia or osteoporosis at one or more sites. When BMD was compared at each site, men who received ADT for more than 1 year had significantly lower BMD in the lumbar spine than men who had not started treatment (P<0.05). On the basis of regression analysis, an estimated 48 months of ADT would be necessary to develop BMD criteria for osteopenia in the lumbar spine for a man with average BMD at the initiation of therapy. CONCLUSIONS: Pre-existing osteopenia and osteoporosis were common in men with prostate cancer before initiating ADT. Both ADT and the duration of ADT were significantly associated with the loss of BMD in men with prostate cancer.

Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM. · The Michigan Center for Translational Pathology, Ann Arbor, USA. · Nature. · Pubmed #19212411 No free full text.

Abstract: Multiple, complex molecular events characterize cancer development and progression. Deciphering the molecular networks that distinguish organ-confined disease from metastatic disease may lead to the identification of critical biomarkers for cancer invasion and disease aggressiveness. Although gene and protein expression have been extensively profiled in human tumours, little is known about the global metabolomic alterations that characterize neoplastic progression. Using a combination of high-throughput liquid-and-gas-chromatography-based mass spectrometry, we profiled more than 1,126 metabolites across 262 clinical samples related to prostate cancer (42 tissues and 110 each of urine and plasma). These unbiased metabolomic profiles were able to distinguish benign prostate, clinically localized prostate cancer and metastatic disease. Sarcosine, an N-methyl derivative of the amino acid glycine, was identified as a differential metabolite that was highly increased during prostate cancer progression to metastasis and can be detected non-invasively in urine. Sarcosine levels were also increased in invasive prostate cancer cell lines relative to benign prostate epithelial cells. Knockdown of glycine-N-methyl transferase, the enzyme that generates sarcosine from glycine, attenuated prostate cancer invasion. Addition of exogenous sarcosine or knockdown of the enzyme that leads to sarcosine degradation, sarcosine dehydrogenase, induced an invasive phenotype in benign prostate epithelial cells. Androgen receptor and the ERG gene fusion product coordinately regulate components of the sarcosine pathway. Here, by profiling the metabolomic alterations of prostate cancer progression, we reveal sarcosine as a potentially important metabolic intermediary of cancer cell invasion and aggressivity.

Kunju LP, Daignault S, Wei JT, Shah RB. · Department of Pathology, University of Michigan School of Medicine, Ann Arbor, MI 48109, USA. · Hum Pathol. · Pubmed #19144380 No free full text.

Abstract: To better represent the Gleason score of radical prostatectomy, the International Society of Urologic Pathologists Consensus Committee recommends assigning individual Gleason scores to prostate cancer cores submitted in separate containers and/or multiple cores in the same container with site identifiers. However, scenarios where multiple cores are submitted in the same container without site identifiers or labeled "left/right" are common. To assess this scenario, we analyzed 110 extended biopsies containing different Gleason scores with corresponding radical prostatectomy for clinically significant grade differences. Because cores are individually labeled and submitted at our institution, we simulated a scenario of multiple intact cores with different Gleason scores in the same container(s) by analyzing as if submitted in containers labeled "left/right." For each biopsy, a Global (all positive cores averaged as 1 long positive core), Worst, and Largest tumor volume Gleason score was determined and compared with grade of radical prostatectomy using kappa statistics. Biopsies containing core(s) with 3+4 and other core(s) 3+3 were excluded because in this situation, both Global and Worst Gleason score will be always 3+4. The following scenarios were considered clinically significant upgrading: biopsy Gleason score 6 / 3+4 to radical prostatectomy 4+3; biopsy 7 to radical prostatectomy 8-10; biopsy 7 to radical prostatectomy 7 with tertiary Gleason pattern 5. Overall, 51 cases met inclusion criteria. Biopsy Worst Gleason score had the best correlation with radical prostatectomy (kappa agreement of 0.37). Clinically significant upgrading at radical prostatectomy was least with Worst (4%) and highest with Global Gleason score (37%). Upgrading and downgrading were noted in 14% and 8%, respectively, of 59 cases containing core(s) with a Gleason score of 3+4 and other core(s) 3+3, suggesting that any amount of higher Gleason pattern should be recorded. When multiple intact cores are submitted in the same container without specific identifiers, individual cores with cancer should be graded and/or the Worst Gleason score should be recorded.

Schulte RT, Wood DP, Daignault S, Shah RB, Wei JT. · Department of Urology, University of Michigan Medical School, Ann Arbor, Michigan 48109-0330, USA. · Cancer. · Pubmed #18726951 No free full text.

Abstract: BACKGROUND: Focal targeted therapy has been proposed as a potential treatment for localized prostate cancer in an attempt to reduce morbidity. However, these modalities rely heavily on accurate tumor localization to achieve total tumor ablation. In the current study, we sought to examine the ability of contemporary extended pattern prostate biopsy to predict the location of tumors. METHODS: A total of 281 men with prostate cancer detected via a standardized extended pattern biopsy template with at least 12 cores and who subsequently underwent radical prostatectomy were evaluated. Tumor location on biopsy, stratified by laterality and by site (apex vs mid-base prostate), was compared with corresponding locations on the prostatectomy specimen. Generalized estimating equation models were developed to assess the effects of clinical variables on pathologic agreement between biopsy and prostatectomy specimens. RESULTS: Of the 281 prostate biopsies, the positive predictive value (PPV) of right and left needle biopsy was high at 97.3% and 96.7%, respectively. However, the negative predictive value (NPV) was low at 24.7% and 31.3%, respectively. When more specific locations were considered, the NPV improved at the apex. However, this came at a cost to the PPV. Tumor focality on prostatectomy specimen was the only clinical feature found to be significantly and consistently related to pathologic agreement. CONCLUSIONS: Contemporary extended pattern prostate biopsy, although able to diagnose cancers, fails to provide reliable localization of tumors to specific areas of the prostate. Focal therapy, which relies heavily on localization, should only be performed with this caveat in mind.

Megwalu II, Ferguson GG, Wei JT, Mouraviev V, Polascik TJ, Taneja S, Black L, Andriole GL, Kibel AS. · Division of Urology, Washington University School of Medicine, St. Louis, MO 63105, USA. · BJU Int. · Pubmed #18694408 No free full text.

Abstract: OBJECTIVE: To explore the ability of a novel transrectal ultrasonography (TRUS) device (TargetScan, Envisioneering Medical Technologies, St. Louis MO) that creates a three-dimensional map of the prostate and calculates an optimal biopsy scheme, to accurately sample the prostate and define the true extent of disease, as standard TRUS-guided prostate biopsy relies on the operator to distribute the biopsy sites, often resulting in under- and oversampling regions of the gland. PATIENTS AND METHODS: In a multicentre retrospective chart review evaluating patients who had a TargetScan prostate biopsy between January 2006 and June 2007, we determined the overall cancer detection rate in all patients and in subgroups based on prostate specific antigen level, digital rectal examination, and indication for biopsy. We assessed the pathological significance of cancer detected, defined as a Gleason score of > or = 7, positive margins, extracapsular disease or > 20% tumour volume in the prostatectomy specimen. We also evaluated the concordance in Gleason score between the biopsy and prostatectomy specimen. RESULTS: Cancer was detected in 50 (35.7%) of the 140 patients biopsied, including 39 (47.6%) with no previous biopsies. Of 23 prostatectomy specimens, 20 (87%) had pathologically significant disease. The biopsy predicted the prostatectomy Gleason score in 12 patients (52%), overestimated in two (9%), underestimated in eight (35%), and biopsy Gleason score could not be assigned in one (4%). CONCLUSIONS: Template-guided biopsy potentially produces a higher cancer detection rate and more accurate assessment of grade. Prostatectomy specimens did not have a high rate of pathologically insignificant disease.

Spencer BA, Miller DC, Litwin MS, Ritchey JD, Stewart AK, Dunn RL, Gay EG, Sandler HM, Wei JT. · Department of Urology, University of Michigan, Ann Arbor, MI 48109-0759, USA. · J Clin Oncol. · Pubmed #18669460 No free full text.

Abstract: PURPOSE: The commencement of quality-improvement initiatives such as Pay for Performance and the Physician Consortium for Performance Improvement has underscored calls to evaluate the quality of cancer care on a patient level for nationally representative samples. METHODS: We sampled early-stage prostate cancer cases diagnosed in 2000 through 2001 from the American College of Surgeons National Cancer Data Base and explicitly reviewed medical records from 2,775 men (weighted total = 55,160 cases) treated with radical prostatectomy or external-beam radiation therapy. We determined compliance with 29 quality-of-care disease-specific structure and process indicators developed by RAND, stratified by race, geographic region, and hospital type. RESULTS: Overall compliance exceeded 70% for structural and pretherapy disease assessment indicators but was lower for documentation of pretreatment functioning (46.4% to 78.4%), surgical pathology (37.1% to 86.3%), radiation technique (62.6% to 88.3%), and follow-up (55%). Geographic variations were observed as higher compliance in the South Atlantic division than the New England division for having at least one board-certified urologist (odds ratio [OR], 9.2; 95% CI, 1.9 to 45.0), at least one board-certified radiation oncologist (OR, 3.3; 95% CI, 1.2 to 9.0), use of Gleason grading (OR, 4.1; 95% CI, 1.2 to 13.8), and administering total radiation dose >or= 70 Gy (OR, 3.1; 95% CI, 1.6 to 6.1). Teaching/research hospitals and Comprehensive Cancer Centers had higher compliance than Community Cancer Centers, whereas racial differences were not observed for any indicator. CONCLUSION: The significant and unwarranted variations observed for these quality indicators by census division and hospital type illustrate the inconsistencies in prostate cancer care and represent potential targets for quality improvement. The lack of racial disparities suggests equity in care once a patient initiates treatment.

Tomlins SA, Rhodes DR, Yu J, Varambally S, Mehra R, Perner S, Demichelis F, Helgeson BE, Laxman B, Morris DS, Cao Q, Cao X, Andrén O, Fall K, Johnson L, Wei JT, Shah RB, Al-Ahmadie H, Eastham JA, Eggener SE, Fine SW, Hotakainen K, Stenman UH, Tsodikov A, Gerald WL, Lilja H, Reuter VE, Kantoff PW, Scardino PT, Rubin MA, Bjartell AS, Chinnaiyan AM. · Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. · Cancer Cell. · Pubmed #18538735 No free full text.

Abstract: ETS gene fusions have been characterized in a majority of prostate cancers; however, the key molecular alterations in ETS-negative cancers are unclear. Here we used an outlier meta-analysis (meta-COPA) to identify SPINK1 outlier expression exclusively in a subset of ETS rearrangement-negative cancers ( approximately 10% of total cases). We validated the mutual exclusivity of SPINK1 expression and ETS fusion status, demonstrated that SPINK1 outlier expression can be detected noninvasively in urine, and observed that SPINK1 outlier expression is an independent predictor of biochemical recurrence after resection. We identified the aggressive 22RV1 cell line as a SPINK1 outlier expression model and demonstrate that SPINK1 knockdown in 22RV1 attenuates invasion, suggesting a functional role in ETS rearrangement-negative prostate cancers.

Sanda MG, Dunn RL, Michalski J, Sandler HM, Northouse L, Hembroff L, Lin X, Greenfield TK, Litwin MS, Saigal CS, Mahadevan A, Klein E, Kibel A, Pisters LL, Kuban D, Kaplan I, Wood D, Ciezki J, Shah N, Wei JT. · Departments of Surgery, Beth Israel Deaconess Medical Center and Harvard Medical School, Harvard University, Boston, MA 02215, USA. · N Engl J Med. · Pubmed #18354103 links to  free full text

Abstract: BACKGROUND: We sought to identify determinants of health-related quality of life after primary treatment of prostate cancer and to measure the effects of such determinants on satisfaction with the outcome of treatment in patients and their spouses or partners. METHODS: We prospectively measured outcomes reported by 1201 patients and 625 spouses or partners at multiple centers before and after radical prostatectomy, brachytherapy, or external-beam radiotherapy. We evaluated factors that were associated with changes in quality of life within study groups and determined the effects on satisfaction with the treatment outcome. RESULTS: Adjuvant hormone therapy was associated with worse outcomes across multiple quality-of-life domains among patients receiving brachytherapy or radiotherapy. Patients in the brachytherapy group reported having long-lasting urinary irritation, bowel and sexual symptoms, and transient problems with vitality or hormonal function. Adverse effects of prostatectomy on sexual function were mitigated by nerve-sparing procedures. After prostatectomy, urinary incontinence was observed, but urinary irritation and obstruction improved, particularly in patients with large prostates. No treatment-related deaths occurred; serious adverse events were rare. Treatment-related symptoms were exacerbated by obesity, a large prostate size, a high prostate-specific antigen score, and older age. Black patients reported lower satisfaction with the degree of overall treatment outcomes. Changes in quality of life were significantly associated with the degree of outcome satisfaction among patients and their spouses or partners. CONCLUSIONS: Each prostate-cancer treatment was associated with a distinct pattern of change in quality-of-life domains related to urinary, sexual, bowel, and hormonal function. These changes influenced satisfaction with treatment outcomes among patients and their spouses or partners.

Laxman B, Morris DS, Yu J, Siddiqui J, Cao J, Mehra R, Lonigro RJ, Tsodikov A, Wei JT, Tomlins SA, Chinnaiyan AM. · Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA. · Cancer Res. · Pubmed #18245462 links to  free full text

Abstract: Although prostate-specific antigen (PSA) serum level is currently the standard of care for prostate cancer screening in the United States, it lacks ideal specificity and additional biomarkers are needed to supplement or potentially replace serum PSA testing. Emerging evidence suggests that monitoring the noncoding RNA transcript PCA3 in urine may be useful in detecting prostate cancer in patients with elevated PSA levels. Here, we show that a multiplex panel of urine transcripts outperforms PCA3 transcript alone for the detection of prostate cancer. We measured the expression of seven putative prostate cancer biomarkers, including PCA3, in sedimented urine using quantitative PCR on a cohort of 234 patients presenting for biopsy or radical prostatectomy. By univariate analysis, we found that increased GOLPH2, SPINK1, and PCA3 transcript expression and TMPRSS2:ERG fusion status were significant predictors of prostate cancer. Multivariate regression analysis showed that a multiplexed model, including these biomarkers, outperformed serum PSA or PCA3 alone in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.758 for the multiplexed model versus 0.662 for PCA3 alone (P = 0.003). The sensitivity and specificity for the multiplexed model were 65.9% and 76.0%, respectively, and the positive and negative predictive values were 79.8% and 60.8%, respectively. Taken together, these results provide the framework for the development of highly optimized, multiplex urine biomarker tests for more accurate detection of prostate cancer.

Macoska JA, Begley LA, Dunn RL, Siddiqui J, Wei JT, Sarma AV. · Department of Urology, University of Michigan, Ann Arbor, Michigan 48109-0944, USA. · Prostate. · Pubmed #18196514 No free full text.

Abstract: BACKGROUND: The incidence and prevalence of both benign prostatic hypertrophy (BPH) and prostate cancer (PCa) increase with the aging process. Our laboratory recently showed that the chemokines CXCL5 and CXCL12, which normally function as inflammatory mediators, are secreted at higher levels by aging prostate stromal fibroblasts and elicit proliferative responses from both prostate stromal fibroblast and epithelial cells. Because both CXCL5 and CXCL12 are secreted molecules, we hypothesized that their levels in patient serum might serve as biomarkers to distinguish between BPH and PCa. METHODS: Serum CXCL5 and CXCL12 levels were determined using sandwich ELISAs for 51 men demonstrating low serum PSA values of < or =10 ng/ml who underwent diagnostic needle biopsy for the detection of PCa. The bivariate relationship of circulating chemokine levels, age, and disease status in the prostate was tested using the Wilcoxon rank-sum test. RESULTS: Total serum CXCL12 levels were significantly higher for men who were biopsy positive compared to those who were biopsy negative for cancer and histological prostatitis (P = 0.050). Among men who were biopsy negative for PCa, total serum CXCL5 levels were inversely associated with prostate volume and were significantly higher in men with concomitant BPH and histological prostatitis compared to those without evidence of prostatic disease (P < 0.003). CONCLUSIONS: The results of this pilot and feasibility study suggest that serum or plasma CXCL5 and CXCL12 levels may potentially distinguish between BPH and PCa among patients presenting with low serum PSA, and may be useful toward facilitating decisions to perform diagnostic needle biopsy in this patient population.

Taylor BS, Pal M, Yu J, Laxman B, Kalyana-Sundaram S, Zhao R, Menon A, Wei JT, Nesvizhskii AI, Ghosh D, Omenn GS, Lubman DM, Chinnaiyan AM, Sreekumar A. · Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. · Mol Cell Proteomics. · Pubmed #18077443 links to  free full text

Abstract: There is considerable evidence for an association between prostate cancer development and inflammation, which results in autoantibody generation against tumor proteins. This immune system-driven amplification of the autoantibody response to intracellular antigens can serve as a sensitive tool to detect low abundance serum proteomic tumor markers for prostate cancer as well as provide insight into biological processes perturbed during cancer development. Here we examine serum humoral responses in a cohort of 34 patients with either benign prostatic hyperplasia or clinically localized prostate cancer (PCa). The experimental strategy couples multidimensional liquid-phase protein fractionation of localized and metastatic prostate cancer tissue lysates to protein microarrays and subsequent mass spectrometry. A supervised learning analysis of the humoral response arrays generated a parsimonious predictor having 78% sensitivity and 75% specificity in distinguishing PCa from benign prostatic hyperplasia in a cohort of American males with elevated prostate-specific antigen. Enrichment analysis of the PCa-specific humoral signature revealed large scale immune reprogramming mediated by STAT transcription factors and the generation of autoantibodies to enzymes involved in nitrogen metabolism. Meta-analysis of independent prostate cancer gene expression data validated the presence of STAT-induced immunomodulation. Concomitant validation of elevated levels of the nitrogen metabolism pathway was obtained by direct measurement of metabolic levels of glutamate and aspartate in prostate cancer tissues. Thus, in addition to functioning as markers in prostate cancer detection, humoral response profiles can serve as powerful tools revealing pathway dysregulation that might otherwise be suppressed by the complexity of the cancer proteome.

Weizer AZ, Ye Z, Hollingsworth JM, Dunn RL, Shah RB, Wolf JS, Wei JT, Montie JE, Hollenbeck BK. · Department of Urology, University of Michigan, Ann Arbor, Michigan 48109, USA. · Urology. · Pubmed #17656216 No free full text.

Abstract: OBJECTIVES: To study the evolution of surgical margins in robotic prostatectomy (DVP), to ascertain the surgical volume necessary to provide quality cancer care. METHODS: Clinicopathologic data on consecutive DVP patients were abstracted from our institutional database. The primary outcome evaluated was the presence of any positive surgical margin. Surgeon DVP volume was the unit of exposure. A logistic model was fit to measure the association of volume and margin status, adjusting for patient differences. RESULTS: Between November 2001 and August 2005, 193 consecutive patients underwent DVP. Disease and patient characteristics were similar across the levels of surgeon volume. Overall, surgical margins did not dramatically decline over time (first 15 cases, 26% versus cases 81 and beyond, 22%; P = 0.82). However, extensive margins were largely eliminated (first 15 cases, 12% versus cases 81 and beyond, 2%; P = 0.05). After adjusting for preoperative patient differences, the odds of any positive margin among those treated by a surgeon in the highest-volume group was 0.99 (95% confidence interval 0.36 to 2.72) compared with those treated during a surgeon's first 15 cases. CONCLUSIONS: Although extensive surgical margins decline with increasing volume, overall positive margin rates after DVP respond slowly. It seems that cumulative surgeon volume beyond that which can be obtained in the typical urology practice may be needed to obtain ideal margin rates with this new technology.

Miller DC, Spencer BA, Shah RB, Ritchey J, Stewart AK, Gay EG, Dunn RL, Wei JT, Litwin MS. · Department of Urology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, California 90095-1738, USA. · Cancer. · Pubmed #17492683 links to  free full text

Abstract: BACKGROUND: The authors assessed adherence with the College of American Pathologists (CAP) radical prostatectomy (RP) practice protocol in a national sample of men who underwent RP for early-stage prostate cancer. METHODS: Using the National Cancer Data Base, the authors identified a nationally representative sample of 1240 men (unweighted) who underwent RP. For each patient, local cancer registrars performed an explicit medical record review to assess patient-level compliance with surgical pathology report documentation of 7 morphologic criteria (ie, quality indicators). Applying the CAP prognostic factor classification framework, composite measures and all-or-none measures of quality indicator compliance were calculated for the following analytic categories: 1) a strict subset of CAP category I prognostic factors (3 indicators), 2) a broad subset of CAP category I factors (6 indicators), and 3) the full set of 7 indicators. RESULTS: Among a weighted sample of 24,420 patients who underwent RP, compliance with documentation of the CAP category I factors varied from 54% (95% confidence interval [95% CI], 50-58%) for pathologic tumor, lymph node, metastases classification (according to the American Joint Committee on Cancer staging system) to 97% (95% CI, 96-99%) for Gleason score. In composite, RP pathology reports contained 83% (95% CI, 81-84%), 85% (95% CI, 84-87%), and 79% (95% CI, 78-80%) of the recommended data elements measured by the strict CAP category I subset, the broad CAP category I subset, and the full set of 7 indicators, respectively. In contrast to the generally higher composite scores, only 52% (95% CI, 48-56%) and 41% (95% CI, 37-45%) of men who underwent RP had complete documentation in their pathology reports for the strict and broad CAP category I subsets, respectively. CONCLUSIONS: RP surgical pathology reports contained most of the recommended data elements; however, the frequent absence of pathologic stage provides an opportunity for quality improvement.

Miller DC, Spencer BA, Ritchey J, Stewart AK, Dunn RL, Sandler HM, Wei JT, Litwin MS. · Department of Urology, University of Michigan, Ann Arbor, USA. · Med Care. · Pubmed #17446826 No free full text.

Abstract: BACKGROUND: Variations in patterns of care and treatment outcomes suggest differences in the quality of care for men treated for localized prostate cancer. OBJECTIVE: We sought to compare adherence with quality indicators for prostate cancer care among men treated with radical prostatectomy or external beam radiation therapy. RESEARCH DESIGN AND SUBJECTS: We sampled 5230 men diagnosed in 2000 or 2001 with early-stage prostate cancer from 984 facilities reporting to the National Cancer Data Base. Our analytic cohort includes 2604 men (from 770 facilities) treated with radical prostatectomy or external beam radiation. MAIN OUTCOME MEASURE: Subject-level compliance with the RAND quality indicators for localized prostate cancer care, stratified by treatment. We applied sampling weights to obtain national estimates of quality indicator adherence. RESULTS: The weighted samples represent 24,547 and 27,125 men treated with radical prostatectomy or external beam radiation therapy, respectively. Compliance with several quality indicators approached 100% in both treatment groups; however treatment-specific variations were noted. Men receiving radiation were less likely than those undergoing surgery to be treated in facilities with a board-certified urologist (odds ratio [OR] = 0.4, 95% confidence interval [95% CI] = 0.2-0.8). Adherence with process of care indicators was appreciably higher among radiation subjects, including documentation of clinical stage (OR = 7.5, 95% CI = 4.8-11.9), pretherapy assessment of urinary (OR = 2.8, 95% CI = 1.9-4.2) and sexual (OR = 1.6, 95% CI = 1.2-2.2) function, and discussion of treatment options (OR = 1.8, 95% CI = 1.1-2.9). CONCLUSIONS: Documented compliance with process of care quality indicators among men with localized prostate cancer appears superior for those treated with external beam radiation compared with those treated surgically.

Lee IH, Roberts R, Shah RB, Wojno KJ, Wei JT, Sandler HM. · Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #17398032 No free full text.

Abstract: PURPOSE: To determine if perineural invasion (PNI) should be included in addition to prostate-specific antigen (PSA), biopsy Gleason score, and clinical T-stage for risk-stratification of patients with localized prostate cancer. METHODS AND MATERIALS: We analyzed prostatectomy findings for 1550 patients, from a prospectively collected institutional database, to determine whether PNI was a significant predictor for upgrading of Gleason score or pathologic T3 disease after patients were stratified into low-, intermediate-, and high-risk groups (on the basis of PSA, biopsy Gleason score, and clinical T-stage). RESULTS: For the overall population, PNI was associated with a significantly increased frequency of upgrading and of pathologic T3 disease. After stratification, PNI was still associated with significantly increased odds of pathologic T3 disease within each risk group. In particular, for low-risk patients, there was a markedly increased risk of extraprostatic extension (23% vs. 7%), comparable to that of intermediate-risk patients. Among high-risk patients, PNI was associated with an increased risk of seminal vesicle invasion and lymph node involvement. Furthermore, over 80% of high-risk patients with PNI were noted to have an indication for postoperative radiation. CONCLUSIONS: Perineural invasion may be useful for risk-stratification of prostate cancer. Our data suggest that low-risk patients with PNI on biopsy may benefit from treatment typically reserved for those with intermediate-risk disease. In addition, men with high-risk disease and PNI, who are contemplating surgery, should be informed of the high likelihood of having an indication for postoperative radiation therapy.