Prostatic Neoplasms: Freedland SJ

Arlen PM, Bianco F, Dahut WL, D'Amico A, Figg WD, Freedland SJ, Gulley JL, Kantoff PW, Kattan MW, Lee A, Regan MM, Sartor O, Anonymous00032. · Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland 20892, USA. · J Urol. · Pubmed #18423743 links to  free full text

Abstract: PURPOSE: Prostate specific antigen is a glycoprotein found almost exclusively in normal and neoplastic prostate cells. Prostate specific antigen doubling time, or the change in prostate specific antigen over time, has emerged as a useful predictive marker for assessing disease outcome in patients with prostate cancer. It is important to agree on definitions and values for the calculation of prostate specific antigen doubling time, and to develop a common approach to outcome analysis and reporting. MATERIALS AND METHODS: In September 2006 a conference was held at the National Cancer Institute in Bethesda, Maryland to define these parameters and develop guidelines for their use. RESULTS: The Prostate Specific Antigen Working Group defined criteria regarding prostate specific antigen doubling time including the calculation of prostate specific antigen doubling time, evidence to support prostate specific antigen doubling time as a predictive factor in the setting of biochemical recurrence and the use of prostate specific antigen doubling time as a stratification factor in clinical trials. CONCLUSIONS: We propose that investigators calculate prostate specific antigen doubling time before enrolling patients in clinical studies and calculate it as an additional measurement of therapeutic activity. We believe we have developed practical guidelines for the calculation of prostate specific antigen doubling time and its use as a measurement of prognosis and outcome. Furthermore, the use of common standards for prostate specific antigen doubling time in clinical trials is important as we determine which treatments should progress to randomized trials in which "hard" end points such as survival will be used.

Hamilton RJ, Freedland SJ. · No affiliation provided · Eur Urol. · Pubmed #17985423 No free full text.

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Freedland SJ. · No affiliation provided · J Urol. · Pubmed #17868740 No free full text.

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Aronson WJ, Freedland SJ, Freeland SJ. · No affiliation provided · J Urol. · Pubmed #10604334 No free full text.

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Jayachandran J, Freedland SJ. · Department of Surgery, Veterans Administration Medical Center Durham, Durham, North Carolina 27710, USA. · Am J Mens Health. · Pubmed #19477782 No free full text.

Abstract: As one of the most prevalent cancers, prostate cancer has enormous public health importance and its prevention seems to be a rational approach to attenuate the economic, emotional, physical, and social impact of this disease. This review discusses some of the options available to clinicians worldwide under the broad headings of chemoprevention and dietary modification including lifestyle issues. From the review of available literature, it is appreciated that although many exciting options such as androgen inhibitors, vitamin E, and selenium are being actively considered, they are far from being included in clinical practice. So until large randomized trials confirm the benefit of chemopreventives and dietary modifications, patients may be advised to pursue a diet and lifestyle that ensures overall fitness.

Freedland SJ, Aronson WJ. · Department of Surgery, Durham VA Medical Center, Durham, North Carolina, USA. · Curr Opin Urol. · Pubmed #19300265 No free full text.

Abstract: PURPOSE OF REVIEW: There is increasing interest in complementary and holistic approaches for cancer prevention and management. We sought to review the latest literature regarding dietary interventions for prostate cancer with a special emphasis on dietary fat and carbohydrate intake for modulating prognosis among men with prostate cancer. RECENT FINDINGS: Several recent prospective trials have investigated various dietary and lifestyle investigations on malignant prostate tissue biology. These interventions included a very low-fat (12% fat kcals) vegan diet with various supplements and lifestyle changes, a more traditional low-fat diet (25% fat kcals) with flaxseed supplementation, and a low-glycemic index diet. Low-glycemic index and very low-fat vegan diets (with supplements and lifestyle changes) alter tumor biology as assessed by tumor gene expression changes, with a common mechanism perhaps being weight loss whereas no effects were seen with a traditional low-fat diet. In mice, either very low-fat or low-carbohydrate diets significantly slow tumor growth independent of weight loss. Epidemiologic and preclinical data also suggest cholesterol intake and serum cholesterol levels may be linked with the development and progression of prostate cancer. SUMMARY: Small clinical trials suggest that tumor biology can be altered by either a vegan low-fat diet or eliminating simple carbohydrates accompanied by weight loss. Larger and longer term studies are needed to determine the clinical relevance of these findings.

Antonelli J, Freedland SJ, Jones LW. · Division of Urologic Surgery, Department of Surgery, Duke Prostate Center, Duke University Medical Center, Durham, NC 27710, USA. · Prostate Cancer Prostatic Dis. · Pubmed #19274062 No free full text.

Abstract: Exercise has been increasingly investigated as an adjunct therapy for cancer patients. The purpose of this paper is to comprehensively review the literature regarding exercise as a therapeutic adjunct for prostate cancer (PC). Several studies in patients with PC have shown quality of life improvements associated with exercise. Although no study has established the effect of exercise as a monotherapy for PC, the molecular mechanisms responsible for the potential association between exercise and PC are being elucidated. Given the low-risk, high-reward nature of these studies, further investigations are needed to better define the function of exercise along the PC continuum.

Hamilton RJ, Freedland SJ. · Division of Urology, Duke University School of Medicine, Box 2626, Duke University Medical Center, Durham, NC 27710, USA. · Curr Urol Rep. · Pubmed #18765112 No free full text.

Abstract: The potential ability of statin medications to prevent cancer has recently received considerable attention. Of all cancers studied, data for prostate cancer are the most promising. Results from studies examining the association between statin use and reduced risk of prostate cancer have been encouraging, particularly in terms of advanced prostate cancer risk. These findings are supported by a strong foundation of scientific evidence demonstrating the potential cholesterol and non-cholesterol-mediated mechanisms through which statins may prevent prostate cancer. In this article, we analyze recent human data regarding the association between statins and prostate cancer, and the basic scientific data supporting the possible antineoplastic mechanisms of statins. We also address the issue of where to best direct future funding and research energies. There is currently insufficient evidence to recommend all men to initiate therapy with a statin medication regardless of cholesterol profile, but the rationale to move forward with research is clear.

Hamilton RJ, Freedland SJ. · Division of Urology, Department of Surgery, University of Toronto, Toronto, Ontario, Canada. · Curr Opin Urol. · Pubmed #18382245 No free full text.

Abstract: PURPOSE OF REVIEW: We examine the potential chemopreventive role statins may have in prostate cancer, highlight the basic science supporting this role and analyze the human data regarding the association between statin use and prostate cancer. RECENT FINDINGS: Basic scientific evidence suggests that, through cholesterol and noncholesterol-mediated mechanisms, statins inhibit many pathways of cancer formation and progression. A handful of observational studies found statin use was associated with reduced prostate cancer risk, though others found no association. In the last year, however, four large prospective studies have observed similar reductions in the risk of advanced prostate cancer with essentially no reduction in the risk of overall prostate cancer. This may, in part, explain why previous studies, including large metaanalyses of clinical trials of statins in the prevention of cardiovascular outcomes, did not observe any association between statin use and overall prostate cancer risk. SUMMARY: The exact association between statin medication use and prostate cancer, and whether this association is causal in nature, remains unclear. Recent evidence, however, is encouraging, particularly for reducing the risk of advanced disease. Thus, while at present there are insufficient data to recommend all men start taking a statin medication regardless of their cholesterol profile, the rationale to move forward with further research is clear.

Moul JW, Bañez LL, Freedland SJ. · Division of Urologic Surgery, Duke Prostate Center, Duke University Medical Center,Durham, NC 27710, USA. · Oncology (Williston Park). · Pubmed #18077992 No free full text.

Abstract: Rising prostate-specific antigen (PSA) in nonmetastatic prostate cancer occurs in two main clinical settings: (1) rising PSA to signal failed initial local therapy and (2) rising PSA in the setting of early hormone-refractory prostate cancer prior to documented clinical metastases. Most urologists and radiation oncologists are very familiar with the initial very common clinical scenario, commonly called "biochemical recurrence." In fact, up to 70,000 men each year will have a PSA-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear and includes salvage local therapies and systemic approaches, of which the mainstay is hormonal therapy. Treatment needs to be individualized based upon the patient's risk of progression and the likelihood of success and the risks involved with the therapy. It is unknown how many men per year progress with rising PSA while on hormonal therapy without documented metastases. This rising PSA disease state is sometimes called, "PSA-only hormone-refractory prostate cancer." As in the setting of initial biochemical recurrence, evidence-based treatment options are limited, and taking a risk-stratified approach is justified. In this article, we will explore these prostate cancer disease states with an emphasis on practical, clinically applicable approaches.

Freedland SJ, Moul JW. · Division of Surgery, Durham Veterans Affairs Medical Center, Durham, NC, USA. · J Urol. · Pubmed #17509277 No free full text.

Abstract: PURPOSE: We estimate that approximately 70,000 men yearly have prostate specific antigen-only recurrence after failed definitive therapy. The ideal salvage therapy for these men is not clear. Treatment must be individualized based on the patient risk of progression, the likelihood of success and the risks involved with the therapy. However, to do so the risks and benefits of the various options must be known. Therefore, we provide a comprehensive overview of the natural history and treatment options for men with prostate specific antigen-only recurrence. MATERIALS AND METHODS: A literature review and overview of prostate specific antigen-only recurrence after failed definitive therapy was done. RESULTS: The natural history after prostate specific antigen-only recurrence is long but variable. Median time from prostate specific antigen-only recurrence after radical prostatectomy to prostate cancer death exceeds 16 years, although some men die within 1 year after PSA recurrence. Rapid prostate specific antigen doubling time is the best prognostic factor for poor outcome. Salvage radiation therapy after radical prostatectomy results in a 45% 4-year prostate specific antigen response rate, although long-term outcomes appear poor. To our knowledge the effect on survival is not known. Salvage radical prostatectomy is rarely performed but in the highly selected patient it may provide some benefit. There are no randomized studies of early vs late hormonal therapy for men with prostate specific antigen-only recurrence. A retrospective study suggested delayed metastasis when therapy was begun early but only in men at high risk. This mirrors other data suggesting that men at high risk may derive significant benefits from early hormonal therapy, whereas men at low risk are unlikely to benefit and may be harmed by hormonal therapy. CONCLUSIONS: Prostate specific antigen-only recurrence is the most common form of advanced prostate cancer. Optimal salvage treatments and timing of these treatments remain controversial.

Buschemeyer WC, Freedland SJ. · Department of Surgery, Veterans Administration Medical Center Durham, Durham, NC, USA. · Eur Urol. · Pubmed #17507151 No free full text.

Abstract: OBJECTIVES: Both obesity and prostate cancer (PCa) are epidemic in Western society. Although initial epidemiological data appeared conflicting, recent studies have clarified the association between obesity and PCa. Therefore, we sought to review the epidemiological data linking obesity and PCa with an emphasis on the clinical implications and how to improve outcomes among obese men. METHODS: A PubMed search using the keywords "prostate cancer" and "obesity" was performed. Relevant articles and references were reviewed for data on the association between obesity and PCa. RESULTS: Recent data suggest obesity is associated with reduced risk of nonaggressive disease but increased risk of aggressive disease. This observation may be explained in part by an inherent bias in our ability to detect PCa in obese men (lower PSA values and larger sized prostates, making biopsy less accurate for finding an existent cancer), which ultimately leads to increased risk of cancer recurrence after primary therapy and increased PCa mortality. Despite this detection bias potentially contributing to more aggressive cancers, multiple biological links also exist between obesity and PCa including higher estradiol, insulin, free IGF-1, and leptin levels, and lower free testosterone and adiponectin levels, all of which may promote more aggressive cancers. CONCLUSIONS: The association between obesity and PCa is complex. Emerging data suggest obesity increases the risk of aggressive cancer, while simultaneously decreasing the risk of more indolent disease. This is likely driven by both "biological" and "nonbiological" causes. Simple changes in clinical practice patterns can reduce the impact of nonbiological causes and may help improve PCa outcomes among obese men.

Freedland SJ, Platz EA. · Department of Surgery, Veterans Affairs Medical Center, Durham, NC 27710, USA. · Epidemiol Rev. · Pubmed #17478439 No free full text.

Abstract: Both obesity and prostate cancer are epidemic in Western society. Although initial epidemiologic data appeared conflicting, recent studies, especially large prospective studies published in the past 6-12 months, have clarified the association between obesity and prostate cancer. The aim of this paper is to review the epidemiologic data linking obesity and prostate cancer, with an emphasis on new data published since 2005. A PubMed search was done on the keywords, "prostate cancer" and "obesity." Relevant articles and their references were reviewed for data on the association between obesity and prostate cancer. Recent data suggest that obesity is associated with reduced risk of nonaggressive disease but increased risk of aggressive disease. This may in part be explained by an inherent bias in our ability to detect prostate cancer in obese men (lower prostate-specific antigen values and larger sized prostates making biopsy less accurate for finding an existing cancer). Ultimately, this leads to increased risk of cancer recurrence after primary therapy and increased risk of prostate cancer mortality. The biologic causes of these associations are likely multifactorial, although the lower testosterone levels among obese men appear to be one of the most promising explanations. The association between obesity and prostate cancer is complex. Emerging data suggest a differential effect of obesity by disease aggressiveness: obesity may reduce the risk of nonaggressive disease while it may promote aggressive disease.

Mavropoulos JC, Isaacs WB, Pizzo SV, Freedland SJ. · Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA. · Urology. · Pubmed #16844447 No free full text.

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Freedland SJ, Krupski TL, Moul JW. · Department of Surgery, Division of Urology, Duke University School of Medicine, Durham, NC 27710, USA. · Curr Opin Urol. · Pubmed #16679854 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this review is to summarize single-institution prostate-cancer-outcomes databases (which are most commonly derived from large academic medical centers, Veterans Affairs medical centers, and military hospitals) to summarize the design and development of three well characterized outcomes databases that combine data from multiple sites (Carcinoma of the Prostate Strategic Urological Research Endeavor, Center for Prostate Disease Research, and the Shared Equal Access Regional Cancer Hospital database) and to use the examples of obesity and prostate-specific antigen changes over time to highlight the importance of these databases in prostate-cancer outcomes. RECENT FINDINGS: Multiple databases have demonstrated that obese men are at greater risk of biochemical progression following radical prostatectomy. In addition, objective data have shown that it is more difficult to operate on obese men leading to greater risk of positive surgical margins, which may contribute to poorer outcomes. Several databases have shown that a rapidly increasing prostate-specific antigen, measured either before diagnosis or after failed primary therapy, is associated with increased risk of prostate-cancer-specific mortality. SUMMARY: Outcomes databases are extremely useful tools. They have lead to dramatic improvements of our understanding of prostate cancer. The challenge is to use this information from past patients to help us better manage our current and future patients.

Freedland SJ, Partin AW. · Division of Urology, Department of Surgery, Duke University School of Medicine, Durham, North Carolina 27710, USA. · Urology. · Pubmed #16504254 No free full text.

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Freedland SJ, Giovannucci E, Platz EA. · James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Cancer Causes Control. · Pubmed #16411047 No free full text.

Abstract: Recent studies on the association between obesity and prostate cancer appear to be in conflict. A recent prospective cohort study reported that the incidence of prostate cancer was lower among obese men under the age of 60 years and among those men with a family history of prostate cancer. Similarly, a case-control study found obesity was inversely associated with prostate cancer risk in men aged 40-64 years. However, several prospective cohort studies found that obese men are more likely to die from prostate cancer than non-obese men. Finally, two recent studies found that among men with prostate cancer, obese men were more likely to have a biochemical progression after surgery. We postulate that by closely examining the comparison groups used in these studies, these findings may, in fact, be in agreement. Specifically, this paradox within the literature may result from the possibility that obesity influences the development of aggressive (i.e., higher stage, higher grade, recurrence, death) and non-aggressive disease differently. We suggest that obesity may reduce the risk of non-aggressive disease but simultaneously increase the risk of aggressive disease. Finally, additional methodological issues are discussed that investigators need to be aware of to be able to draw inferences across studies of obesity and prostate cancer outcomes.

Freedland SJ, Aronson WJ. · Brady Urological Institute, Department of Urology, Johns Hopkins School of Medicine, Baltimore, Maryland 21287-2101, USA. · Urology. · Pubmed #15780350 No free full text.

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Freedland SJ, Isaacs WB. · The Brady Urological Institute, Department of Urology, The Johns Hopkins School of Medicine, Baltimore, Maryland 21287-2101, USA. · Prostate. · Pubmed #15389726 No free full text.

Abstract: Black men in the United States have the highest incidence and mortality from prostate cancer in the world. Even after adjusting for stage at diagnosis, black men have higher mortality rates than white men. Multiple reasons have been postulated to explain these findings including access to care, attitudes about care, socioeconomic and education differences, differences in type and aggressiveness of treatment, dietary, and genetic differences. While each reason may contribute to the higher incidence or higher mortality, likely combinations of reasons will best explain all the findings. Racial differences in socioeconomic status have been well established and we review the significance of these findings in relationship to prostate cancer. Also, with recent advances in the understanding of genetic variation in the human genome, in general, and in the genes involved in pathways relevant to prostate cancer biology, in particular, a number of genes with alleles which differ in frequency between black and white men have been proposed as a genetic cause or contributor to the increased prostate cancer risk in black men. However, the clinical significance of these genetic differences is not fully known. Finally, we conclude with some thoughts as to how to integrate the findings from sociological as well as biological studies and touch upon methods to reduce the disparate burden of prostate cancer among blacks in the United States.

Freedland SJ, Pantuck AJ, Weider J, Zisman A, Belldegrun AS. · University of California, Los Angeles School of Medicine, Department of Urology, 10833 Le Conte Avenue, Room 66-118 CHS, Los Angeles, CA 90095-1738, USA. · Curr Urol Rep. · Pubmed #12084272 No free full text.

Abstract: The realization that prostate cancer is an immunogenic tumor, in conjunction with the discovery of novel methods for priming the immune system to generate an antitumor response, has resulted in several new approaches for prostate cancer immunotherapy. Based on these various approaches, several human clinical trials have begun using immune-based therapies for prostate cancer. These approaches can be divided into cytokine-based therapies, tumor-associated antigen-based therapies, tumor vaccines, and dendritic cell-based therapies. This review summarizes the latest findings from each of these approaches and gives results from the few completed human clinical trials.

Freedland SJ, Partin AW, Epstein JI, Walsh PC. · Department of Urology, The Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA. · Cancer. · Pubmed #15073852 links to  free full text

Abstract: BACKGROUND: The 1997 TNM staging system for prostate carcinoma defines a pT2a disease as a tumor histologically involving one lobe of the prostate and pT2b disease as a tumor histologically involving both prostatic lobes. Whether this distinction provides prognostic significance is unclear. The authors evaluated biochemical outcomes between men with pT2aN0 and pT2bN0 disease. METHODS: The authors identified 1606 men with organ-confined disease (pT2N0) who were treated with radical prostatectomy between 1982 and 2003 by one surgeon. Clinical characteristics were compared between men with pT2a and pT2b tumors using rank-sum analysis, and prostate-specific antigen (PSA) recurrence data were compared using log-rank analysis. The significant independent predictors of PSA recurrence were determined using a multivariate Cox proportional hazards model. RESULTS: There were no significant differences between men with pT2a and pT2b tumors at the time of surgery in terms of clinicopathologic characteristics (biopsy and pathologic Gleason score, serum PSA level, clinical stage, and age). Log-rank analysis revealed no significant differences in time to PSA recurrence between men with pT2a and pT2b tumors (P = 0.755). The 10-year PSA progression-free survival rate was 95% (confidence interval [CI], 92-97%) for men with pT2a tumors and 93% (CI, 90-95%) for men with pT2b tumors. Multivariate analysis showed that the significant predictors of PSA recurrence included serum PSA level, biopsy and pathologic Gleason score, and clinical stage. In the current cohort of men with organ-confined disease, pathologic stage (pT2a vs. pT2b) was not a significant predictor of PSA recurrence on multivariate analysis. CONCLUSIONS: There was no difference in PSA recurrence rates between men with pT2aN0 versus pT2bN0 tumors. In men with organ-confined disease, radical prostatectomy provided excellent 10-year PSA progression-free survival regardless of tumor burden (pT2a vs. pT2b). Consideration should be given to modifying the TNM staging system to eliminate substratification of pT2 tumors.

Bañez LL, Terris MK, Aronson WJ, Presti JC, Kane CJ, Amling CL, Freedland SJ. · Department of Surgery and Pathology, Duke University Medical Center, Durham, NC 27710, USA. · Cancer Epidemiol Biomarkers Prev. · Pubmed #19336564 No free full text.

Abstract: BACKGROUND: African American men with prostate cancer are at higher risk for cancer-specific death than Caucasian men. We determine whether significant delays in management contribute to this disparity. We hypothesize that in an equal-access health care system, time interval from diagnosis to treatment would not differ by race. METHODS: We identified 1,532 African American and Caucasian men who underwent radical prostatectomy (RP) from 1988 to 2007 at one of four Veterans Affairs Medical Centers that comprise the Shared Equal-Access Regional Cancer Hospital (SEARCH) database with known biopsy date. We compared time from biopsy to RP between racial groups using linear regression adjusting for demographic and clinical variables. We analyzed risk of potential clinically relevant delays by determining odds of delays >90 and >180 days. RESULTS: Median time interval from diagnosis to RP was 76 and 68 days for African Americans and Caucasian men, respectively (P = 0.004). After controlling for demographic and clinical variables, race was not associated with the time interval between diagnosis and RP (P = 0.09). Furthermore, race was not associated with increased risk of delays >90 (P = 0.45) or >180 days (P = 0.31). CONCLUSIONS: In a cohort of men undergoing RP in an equal-access setting, there was no significant difference between racial groups with regard to time interval from diagnosis to RP. Thus, equal-access includes equal timely access to the operating room. Given our previous finding of poorer outcomes among African Americans, treatment delays do not seem to explain these observations. Our findings need to be confirmed in patients electing other treatment modalities and in other practice settings.

Shah SR, Freedland SJ, Aronson WJ, Kane CJ, Presti JC, Amling CL, Terris MK. · Section of Urology, Augusta Veterans Affairs Medical Center, Augusta, Georgia, USA. · BJU Int. · Pubmed #19298411 No free full text.

Abstract: OBJECTIVE: To investigate and report the clinicopathological characteristics and outcomes after radical prostatectomy (RP) in patients with prostate cancer and previous exposure to Agent Orange (AO), particularly in relationship to race. PATIENTS AND METHODS: In 1495 veterans who had undergone RP the clinicopathological characteristics, biochemical progression rates, and prostate-specific antigen (PSA) doubling time (DT) after recurrence between AO-exposed and unexposed men were compared using logistic and linear regression and Cox proportional hazards analyses, and stratified by race. RESULTS: The 206 (14%) men with AO exposure were more likely to be black (P = 0.001), younger (P < 0.001), treated more recently (P < 0.001), have a higher body mass index (P = 0.001), have clinical stage T1 disease (P < 0.001), and have lower preoperative PSA levels (P = 0.001). After adjusting for several clinical characteristics, AO exposure was not significantly related to adverse pathological features but was significantly associated with biochemical progression risk (relative risk 1.55, 95% confidence interval 1.15-2.09, P = 0.004) and shorter PSADT (P < 0.001) after recurrence (8.2 vs 18.6 months). When stratified by race, these associations were present and similar in both races, with no significant interaction between race and AO exposure for predicting biochemical recurrence or mean adjusted PSADT (P interaction >0.20). CONCLUSIONS: Patients with AO exposure and treated with RP were more likely to be black, present with lower risk features, have an increased risk of biochemical progression, and shorter PSADT after recurrence. When stratified by race, the association between AO exposure and poor outcomes was present in both races. These findings suggest that among selected men who choose RP, AO exposure might be associated with more aggressive prostate cancer.

Gross M, Ramirez C, Luthringer D, Nepomuceno E, Vollmer R, Burchette J, Freedland SJ. · Louis Warschaw Prostate Cancer Center, Cedars-Sinai Medical Center, Los Angeles 90048, California, USA. · Prostate. · Pubmed #19107851 No free full text.

Abstract: BACKGROUND: Obesity is associated with an aggressive form of prostate cancer and with alterations in androgen and estrogen metabolism. We hypothesized that changes in components of the sex steroid receptor axis may contribute to the clinical aggressiveness of prostate cancer in obese patients. METHODS: A database was assembled containing clinical and pathological variables from 539 patients treated with radical prostatectomy at a single urban hospital between 1994 and 2002. Tissue microarrays were constructed from representative patients and expression of androgen receptor (AR), PSA, estrogen receptor alpha (ERalpha), estrogen receptor beta (ERbeta), and aromatase was examined. RESULTS: Higher BMI correlated strongly with black race, the presence of extra-capsular extension, and higher pathologic stage. Expression of AR, PSA, ERbeta and aromatase in cancerous epithelial cells did not differ according to obesity status. However, decreased expression of ERalpha and aromatase was observed in the stromal compartment surrounding non-cancerous acini in obese patients. CONCLUSION: We confirm the previously reported associations between obesity and aggressive clinical and pathologic features in our single-institution, urban teaching hospital. In comparing obese versus non-obese patients, there was no difference in expression of androgen or estrogen related proteins in cancerous epithelial cells. However, there was a down-regulation of ERalpha and aromatase in the stroma of obese patients. Our data suggest obesity may cause stromal changes in the sex steroid production and signaling pathways which may affect prostate cancer growth via intracrine/paracrine mechanisms.

Schroeck FR, Aronson WJ, Presti JC, Terris MK, Kane CJ, Amling CL, Freedland SJ. · Division of Urologic Surgery, Department of Surgery, and Duke Prostate Center, Duke University Medical Center, Durham, NC 27710, USA. · BJU Int. · Pubmed #19021608 No free full text.

Abstract: OBJECTIVE: To compare the predictive accuracy (PA) of existing models in estimating risk of biochemical recurrence (BCR) vs aggressive recurrence (BCR with a prostate-specific antigen, PSA, doubling time, DT, of <9 months). PATIENTS AND METHODS: The study included 1550 men treated with radical prostatectomy (RP) between 1988 and 2007 within the Shared Equal Access Regional Cancer Hospital database. The PA of nine different risk stratification models for estimating risk of BCR and risk of aggressive recurrence after RP was assessed using the concordance index, c. RESULTS: The 10-year risks of BCR and aggressive recurrence were 47% and 9%, respectively. Across all nine models tested, the PA was a mean (range) of 0.054 (0.024-0.074) points higher for predicting aggressive recurrence than for predicting BCR alone (c = 0.756 vs 0.702). Similar results were obtained in four sensitivity analyses: (i) defining patients with BCR but unavailable PSADT (220) as having aggressive recurrence; (ii) defining these patients as not having aggressive recurrence; (iii) defining aggressive recurrence as a PSADT of <6 months; or (iv) defining aggressive recurrence as a PSADT of <12 months. The improvement in PA was greater for preoperative than for postoperative models (0.053 vs 0.036, P = 0.03). CONCLUSION: Across nine different models the prediction of aggressive recurrence after RP was more accurate than the prediction of BCR alone. This is probably because current models mainly assess cancer biology, which correlates better with aggressive recurrence than with BCR alone. Overall, all models had relatively similar accuracy for predicting aggressive recurrence.