Prostatic Neoplasms: Presti JC

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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Presti JC. · Stanford Cancer Center, Stanford, CA 94305-5826, USA. · Nat Clin Pract Urol. · Pubmed #17823604 No free full text.

Abstract: Early detection is critical to good management of prostate cancer patients. Markers for detection, such as prostate specific antigen (PSA), and prostate biopsy are paramount for establishing an efficient diagnosis. Patients having an initial biopsy should undergo an extended biopsy scheme incorporating at least 10-12 cores, while in those undergoing a repeat biopsy particular attention should be addressed to the anterior apex. Saturation biopsies should be considered for patients with several prior negative biopsies. The chance of finding cancer on repeat biopsies has diminished in patients harboring high-grade prostatic intraepithelial neoplasia but not in those with atypical small acinar proliferation. This article reviews the history of prostate biopsy strategies with particular attention paid towards the development of extended biopsy schemes. Furthermore, a strategy is recommended for initial and repeat biopsy patients.

Presti JC. · Division of Urologic Oncology, Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5826, USA. · Curr Opin Urol. · Pubmed #15586023 No free full text.

Abstract: PURPOSE OF REVIEW: This review provides an update on research into the association between obesity and prostate cancer. RECENT FINDINGS: The US Health Professional Study reported an inverse relationship between risk for prostate cancer and obesity in men under the age of 60 or in those with a positive family history for prostate cancer. Others found no association between obesity and risk for the disease. Regarding detection, obesity does not impact upon measurement of prostate specific antigen as a method of detecting prostate cancer; however, in a referral population there was an inverse association between detection rate and obesity. In three radical prostatectomy series, obesity was associated with worse pathological features and higher biochemical relapse rates. Possible mechanisms for the association between obesity and prostate cancer include the impact on serum testosterone, leptin, insulin-like growth factor I, and interleukin-6 levels. SUMMARY: A growing body of evidence suggests that obesity may impact upon risk, detection and outcome with regard to prostate cancer.

Grossfeld GD, Tigrani VS, Nudell D, Roach M, Weinberg VK, Presti JC, Small EJ, Carroll PR. · Department of Urology, University of California-San Francisco, San Francisco, California, USA. · J Urol. · Pubmed #10840431 No free full text.

Abstract: PURPOSE: We created and tested a decision analysis model to help determine the preferred management of a positive surgical margin(s) after radical prostatectomy. MATERIALS AND METHODS: We constructed a decision tree modeling surveillance versus immediate prophylactic adjuvant radiation in patients with a positive surgical margin(s) after radical prostatectomy. Literature and institution based estimates were determined for certain factors, including the probability of undetectable prostate specific antigen (PSA) in patients followed expectantly postoperatively and those treated with immediate adjuvant radiotherapy, complications of radiotherapy after prostatectomy and probability of undetectable PSA in those treated with therapeutic radiation for detectable PSA postoperatively. A panel of experts assigned utilities to the various outcomes. Sensitivity analysis was performed to determine threshold values required to change the model outcome. RESULTS: Using average probability estimates from a literature review the decision model recommended initial surveillance. Sensitivity analysis demonstrated that the model depended on the probability of disease recurrence in men followed expectantly after surgery as well as the efficacy of therapeutic radiation. We tested the decision model again for patient groups based on tumor grade, pathological stage, preoperative PSA and number of positive margins. The model recommended initial radiation for patients with low to intermediate grade disease, no evidence of seminal vesicle invasion and multiple positive margins. CONCLUSIONS: The results of our decision analysis imply that immediate radiation may be appropriate for patients with a positive surgical margin(s) and a high likelihood of recurrent local rather than distant disease. This model may be useful to physicians and patients who use individual probability estimates and utility values to determine the preferred course of management after surgery.

Presti JC. · Department of Urology, University of California San Francisco, USA. · Radiol Clin North Am. · Pubmed #10664666 No free full text.

Abstract: Refinement in the local staging and risk assessment for prostate cancer patients utilizing clinical parameters is ongoing. DRE, tumor grade, and PSA provide some useful information for risk assessment in individual patients. More recent studies using percent free PSA levels and systematic biopsy results have added additional staging information and may play a more significant role in the future in risk assessment. This information should supplement additional imaging tests in the management of these patients.

Presti JC. · Department of Urology, University of California, San Francisco, USA. · Urology. · Pubmed #10606284 No free full text.

Abstract: The urologist is ideally positioned to identify patients at high risk for relapse after radical prostatectomy. Several models have been proposed to help the urologist identify which patients are at risk and who should be considered for adjuvant therapy after radical prostatectomy. The appropriate initial trial design considered for this group of patients should be a randomized two-arm trial, without androgen deprivation, to assess more quickly the efficacy of selected agents.

King CR, Brooks JD, Gill H, Pawlicki T, Cotrutz C, Presti JC. · Department of Radiation Oncology, Division of Urologic Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Int J Radiat Oncol Biol Phys. · Pubmed #18755555 No free full text.

Abstract: PURPOSE: The radiobiology of prostate cancer favors a hypofractionated dose regimen. We report results of a prospective Phase II clinical trial of stereotactic body radiotherapy (SBRT) for localized prostate cancer. METHODS AND MATERIALS: Forty-one low-risk prostate cancer patients with 6 months' minimum follow-up received 36.25 Gy in five fractions of 7.25 Gy with image-guided SBRT alone using the CyberKnife. The early (<3 months) and late (>6 months) urinary and rectal toxicities were assessed using validated quality of life questionnaires (International Prostate Symptom Score, Expanded Prostate Cancer Index Composite) and the Radiation Therapy Oncology Group (RTOG) toxicity criteria. Patterns of prostate-specific antigen (PSA) response are analyzed. RESULTS: The median follow-up was 33 months. There were no RTOG Grade 4 acute or late rectal/urinary complications. There were 2 patients with RTOG Grade 3 late urinary toxicity and none with RTOG Grade 3 rectal complications. A reduced rate of severe rectal toxicities was observed with every-other-day vs. 5 consecutive days treatment regimen (0% vs. 38%, p = 0.0035). A benign PSA bounce (median, 0.4 ng/mL) was observed in 12 patients (29%) occurring at 18 months (median) after treatment. At last follow-up, no patient has had a PSA failure regardless of biochemical failure definition. Of 32 patients with 12 months minimum follow-up, 25 patients (78%) achieved a PSA nadir </=0.4 ng/mL. A PSA decline to progressively lower nadirs up to 3 years after treatment was observed. CONCLUSIONS: The early and late toxicity profile and PSA response for prostate SBRT are highly encouraging. Continued accrual and follow-up will be necessary to confirm durable biochemical control rates and low toxicity profiles.

Presti JC, Chang JJ, Bhargava V, Shinohara K. · Department of Urology, University of California School of Medicine, San Francisco, USA. · J Urol. · Pubmed #10604337 No free full text.

Abstract: PURPOSE: We define the optimal systematic biopsy regimen to detect carcinoma of the prostate. MATERIALS AND METHODS: A total of 483 consecutive patients referred for an abnormal digital rectal examination and/or prostate specific antigen (PSA) 4.0 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone at the base and mid gland were added to the routine sextant biopsy regimen for a total of 10 systematic biopsies of the peripheral zone. Patients with a prostate greater than 50 cc also underwent systematic sextant transition zone biopsy in the mid lobar parasagittal plane. Detection rates of the various regions were assessed. Various biopsy schemes were then created and cancer detection rates were compared using McNemar's test. RESULTS: Of the patients 42% (202 of 483) had cancer on biopsy. Traditional sextant biopsies missed 20%, while a sextant regimen incorporating lateral peripheral zone biopsies of the mid gland and base along with the apex missed 11% of the cancers. The combination of sextant and lateral peripheral zone biopsies (10-biopsy scheme) detected 194 cancers (96%). The 8 missed cancers were detected by lesion directed (5) or transition zone (3) biopsies. Eliminating the mid lobar base biopsies from the systematic 10-biopsy peripheral zone regimen resulting in an 8-biopsy peripheral zone regimen decreased detection from 96% to 95%. CONCLUSIONS: The 6 systematic biopsies of the peripheral zone are inadequate and a minimum of 8, including the apex, mid lobar mid gland, lateral mid gland and lateral base, should routinely be performed.

Koppie TM, Shinohara K, Grossfeld GD, Presti JC, Carroll PR. · Department of Urology and University of California, San Francisco/Mt. Zion Cancer Center, USA. · J Urol. · Pubmed #10411051 No free full text.

Abstract: PURPOSE: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months. RESULTS: Serial PSA data was available after 181 initial and repeat procedures. Nadir PSA was undetectable in 88 patients (49%), between 0.1 and 0.4 ng./ml. in 39 (21%) and 0.5 ng./ml. or greater in 54 (30%) following cryosurgery. After 78 of these procedures (43%) serum PSA reached a nadir of less than 0.5 ng./ml. and failed to increase greater than 0.2 ng./ml. on at least 2 occasions. Prostate biopsy was performed following 167 procedures and was positive after 64 (38%). CONCLUSIONS: Cryosurgery was associated with favorable serum PSA characteristics in 49% of patients 3 years after treatment. Undetectable PSA nadir and pretreatment PSA 10 ng./ml. or less were associated with a favorable outcome, with a biochemical disease-free survival of 77% and 61% 3 years after treatment, respectively.

Presti JC. · Department of Urology, Stanford University School of Medicine, Stanford, CA 94305, USA. · Urol Oncol. · Pubmed #19414120 No free full text.

Abstract: Patients who have a persistently elevated or a rising PSA level following a prior negative prostate biopsy can be a stressful situation for both the urologist and the patient. This will be a brief review of the indications and techniques in patients undergoing a repeat biopsy. In patients with a prior negative biopsy, assessing the adequacy of the initial biopsy is important. F/T PSA is currently the most useful marker in predicting cancer on repeat biopsy although newer markers, such as PCA3, are promising. Repeat biopsies should include a minimum of 14 cores, the 12 cores recommended for an initial biopsy and 2 additional cores obtained form the right and left anterior apex. In patients for whom repeat biopsies fail to identify cancer, yet the clinical suspicion remains high, consideration for a saturation biopsy approach seems warranted.

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.

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.

Teeter AE, Bañez LL, Presti JC, Aronson WJ, Terris MK, Kane CJ, Amling CL, Freedland SJ, Anonymous00461. · Division of Urologic Surgery and Duke Prostate Center, Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA. · J Urol. · Pubmed #18801519 No free full text.

Abstract: PURPOSE: Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis in men with prostate cancer. We determined which demographic and clinicopathological variables were predictive of a short prostate specific antigen doubling time in a cohort of men with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Data on 856 men from the Shared Equal Access Regional Cancer Hospital database who underwent radical prostatectomy for node negative prostate cancer between 1988 and 2003 were included in the analysis. We used logistic regression analysis to determine the independent factors associated with a short prostate specific antigen doubling time of less than 9 months vs a longer doubling time of 9 months or greater, or no recurrence. The variables analyzed were patient age, race, logarithmically transformed preoperative prostate specific antigen, body mass index, year of surgery, pathological Gleason sum, extraprostatic extension, surgical margin status and seminal vesicle invasion. RESULTS: On multivariate analysis higher preoperative prostate specific antigen (OR 2.20, 95% CI 1.52-3.19, p <0.001), pathological Gleason sum 8-10 (OR 4.70, 95% CI 2.11-10.43, p <0.001) and 7 (OR 2.11, 95% CI 1.09-4.08, p = 0.026), tumors with extraprostatic extension and/or positive surgical margins (OR 2.08, 95% CI 1.48-3.91, p = 0.023), and seminal vesicle invasion (OR 3.26, 95% CI 1.48-7.21, p = 0.003) were independent predictors of a short prostate specific antigen doubling time. Based on these risk factors we developed a table to estimate the risk of recurrence with a prostate specific antigen doubling time of less than 9 months. CONCLUSIONS: The factors that are invariably used to predict overall biochemical recurrence following radical prostatectomy, including high prostate specific antigen, high grade and adverse pathological findings, also predict aggressive recurrence.

Turley RS, Terris MK, Kane CJ, Aronson WJ, Presti JC, Amling CL, Freedland SJ, Anonymous00080. · Division of Urological Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, NC 27710, USA. · BJU Int. · Pubmed #18778348 No free full text.

Abstract: OBJECTIVE: To test the hypothesis that the association between prostate size and risk of Gleason grade upgrading varies as a function of sampling. PATIENTS AND METHODS: We examined the association between pathological prostate weight, prostate biopsy scheme and Gleason upgrading (Gleason > or =7 at radical prostatectomy, RP) among 646 men with biopsy Gleason 2-6 disease treated with RP between 1995 and 2007 within the Shared Equal Access Regional Cancer Hospital Database using logistic regression. In all, 204 and 442 men had a sextant (six or seven cores) or extended-core biopsy (eight or more cores), respectively. Analyses were adjusted for centre, age, surgery, preoperative prostate-specific antigen level, clinical stage, body mass index, race, and percentage of cores positive for cancer. RESULTS: In all, 281 men (44%) were upgraded; a smaller prostate was positively associated with the risk of upgrading in men who had an extended-core biopsy (P < 0.001), but not among men who had a sextant biopsy (P = 0.22). The interaction between biopsy scheme and prostate size was significant (P interaction = 0.01). CONCLUSIONS: These data support the hypothesis that the risk of upgrading is a function of two opposing contributions: (i) a more aggressive phenotype in smaller prostates and thus increased risk of upgrading; and (ii) more thorough sampling in smaller prostates and thus decreased risk of upgrading. When sampled more thoroughly, the phenotype association dominates and smaller prostates are linked with an increased risk of upgrading. In less thoroughly sampled prostates, these opposing factors nullify, resulting in no association between prostate size and risk of upgrading. These findings help to explain previously published disparate results of the importance of prostate size as a predictor of Gleason upgrading.

Elliott CS, Shinghal R, Presti JC. · Department of Urology, Stanford University School of Medicine, California 94305-5118, USA. · J Urol. · Pubmed #18707710 No free full text.

Abstract: PURPOSE: The incidence of prostate cancer is known to vary as a function of race. To date few studies have evaluated the performance of the prostate specific antigen test and its indexes in unique racial populations. We examined the performance of prostate specific antigen, prostate specific antigen density and transition zone density in racial groups undergoing an extended prostate biopsy scheme. MATERIALS AND METHODS: A retrospective review was performed of prospectively collected data on 1,115 white, 288 black and 161 Asian/Pacific Islander men referred for prostate needle biopsy. All participants had not undergone previous biopsy. ROC curves stratified by race were ascertained for prostate specific antigen, prostate specific antigen density and transition zone density for detecting cancer and high grade cancer (Gleason 3 + 4 or greater). RESULTS: Across all races prostate specific antigen density outperformed prostate specific antigen for detecting any prostate cancer and high grade cancer. Prostate specific antigen and prostate specific antigen density performed best for diagnosing high grade cancer and diagnosing cancer in men with an abnormal digital rectal examination. When comparing differing races, prostate specific antigen density performed the best in Asian/Pacific Islander men for high grade cancer detection. The performance of transition zone density was inferior to that of prostate specific antigen density. CONCLUSIONS: Racial variations exist in the performance of prostate specific antigen and prostate specific antigen density. In men of Asian/Pacific Islander descent prostate specific antigen and prostate specific antigen density perform better than in white men, especially for diagnosing clinically significant, high grade prostate cancer. In general prostate specific antigen and prostate specific antigen density perform equally well in white and black populations.

Anonymous00339, Jayachandran J, Aronson WJ, Terris MK, Presti JC, Amling CL, Kane CJ, Freedland SJ. · Urology Section, Veterans Affairs Medical Center, Duke University School of Medicine, Durham, NC 27710, USA. · BJU Int. · Pubmed #18691176 No free full text.

Abstract: OBJECTIVES: To determine if there is predilection for any specific anatomical location of positive surgical margins (PSMs) after radical prostatectomy (RP) for prostate cancer in obese men, as previous studies found that obesity was associated with an increased risk of PSMs. PATIENTS AND METHODS: We analysed retrospectively 1434 men treated with RP between 1989 and 2007 within the Shared Equal Access Regional Cancer Hospital database. The association between increased body mass index (BMI) and overall and site-specific PSMs was assessed using multivariate logistic regression. RESULTS: After adjusting for several preoperative clinical and pathological characteristics, a higher BMI was associated with an increased risk of PSMs both overall and at all specific anatomical locations (all P <or= 0.007). For mildly obese men, this risk was very similar across all anatomical sites (44-78% increased risk relative to men of normal weight). When BMI was coded as a continuous variable, the odds ratio for the risk of overall PSMs or at any specific locations was nearly identical at 1.05-1.06. Among men with a BMI of >or=35 kg/m2, there was more variation, with the highest excess risk of PSMs at the bladder neck and apex. CONCLUSIONS: Obesity was associated with an increased risk of overall PSMs and at all anatomical locations. Although the excess risk of PSMs was similar across all anatomical locations, there was a suggestion of a higher risk of apical margins among the most obese men, which if validated, further supports the importance of the apical dissection in all men and suggests added difficulty in obese patients.

Freedland SJ, Sun L, Kane CJ, Presti JC, Terris MK, Amling CL, Moul JW, Aronson WJ. · Urology Section, Department of Surgery, Veterans Affairs Medical Center, Duke University Medical Center, Durham, NC 27710, USA. · BJU Int. · Pubmed #18691175 No free full text.

Abstract: OBJECTIVE: To indirectly test the hypothesis that prostate-specific antigen (PSA)-based screening is biased against obese men due to haemodilution of PSA, and thus results in delayed diagnosis and poorer outcome beyond the biological link between obesity and aggressive prostate cancer. PATIENTS AND METHODS: We sought to examine the association between body mass index (BMI) and the outcome of radical prostatectomy (RP) separately for men with PSA-detected cancers (cT1c) or with abnormal digital rectal examination (DRE) findings (cT2/T3), and stratified by year of treatment, using two large databases. We conducted a retrospective cohort study of 1375 and 2014 men treated by RP between 1988 and 2007 using the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. We evaluated the association between BMI and adverse pathological features and biochemical progression, using logistic regression and Cox proportional hazards models, adjusting for several clinical characteristics, respectively. Data were examined as a whole and as stratified by clinical stage (cT1c vs cT2/T3) and year of surgery (>or=2000 vs <2000). RESULTS: In both cohorts a higher BMI was associated with high-grade disease (P <or= 0.02) and positive surgical margins (P < 0.001) and these results did not vary by clinical stage. A higher BMI was significantly associated with biochemical progression (P <or= 0.03) in both cohorts. When stratified by clinical stage, obesity was significantly related to progression in both cohorts among men with T1c cancers (P <or= 0.004) but not in men with cT2/T3 cancers (P > 0.3). Among men with T1c disease, the association between BMI and biochemical progression was limited to men treated in 2000 or later (P <or= 0.002) and was not apparent in men treated before 2000 (P > 0.4). CONCLUSIONS: Obese men with PSA-detected cancers and treated with RP since 2000 were at significantly greater risk of biochemical progression, while obese men treated before 2000 or diagnosed with an abnormal DRE were not at significantly greater risk of progression. These findings support the hypothesis that current PSA-based screening is less effective at finding cancers in obese men, leading to more aggressive tumours at diagnosis. Lowering the PSA threshold for biopsy among obese men might help to improve outcomes among this high-risk group.

Nelles JL, Freedland SJ, Presti JC, Terris MK, Aronson WJ, Amling CL, Kane CJ. · Department of Urology, San Francisco School of Medicine, University of California, San Francisco, CA, USA. · Prostate Cancer Prostatic Dis. · Pubmed #18626507 No free full text.

Abstract: The effects of nerve sparing on the risk of positive surgical margins (PSMs) and biochemical recurrence after radical prostatectomy (RP) remain controversial. We examined data from 1018 men treated by RP between 1988 and 2006 at five centers in the Shared Equal Access Regional Cancer Hospital database. Neither bilateral nor unilateral nerve-sparing techniques were associated with a higher risk of PSM; on multivariate analysis of individual sides, the risk of PSM on either side was not increased by nerve sparing on either side. The risk for biochemical recurrence was not affected by bilateral or unilateral nerve sparing. When used on appropriately selected patients, nerve sparing does not increase the probability of PSM or biochemical recurrence after RP.

Hamilton RJ, Aronson WJ, Terris MK, Kane CJ, Presti JC, Amling CL, Freedland SJ. · Division of Urologic Surgery, Department of Surgery, Duke University School of Medicine, Durham, North Carolina 27710, USA. · J Urol. · Pubmed #18343434 No free full text.

Abstract: PURPOSE: Prostate specific antigen doubling time following biochemical recurrence after radical prostatectomy is a powerful predictor of prostate cancer specific and overall death. To calculate prostate specific antigen doubling time requires multiple prostate specific antigen determinations that are unaltered by secondary therapy and separated by sufficient time. Physicians and patients may be unwilling to wait before starting secondary therapy, especially for high risk recurrences. Hence, those with calculable prostate specific antigen doubling time may represent a select lower risk group relative to all men with biochemical recurrence. MATERIALS AND METHODS: We compared clinical and pathological features between patients with and without calculable prostate specific antigen doubling time. We assessed time trends in the proportion with calculable prostate specific antigen doubling time in 535 patients with biochemical recurrence after radical prostatectomy at 5 Veterans Affairs medical centers comprising the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 1988 and 2003. RESULTS: Prostate specific antigen doubling time was not calculable in 187 patients (35%) due to secondary therapy in 155 (83%). With time the proportion of patients with calculable prostate specific antigen doubling time decreased significantly (p <0.001). Adverse pathological features, more rapid time to recurrence, higher body mass index and differing surgical centers were associated with not having a calculable prostate specific antigen doubling time. Of all men with recurrence in the most recent year of analysis the adjusted probability of having a calculable prostate specific antigen doubling time was only 43%, that is 61% in patients with favorable pathological results but only 30% in those with seminal vesicle invasion. CONCLUSIONS: Those with calculable prostate specific antigen doubling time represented a select, lower risk cohort and the proportion of patients with calculable prostate specific antigen doubling time decreased with time. This highlights the need for alternative markers in men with recurrent prostate cancer because one of our best current markers, prostate specific antigen doubling time, is only available in a limited number of patients.

Jayachandran J, Bañez LL, Levy DE, Aronson WJ, Terris MK, Presti JC, Amling CL, Kane CJ, Freedland SJ, Anonymous00047. · Division of Urologic Surgery, Department of Surgery, Duke University School of Medicine, Durham, North Carolina 27710, USA. · J Urol. · Pubmed #18343426 No free full text.

Abstract: PURPOSE: In men with extracapsular disease or positive surgical margins after radical prostatectomy immediate adjuvant therapy decreases the risk of biochemical recurrence at the cost of increased toxicity. We further stratified these men into a low risk group in which watchful waiting after surgery may be preferred and a high risk cohort in which adjuvant therapy may be preferred. MATERIALS AND METHODS: We performed a retrospective analysis of the records of 902 men treated with radical prostatectomy in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database between 1988 and 2007 with positive surgical margins and/or extracapsular disease without seminal vesicle invasion or lymph node metastasis. The significant independent predictors of biochemical recurrence were determined using a multivariate Cox proportional hazards model. Based on the recurrence risk generated from the multivariate Cox proportional hazards regression model we generated tables to estimate the risk of recurrence-free survival 1, 3 and 5 years after surgery. RESULTS: At a median of 3 years of followup 346 patients (39%) had biochemical recurrence. On multivariate analysis the significant predictors of biochemical recurrence were age more than 60 years, prostate specific antigen more than 10 ng/ml, Gleason score 4 + 3 and 8-10, 2 or more sites of positive surgical margins and prostate specimen weight 30 gm or less. As determined by the concordance index, the overall predictive accuracy of the model was 0.67, while it was 0.60 for the postoperative Kattan nomogram in this patient population. CONCLUSIONS: We have developed a simple instrument that, once validated, may aid in the postoperative decision making process for men at intermediate risk for recurrence after prostatectomy.

Elliott CS, Shinghal R, Presti JC. · Department of Urology, Stanford University School of Medicine, Stanford, California, USA. · J Urol. · Pubmed #18343425 No free full text.

Abstract: PURPOSE: Prostate specific antigen, prostate specific antigen density and transition zone density have been previously identified as prostate cancer detection tools. Recent studies suggest that prostate specific antigen may be increasingly accurate for detecting clinically significant high grade prostate cancer (Gleason grade 7 or greater). We defined the performance of these measures in a referral based population undergoing an extended prostate biopsy scheme. MATERIALS AND METHODS: We retrospectively reviewed prospectively collected data on 1,708 men referred for prostate needle biopsy. All participants were men who had not undergone biopsy in the past. From these data ROC curves were constructed for prostate specific antigen, prostate specific antigen density and transition zone density for the presence of cancer, high grade (Gleason 3 + 4 or greater) and high volume (50% or greater of cores positive) disease. RESULTS: Prostate specific antigen density had a statistically higher AUC than prostate specific antigen for detecting all prostate cancers (0.737 vs 0.633, p <0.001) as well as high grade (0.766 vs 0.673, p <0.001) and high volume (0.843 vs 0.755, p <0.001) disease. Additionally, prostate specific antigen and prostate specific antigen density performed better for detecting high grade and high volume disease compared to overall prostate cancer detection. The performance of transition zone density was similar to that of prostate specific antigen density. CONCLUSIONS: Prostate specific antigen and prostate specific antigen density show improved performance characteristics for detecting clinically significant high grade and high volume prostate cancer in referral populations undergoing extended scheme prostate needle biopsy. Prostate specific antigen density shows better performance characteristics than prostate specific antigen. No advantage was seen when using transition zone density over prostate specific antigen density.

Heath EI, Kattan MW, Powell IJ, Sakr W, Brand TC, Rybicki BA, Thompson IM, Aronson WJ, Terris MK, Kane CJ, Presti JC, Amling CL, Freedland SJ. · Barbara Ann Karmanos Cancer Institute, Department of Hematology and Oncology, Wayne State University, 4100 John R, 4 HWCRC, Detroit, MI 48201, USA. · Urology. · Pubmed #18242385 No free full text.

Abstract: OBJECTIVES: To test the accuracy of the 2001 Partin Tables in African American men who underwent radical prostatectomy at multiple centers throughout the United States. METHODS: We compiled a large multiethnic cohort of men (n = 3748) treated with radical prostatectomy at multiple sites, including all of the sites of the Department of Veterans Affairs-based Shared Equal Access Regional Cancer Hospital (SEARCH) database (n = 1524), Wayne State University (n = 1305), the University of Texas Health Science Center (n = 522), and the Henry Ford Hospital (n = 397). We evaluated the accuracy of the 2001 Partin Tables using area under the receiver operator characteristic curve (AUC) separately among African American and white men. RESULTS: African American men (n = 1188, 32%), despite being more likely to have clinical Stage T1c disease (56% versus 47%, chi-square P <0.001), had higher preoperative PSA values (9.1 versus 7.7 ng/mL, rank-sum P <0.001) and were more likely to have higher-grade disease on diagnostic biopsy (chi-square P = 0.005). Despite these differences in baseline clinical characteristics, the 2001 Partin Tables performed equally well in both racial groups. Specifically, there were no differences in the AUC for African American and white men for predicting organ-confined disease (AUC 0.73 versus 0.72; P = 0.56), extraprostatic extension (AUC 0.62 versus 0.62; P = 0.99), or seminal vesicle invasion (AUC 0.77 versus 0.79; P = 0.53). CONCLUSIONS: These data lend further support to the idea that although baseline differences between the races existed that may underlie an overall more aggressive disease among African American men, for the individual patient, race is not valuable for prognostication.

Turley RS, Hamilton RJ, Terris MK, Kane CJ, Aronson WJ, Presti JC, Amling CL, Freedland SJ, Anonymous00450. · Division of Urological Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina, USA. · J Urol. · Pubmed #18076952 No free full text.

Abstract: PURPOSE: Needle biopsy Gleason scores are often upgraded after pathological examination of the prostate following radical prostatectomy. It has been suggested that larger prostates would be associated with a greater risk of upgrading since a smaller percentage of the gland is sampled and, thus, the highest grade disease would more likely be missed, assuming an equal number of cores is taken from similar locations. We examined the likelihood of clinically relevant upgrading after radical prostatectomy as a function of transrectal ultrasound volume. MATERIALS AND METHODS: We examined the association between transrectal ultrasound volume and upgrading (higher Gleason score category in the radical prostatectomy specimen than in the biopsy) in 586 men treated with radical prostatectomy between 1995 and 2006 in the SEARCH database who underwent at least a sextant biopsy using multivariate logistic regression. Transrectal ultrasound volume was categorized as 20 or less (in 71), 21 to 40 (in 334), 41 to 60 (in 123) and greater than 60 cm(3) (in 58). Gleason score was examined as a categorical variable of 2-6, 3 + 4 and 4 + 3 or greater. RESULTS: Overall 138 cases (24%) were upgraded, 80 (14%) were downgraded, and 368 (62%) had identical biopsy and pathological Gleason sum groups. Larger transrectal ultrasound volume was significantly associated with decreased likelihood of upgrading (p trend <0.001). For transrectal ultrasound volumes greater than 60, 41 to 60, 21 to 40 and 20 cm(3) or less, the estimated multivariate adjusted probability of upgrading was 12.6%, 27.5%, 36.4% and 45.5% for Gleason 2-6 tumors, and 6.1%, 8.5%, 18.9% and 20.9% for Gleason 3 + 4 tumors, respectively. CONCLUSIONS: Larger transrectal ultrasound volumes were at decreased risk for clinically significant upgrading after radical prostatectomy. This fact should be kept in mind when deciding on treatment decisions for men with apparently low grade prostate cancer on biopsy.

Bañez LL, Hamilton RJ, Partin AW, Vollmer RT, Sun L, Rodriguez C, Wang Y, Terris MK, Aronson WJ, Presti JC, Kane CJ, Amling CL, Moul JW, Freedland SJ. · Division of Urologic Surgery and the Duke Prostate Center, and Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. · JAMA. · Pubmed #18029831 links to  free full text

Abstract: CONTEXT: Recent studies have suggested that obese men have lower serum prostate-specific antigen (PSA) concentrations than nonobese men. Because men with higher body mass index (BMI) have greater circulating plasma volumes, lower PSA concentrations among obese men may be due to hemodilution. OBJECTIVE: To determine the association between hemodilution and PSA concentration in obese men with prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: Retrospective study of men who underwent radical prostatectomy for prostate adenocarcinoma from 1988 to 2006, using data from the databases of the Shared Equal Access Regional Cancer Hospital (n = 1373), Duke Prostate Center (n = 1974), and Johns Hopkins Hospital (n = 10 287). Multivariate linear regression models adjusting for clinicopathological characteristics were used to analyze the main outcome measures. MAIN OUTCOME MEASURES: Associations between BMI and mean adjusted PSA concentrations, mean plasma volume, and mean adjusted PSA mass (total circulating PSA protein, calculated as PSA concentration multiplied by plasma volume), assessed by determining P values for trend. RESULTS: After controlling for clinicopathological characteristics, higher BMI was significantly associated with higher plasma volume (P < .001 for trend) and lower PSA concentrations (P < or = .02 for trend) in all cohorts. In 2 of the 3 cohorts, PSA mass did not change significantly with increasing BMI. In the third cohort, higher BMI was associated with increased PSA mass (P < .001 for trend), but only between BMI category less than 25 and the other categories. CONCLUSIONS: In men undergoing radical prostatectomy, higher BMI was associated with higher plasma volume; hemodilution may therefore be responsible for the lower serum PSA concentrations among obese men with prostate cancer. Prospective studies are needed to evaluate this association in screened populations.