Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database.

BACKGROUND: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology. METHODS: We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively. RESULTS: In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining ≥ 2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI): 1.03-2.64, P=0.04) while weight loss ≥ 2.5 kg was not associated with BCR (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41). CONCLUSIONS: As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain ≥ 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain ≥ 2.5 kg may promote prostate cancer progression.

The influence of hepatic function on prostate cancer outcomes after radical prostatectomy.

Prostate growth is dependent on circulating androgens, which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2 and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum > or =7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; P=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade, but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing RP. The effect of moderate-to-severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.

The effect of race on the discriminatory accuracy of models to predict biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital and Duke Prostate Center databases.

To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015-0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (-0.036; range -0.078 to -0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3-4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race.

Preoperative predictors of blood loss at the time of radical prostatectomy: results from the SEARCH database.

The literature contains conflicting data on preoperative predictors of estimated blood loss (EBL) at radical retropubic prostatectomy (RRP). We sought to examine preoperative predictors of EBL at the time of RRP among patients from the SEARCH database to lend clarity to this issue. A total of 1154 patients were identified in the SEARCH database who underwent RRP between 1988 and 2008 and had EBL data available. We examined multiple preoperative factors for their ability to predict EBL using multivariate linear regression analysis. Median EBL was 900 ml (s.d. 1032). The 25th and 75th percentile for EBL were 600 and 1500 ml, respectively. EBL increased significantly with increasing body mass index (BMI) and increasing prostate size and decreased with more recent year of RRP (all P<0.001). The mean-adjusted EBL in normal-weight men (BMI<25 kg/m(2)) was 807 ml compared to 1067 ml among severely obese men (BM I>or=35 kg/m(2)). Predicted EBL for men with the smallest prostates (<20 g) was 721 ml, compared to 1326 ml for men with prostates >or=100 g. Finally, statistically significant differences between centers were observed, with mean-adjusted EBL ranging from 844 to 1094 ml. Both BMI and prostate size are predictors of increased EBL. Prostate size is of particular note, as a nearly twofold increased EBL was seen from the smallest (<20 g) to the largest prostates (>or=100 g). Over time, average EBL significantly decreased. Finally, significant differences in EBL were observed between centers. Patients with multiple risk factors should be forewarned they are at increased risk for higher EBL, which may translate into a greater need for blood transfusion.

Impact of nerve sparing on surgical margins and biochemical recurrence: results from the SEARCH database.

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.

Is there a difference in outcome after radical prostatectomy between patients with biopsy Gleason sums 4, 5, and 6? Results from the SEARCH database.

PURPOSE: Fewer patients newly diagnosed with prostate cancer today have biopsy Gleason sums <6 compared to several years ago. Several tables and nomograms for predicting disease recurrence after definitive therapy provide little or no discrimination between biopsy Gleason sums 4, 5, and 6. We sought to examine the significance of biopsy Gleason sum for predicting biochemical failure following radical prostatectomy (RP) for men with biopsy Gleason sums of 4, 5, and 6. MATERIALS AND METHODS: We examined data from 988 men treated with RP between 1988 and 2002 who had biopsy Gleason sums of 4-6. Clinical and pathological variables as well as outcome information were compared between men with biopsy Gleason sums of 4-6. The log-rank and Cox proportional hazards analysis were used to determine whether biopsy Gleason sum provided unique prognostic information for men with low biopsy Gleason sums undergoing RP. RESULTS: There was statistically significant, but overall weak correlation between biopsy Gleason sum and Gleason sum of the RP specimen (Spearman's r=0.277, P<0.001). As biopsy Gleason sum increased from 4 to 5 to 6, there was a steady rise (HR=1.31 for each one point increase in Gleason sum, Cox's model) in the risk of PSA failure (P=0.025, log-rank). On multivariate analysis comparing biopsy Gleason sum, preoperative PSA, clinical stage, year of surgery, percent of biopsy cores positive, and age for their ability to predict time to biochemical recurrence, only PSA (HR 2.09, CI 1.56-2.80, P<0.001) and biopsy Gleason sum (HR 1.33, CI 1.05-1.70, P=0.019) were significant independent predictors of PSA failure. CONCLUSIONS: Despite weak correlation between biopsy and pathologic Gleason sum among men with biopsy Gleason sum 4-6 tumors, grade was a significant independent predictor of PSA failure following RP. In the range of 4-6, biopsy Gleason sum acted as a continuous variable for predicting PSA failure. The routine use of Gleason sums 4 and 5 to grade prostate needle biopsy specimens should not be abandoned.

p53 immunoreactivity correlates with Ki-67 and bcl-2 expression in renal cell carcinoma.

This study assessed the relation of proliferation, inhibition of apoptosis, and the p53 tumor suppressor protein expression in clear renal cell carcinoma (RCC). Archival pathological specimens from 43 patients treated for RCC were obtained. Median follow-up for the patients was 52 months (range 2.5 months to 178 months). Immunostaining of paraffin tissue sections was carried out for four different markers: a) Ki-67, a marker for cellular proliferation; b) p53/DO7, c) p53/pAb240, antibodies for the p53 protein; and d) bcl-2, a marker for inhibition of apoptosis (programmed cell death). One thousand cells were counted per slide at 400x magnification. Staining of >/=10% of cells was considered positive and <10% negative. Fisher exact contingency tables were used for correlation between markers, tumor grade and stage. A significant correlation was found between Ki-67 and p53 immunoreactivity samples, P=0.0001. Interestingly, a significant association was found if Ki-67 and bcl-2 scores were combined and correlated with p53, P=0.009. Results showed no correlation between any of the immunohistochemical markers and grade or stage. In addition, Kaplan-Meier survival curves demonstrated no significant difference between patients' tumors that was scored immunoreactive negative vs. positive for Ki-67, p53, or bcl-2. This study indicates that p53 expression correlates with proliferation, and inhibition of programmed cell death in RCC.

Comparative genomic hybridization.

Comparative genomic hybridization (CGH) allows a genome-wide survey of the relative copy number of tumor DNA in a single hybridization. The tumor-cell DNA (Test DNA) is hybridized together with a sex-matched normal DNA (Reference DNA) onto normal metaphase spreads. Test DNA and Reference DNA are labeled with fluorochrome-conjugated reagents of different color, thereby allowing the detection of genetic imbalance in the abnormal cells.

Management of a positive surgical margin after radical prostatectomy: decision analysis.

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.

Contemporary approach to the classification of renal epithelial tumors.

Our understanding of the morphologic and genetic features of renal epithelial neoplasia has brought about profound changes in the classification of these tumors. It is clear that they represent a heterogeneous group of tumors with distinct histopathologic, genetic, and clinical features ranging from benign to high-grade malignant. "Granular" and "sarcomatoid" carcinomas are not distinct entities, since tumors with granular or spindle cell features may be seen in many tumor-types. Using conventional pathologic tools such as hematoxylin and eosin staining, histochemistry, immunohistochemistry, and electron microscopy, we are able to properly classify the majority of these tumors. Nevertheless, approximately 6% to 7% of cases are impossible to classify in this fashion, thus requiring molecular genetic studies for proper characterization.

Late presentation of ureteral injury after laparoscopic surgery.

OBJECTIVE: To describe clinical presentation, etiology, and treatment of ureteral injuries recognized late in women who had gynecologic laparoscopies. METHODS: We reviewed the charts of 12 women who had delayed recognition of ureteral injuries between January 1991 and December 1998. RESULTS: Patients presented with fever, hematuria, flank pain, or peritonitis between 3 and 33 days postoperatively. The mechanism of ureteral injuries was electrocoagulation in seven women, laser ablation in one, and stapler ligation in four. The sites of injury were near the inferior margin of the sacroiliac joint on excretory urogram in eight women and near the ureterovesical junction in four. Three women initially treated with internal ureteral stents were subsequently treated with ureteroneocystostomy because of progression of urinary ascites in two and a delayed ureteral stricture in one. In nine patients, attempts at ureteral stenting were unsuccessful and immediate ureteral reconstruction was done. Outcomes were good in all cases. CONCLUSION: Delayed recognition of ureteral injury after gynecologic laparoscopy was associated with serious complications, and initial treatment with ureteral stenting was not useful. We advocate early open repair for those injuries.

Prostate cancer: assessment of risk using digital rectal examination, tumor grade, prostate-specific antigen, and systematic biopsy.

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.

Potential role of nephrectomy in the treatment of metastatic renal cell carcinoma: a retrospective analysis.

OBJECTIVES: To examine the outcomes of patients with newly diagnosed metastatic renal cell carcinoma (RCC) who underwent initial nephrectomy as a component of therapy, because the role of nephrectomy in the treatment of patients with metastatic RCC is uncertain. METHODS: A retrospective review of 63 patients who underwent radical nephrectomy with or without additional surgical procedures in the setting of metastatic RCC was performed. Pretreatment characteristics and the type of surgery were examined as predictors of outcome, and the type of systemic therapy received (if any) and overall survival were determined. RESULTS: The median patient age was 59 years (range 39 to 79). Thirty-two patients had a single metastatic site, with the most common sites being the lung (n = 33), lymphatics (n = 32), and bone (n = 19). Seventeen patients (27%) also underwent vena cavotomy during surgery. Two patients died perioperatively. Thirty-nine (62%) patients underwent systemic therapy after surgery, and 6 patients (9.5%) were rendered free of disease and elected not to receive systemic treatment. The median survival was 17.8 months. CONCLUSIONS: Primary renal surgery may be beneficial for selected patients with metastatic RCC, and most patients will be able to receive postoperative systemic therapy.

The optimal systematic prostate biopsy scheme should include 8 rather than 6 biopsies: results of a prospective clinical trial.

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.

The role of the urologist in adjuvant chemotherapy trials for prostate cancer.

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.

Number of positive systematic sextant biopsies predicts surgical margin status at radical prostatectomy.

OBJECTIVES: To determine whether the number of positive sextant biopsies contributes to the prediction of positive surgical margins, as the value of systematic prostate biopsies in predicting margin status at radical prostatectomy is unclear. METHODS: Consecutive patients (n = 108) who underwent radical retropubic prostatectomy and systematic sextant biopsies were retrospectively evaluated. Serum prostate-specific antigen, digital rectal examination, primary Gleason grade, Gleason score, and the number and location of positive sextant biopsies were recorded for each patient. Radical prostatectomy specimens were evaluated by step-section techniques at 3 to 5-mm intervals. Univariate comparisons for each of these variables was performed between the positive and negative margin groups using the Mann-Whitney U test or chi-square analysis. Logistic regression analysis was performed for these variables. RESULTS: Twenty-two (20.4%) of 108 patients had a positive surgical margin because of extension of the tumor through the capsule. Patients with three or more positive biopsies were at higher risk of having a positive surgical margin (P = 0.009). Patients with bilaterally positive biopsies at either the base or midprostate were more likely to have a positive surgical margin. The risk of a positive surgical margin was not significantly determined by the primary Gleason grade, Gleason score, or prostate-specific antigen. Multivariate logistic regression models were created that consistently demonstrate that the number of positive biopsies was the best predictor of margin status. CONCLUSIONS: This study demonstrated that the number of positive sextant biopsies contributes to the prediction of margin status at radical prostatectomy.

Diffuse retroperitoneal amyloidosis due to renal cell carcinoma.

The case of a 61-year-old man with haematuria, in whom CT demonstrated a solid renal mass and extensive retroperitoneal infiltration, is presented. This combination of CT findings resulted in significant diagnostic uncertainty. Pathological analysis demonstrated renal cell carcinoma, with secondary amyloidosis in the retroperitoneum. Amyloidosis secondary to renal cell carcinoma has not been previously described as a cause of retroperitoneal infiltration.

The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience.

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.

Positive fraction of systematic biopsies predicts risk of relapse after radical prostatectomy.

OBJECTIVES: To determine whether the positive fraction of systematic sextant biopsies contributes to the prediction of serologic relapse after radical prostatectomy. METHODS: A retrospective review of patients who underwent transrectal ultrasound-guided systematic sextant biopsy and radical prostatectomy was performed. No patients received neoadjuvant or adjuvant therapy. The relationship between the positive fraction of systematic biopsies and risk of prostate-specific antigen recurrence was assessed with Kaplan-Meier and multivariate analyses. RESULTS: Patients with three or fewer positive sextant biopsies were at a significantly lower risk of relapse after radical prostatectomy than patients with four or more positive biopsies. Tumor grade and systematic biopsy results were the most powerful predictors of serologic relapse. CONCLUSIONS: The positive fraction of systematic biopsies contributes to the prediction of risk of relapse after radical prostatectomy.

Prospective evaluation of lateral biopsies of the peripheral zone for prostate cancer detection.

PURPOSE: We evaluate the usefulness of adding 4 lateral biopsies of the peripheral zone to the routine sextant biopsy regimen for prostate cancer. MATERIALS AND METHODS: A total of 273 consecutive patients referred for abnormal digital rectal examination and/or prostate specific antigen 4 ng./ml. or greater underwent transrectal ultrasound and systematic biopsy. Lateral biopsies of the peripheral zone taken just medial to the lateral border of the prostate were added to the routine lesion directed and systematic sextant biopsy regimen. Comparisons between positive and negative biopsy groups as well as among various biopsy schemes were performed. RESULTS: Of the patients 44% had cancer on biopsy (121 of 273). While routine sextant biopsies detected 82% of cancers, 77% (17 of 22) of missed cancers were detected on lateral biopsies. Overall, lateral biopsies detected 70% of cancers, and tended to be positive in patients with small prostates and high grade tumors. A significant correlation was found between hypoechoic lesions on transrectal ultrasound and positive lateral biopsies (Fisher's exact test p = 0.0005). Cancer was found in 74 of 147 patients with lesions on transrectal ultrasound (50%). Routine sextant biopsies detected 76% of cancers (56 of 74 patients) while lateral biopsies detected 80% (59). Of these patients 15 (20%) had positive lateral and negative sextant biopsies. Routine sextant biopsies detected 91% of cancers in 121 patients without lesions on ultrasound (43 of 47). CONCLUSIONS: The addition of lateral peripheral zone biopsies increases the sensitivity for cancer detection while nearly eliminating the need for lesion directed biopsies.