Prostate cancer gene 3 (PCA3) has shown promise as a molecular marker in prostate cancer detection. We assessed the correlation of the urinary PCA3 score to tumor volume determined in prostatectomy specimens as well as to other clinical and pathological features.

You have accessJournal of UrologyModerated Poster, Sunday, May 22, 2005 8:00 - 10:00 am1 Apr 2005262: Relationship of Bmi to Pathologic Features in Radical Prostatectomy Specimens in Men with Positive Surgical Margins Tiffany Sotelo, Atsushi Ochiai, Patricia Troncoso, Viju Bhadkamkar, and R. Joseph Babaian Tiffany SoteloTiffany Sotelo More articles by this author , Atsushi OchiaiAtsushi Ochiai More articles by this author , Patricia TroncosoPatricia Troncoso More articles by this author , Viju BhadkamkarViju Bhadkamkar More articles by this author , and R. Joseph BabaianR. Joseph Babaian More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34527-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "262: Relationship of Bmi to Pathologic Features in Radical Prostatectomy Specimens in Men with Positive Surgical Margins." The Journal of Urology, 173(4S), p. 72 © 2016 by American Urological AssociationFiguresReferencesRelatedDetails Volume 173Issue 4SApril 2005Page: 72 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information Tiffany Sotelo More articles by this author Atsushi Ochiai More articles by this author Patricia Troncoso More articles by this author Viju Bhadkamkar More articles by this author R. Joseph Babaian More articles by this author Expand All Advertisement PDF downloadLoading ...

Objective: Disease-associated isoforms of the prostate-specific antigen (PSA) have recently been identified. We evaluated the efficacy of using precursor isoforms of PSA (pPSA) and their ratios for the detection of prostate cancer.Methods: Serum concentrations of [-2], [-4], and [-7]pPSA, BPSA, and free PSA (fPSA) were retrospectively measured in 43 selected men. Of the 43 men, 15 had clinical T2 prostate cancer with ultrasound-estimated prostate volumes (PVs) of > 50 cm(3), 13 had clinical T2 prostate cancer with (PVs) < 25 cm(3), and 15 were prostate cancer-free with PV > 50 cm(3). We calculated sum pPSA ([-2]+[-4]+[-7]pPSA). We also compared the ratios of: free/total PSA, [-2]pPSA/fPSA, [-2]pPSA/BPSA, [-2]pPSA/(fPSA-BPSA), [-2]pPSA/(fPSA-sum pPSA), and [-2]pPSA/(fPSA-(sum pPSA+BPSA)I among these three groups.Results: The median [-2]pPSA/(fPSA-sum pPSA) ratio was significantly higher in men with prostate cancer with or without large PV compared with men with large PV without prostate cancer. Values for median [-2]pPSA/free PSA ratio were higher in men with prostate cancer with or without large PV compared with men with large PV, and without prostate cancer, but the differences were not statistically significant.Conclusions: In this preliminary study, [-2]pPSA/(fPSA-sum pPSA) ratio was not associated with prostate gland volume but was associated with prostate cancer. This ratio may be useful in the detection of prostate cancer, particularly in men with larger glands. (c) 2005 Elsevier Inc. All rights reserved.

PURPOSE:We determine the effect of clinical and pathological variables on the outcome of patients with prostate cancer of Gleason scores 8 or greater treated with radical prostatectomy alone.MATERIALS AND METHODS:Between April 1987 and October 1998, 1,199 patients underwent radical retropubic prostatectomy. We identified 188 patients assigned a Gleason score of 8 or higher in the prostatectomy specimen who did not receive any neoadjuvant or adjuvant therapy. Median followup was 60 months (range 1 to 129). Disease recurrence was defined as any detectable prostate specific antigen level 0.1 ng./ml. or greater.RESULTS:Of 188 patients 128 (68%) had no evidence of prostate cancer after a median followup of 60 months, while 60 (32%) demonstrated a detectable PSA level. There were 58 (31%) patients with disease confined to the prostate with negative surgical margins while 108 (57%) had prostate cancer confined to the surgical specimen. Positive surgical margin with extraprostatic extension was seen in 16 (9%) patients and seminal vesicle invasion was present in 40 (21%). The 5 and 7-year disease-free survival rates for the entire cohort were 71% and 55%, respectively. Patients with specimen confined disease had a significantly higher 5-year disease-free survival rate than those with nonspecimen confined disease (84% and 50%, p <0.0001). On multivariate analysis pathological status of the surgical specimen was the most significant independent predictor of disease recurrence. Age, ethnicity, clinical stage and preoperative PSA had no independent effect on disease recurrence.CONCLUSIONS:Long-term disease-free survival can be expected in those patients with high grade prostate cancer whose disease is confined to the prostate and/or the surgical specimen.

PURPOSE:It has recently been suggested that the diagnostic threshold for the prostate specific antigen (PSA) assay be lowered to enhance prostate cancer detection. A 22% incidence of prostate cancer has been reported in men with PSA between 2.5 and 4.0 ng/ml. We designed a study to confirm this observation.MATERIALS AND METHODS:Men who participated in our free early detection program and who had serum PSA between 2.5 and 4.0 ng/ml were asked to undergo prostate biopsy. Of 268 eligible men 151 (56%) agreed to participate in this free trial. All men underwent biopsy using an 11-core multisite directed biopsy scheme. All biopsy cores were color coded for location specificity and examined by 1 pathologist.RESULTS:Cancer was identified in 24.5% (37 of 151) of the men biopsied. The median age of men with cancer was 62 years (range 43 to 74). Conventional systematic sextant biopsies, which accounted for 6 of the 11 cores, detected 73.0% (27 of 37) of the cancers and the alternate site biopsies identified the remaining 10. Gleason score was 6 in 25 men, 3 + 4 in 5, 4 + 3 in 4 and 8 or greater in 3 (median Gleason score 6). There were 14 men who had 1 core positive for cancer, 9 had 2 and 14 had more than 2 (median number of positive cores 2). Of the 14 men with 1 positive core 11 had a less than 3 mm focus of cancer and 8 had only a positive alternate site biopsy. There were 11 cases of abnormal results on digital rectal examination, 5 of which were cancer, and 31 cases of abnormal results on ultrasonography, 13 of which were cancer. Median biological variability in PSA was +/-15% (range 0.4% to 440.0%).CONCLUSIONS:We found a significant incidence of cancer (24.5%, 37 of 51) in men with serum PSA between 2.5 and 4.0 ng/ml. In our study 67.6% of the detected cancers were significant based on the biopsy data. If the PSA threshold is lowered the conventional systematic sextant technique may be preferable to an extended strategy.

BACKGROUND, A variable biochemical failure rate has been reported for patients undergoing radical prostatectomy. The authors analyzed their 1987-1993 prostatectomy experience retrospectively to stratify the risk of failure in order to appropriately select patients who potentially may benefit from adjuvant therapy.METHODS. A stepwise logistic regression was used to identify variables associated with biochemical failure in 265 patients who underwent radical prostatectomy only. Prostate tumors were examined by one pathologist using 4-mm step sections. Numerous clinicopathologic variables were evaluated, and the neoplasms were subclassified into five pathologic categories based on tumor extent and margin status. Actuarial projections of biochemical failure were created using the Kaplan-Meier method.RESULTS. Pathologically, 56.2% of the tumors were organ-confined with negative margins, 12.8% had a positive surgical margin without evidence of extraprostatic extension (EPE), 24.2% had EPE (17% with negative margins and 7.2% with positive margins), and 6.8% had seminal vesicle involvement. The Gleason score was greater than or equal to 7 in 86.4% of the total population. Values for the preoperative prostate specific antigen assay were less than or equal to 4.0 ng/mL in 23.4% of the men and > 10 ng/mL in 27.7%. The overall observed biochemical failure rate in this patient group with a minimum 48 months of follow-up was 15.5%. Overall, stepwise logistic regression analysis revealed that pathologic category was the variable most strongly associated with biochemical failure and that vascular invasion was the only other examined variable associated with failure.CONCLUSIONS. The combination of pathologic category and the prostatectomy Gleason score can stratify a patient's probability of biochemical failure into three distinct groups and can identify the appropriate patients who may benefit from novel adjuvant therapeutic strategies. Cancer 2001;91:1414-22. (C) 2001 American Cancer Society.

Objectives. To explore the potential role of a neural network-derived algorithm in enhancing the specificity of prostate cancer detection compared with the determination of prostate-specific antigen (PSA) and free PSA (fPSA) while maintaining a 90% detection rate. Recent information suggests that the incidence of detectable prostate cancer is similar in men whose PSA values range from 2.5 to 4.0 ng/mL and from 4.0 to 10.0 ng/mL. If the PSA threshold triggering a prostate biopsy is lowered to 2.5 ng/mL, approximately 13% of men older than 50 would be added to the patient biopsy pool.Methods. One hundred fifty-one men were enrolled in a prospective, Institutional Review Board-approved protocol to evaluate the incidence of cancer in a population of men who participated in an early-detection program and whose PSA level was between 2.5 and 4.0 ng/mL. All the men underwent biopsy using an 11-core multisite-directed biopsy scheme, and all biopsy specimens were examined by one pathologist. All men had a second blood specimen drawn before the biopsy for a determination of serum PSA, creatinine kinase, prostatic acid phosphatase, and fPSA. A new neural network algorithm was developed with PSA, creatinine kinase, prostatic acid phosphatase, fPSA, and age as input variables to produce a single-valued prostate cancer detection index (PCD-I). This new algorithm was then prospectively tested in the 151 men. Performance parameters (including sensitivity, specificity, positive and negative predictive values, and biopsies saved) were calculated, and a comparative analysis was performed to evaluate the differences among the new algorithm, percent fPSA, PSA density, and PSA density-transition zone.Results. Cancer was histologically confirmed in 24.5% (37 of 151) of the men. The median age of the men was 62 years (range 43 to 74). At a sensitivity of 92%, the specificity for percent fPSA was 11%. The new algorithm (PCD-I) demonstrated an additional enhancement of specificity to 62% at 92% sensitivity. Clinically, the PCD-I would result in a savings of 49% (74 of 151) of all biopsies or 63.6% (71 of 114) of all unnecessary biopsies.Conclusions. A new generation algorithm, derived from a neural network (PCD-I) incorporating the parameters of age, creatinine kinase, PSA, prostatic acid phosphatase, and fPSA can significantly enhance the specificity and reduce the number of biopsies while maintaining a 92% sensitivity rate, UROLOGY 56: 1000-1006, 2000. (C) 2000, Elsevier Science Inc.

The aims of this study were to evaluate the efficacy of scintigraphy with the 99Tcm-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody Fab' fragment (IMMU4) in the diagnosis of recurrent colorectal carcinoma and to investigate its usefulness in the intraoperative surgical management of patients undergoing re-operation because of a rising serum CEA. We evaluated 24 patients prospectively who had rising serum CEA 6-19 months after initial surgery for colorectal carcinoma. Ten patients had lesions confirmed by computed tomography, ultrasound, magnetic resonance imaging, endoscopic examination or barium enema. Fourteen patients had negative findings on one or more of the above studies, but were suspected of having occult disease from their rising serum CEA. All patients were scheduled for surgery for restaging during a "second look' procedure. Planar and single photon emission tomography (SPET) imaging was performed in all patients. All scintigraphic findings were correlated with surgical and histopathological results. The overall sensitivity, specificity and accuracy were 81, 90 and 86% respectively when analysed by lesion, and 95, 60 and 88% respectively when analysed by patient. Ten of 14 (71%) patients with occult disease were correctly diagnosed as having recurrent disease. The SPET images were shown to have superior detectability (80%) compared with the planar images (35%). The surgeon judged the study to have had a neutral impact in 75% of the patients, but to have been helpful in 25%. We conclude that this antibody is potentially useful in detecting recurrent colorectal carcinoma in patients with rising serum CEA, especially when conventional imaging is negative or equivocal. It can also be helpful in altering planned surgery.

The IFNs, alpha and gamma, have been shown to enhance the tumor-associated glycoprotein (TAG-72) on adenocarcinoma cells in vitro and in mice with human breast cancer xenografts, resulting in improved targeting of monoclonal antibody CC49. To determine the effect of IFN-alpha on biodistribution and tumor uptake of 131I-labeled CC49, patients with metastatic breast cancer were randomized to either receive or not receive IFN-alpha (3 million units daily for 14 days) by s.c. injection. Three days after beginning IFN-alpha, all patients received 10-20 mCi of 131I-CC49 (specific activity, 16.7 mCi/mg) i.v. Total-body Anger camera scans, along with total-body blood and plasma pharmacokinetics, were performed. Tumor biopsies were taken in all patients before and 48 h after IFN-alpha treatment. There were no significant differences in number of metastases imaged or whole-body, blood and plasma pharmacokinetics between IFN-alpha-treated and untreated patients. Quantitative immunohistochemistry on biopsy specimens from IFN-alpha-treated patients demonstrated a significant increase in mean +/- SEM TAG-72 expression (45.7 +/- 19.4%) compared to patients that were not given IFN-alpha (1.3 +/- 0.95%; P < 0.05). Although slight increases in the percent injected dose of 131I-CC49 in tumor occurred after IFN-alpha-treatment, the changes were not significant at the P < 0.05 level. These data suggest that IFN-alpha may be useful in enhancing TAG-72 antigen expression in vivo in humans, despite modest improvement in tumor uptake of CC49, possibly because of limited tumor access or other unknown factors.

The purpose of this study was to evaluate the usefulness of SPECT bone imaging in targeting the precise location of vertebral abnormalities to ascertain whether such knowledge would help in differentiating between metastatic and benign lesions, SPECT images of the thoracolumbar spine in 50 patients were correlated with plain x-rays, CT, MRI, PET, and bone scans and 6-month clinical follow-ups, SPECT images revealed 110 lesions, 35 of which were metastases, Twenty-four of 25 lesions involving the vertebral body with extension into posterior elements were metastases, as well as 10 of 39 lesions found in the vertebral-body and 1 of 4 found in the spinous process. All lesions limited to the anterior aspect of the vertebral body (13/13), facet joints (23/23), and intervertebral disk space (6/6) were benign, In conclusion, SPECT imaging of the thoracolumbar spine is helpful in determining the precise anatomic location of vertebral abnormalities, and knowledge of the location can be used to determine whether these abnormalities in cancer patients are benign entities or metastases.

s: Fifth Conference on Radioimmunodetection and Radioimmunotherapy of Cancer: Poster Session: PDF Only

PURPOSE:We tested whether nuclear imaging with technetium 99m-labeled murine monoclonal antibody (MoAb) against carcinoembryonic antigen (CEA) IMMU-4 will detect recurrent colorectal disease in patients with a rising serum CEA level but negative abdominal and pelvic computed tomographic (CT) scan, chest radiograph, and colonoscopy, or barium enema.PATIENTS AND METHODS:Sixteen patients with completely resected, CEA-producing colorectal cancer were given 1 mg of 99mTc-labeled IMMU-4 intravenously with no toxic side effects. Planar and single-photon emission CT (SPECT) scans were acquired at 6 hours. Fifteen patients underwent an exploratory laparotomy at 24 hours. Results of the scintigraphy were correlated with surgical findings.RESULTS:Twelve of 15 patients (80%) had true-positive (TP) scans when correlated with surgery. Two of 15 (13%) had true-negative (TN) scans inasmuch as exploratory laparotomy failed to detect recurrent disease. A false-positive (FP) scan was obtained in one of 15 (7%). There were no false-negative (FN) scans. Sensitivity, specificity, accuracy, and the positive predictive value (PPV) were 100%, 67%, 93%, and 92%, respectively. Twenty-six histologically confirmed areas of malignancy were found and correlated with areas of increased activity seen on IMMU-4 scintigraphy. Twenty-one were TP; five were not detected by scintigraphy and were thus considered to be FN. There were five FP lesions and 25 TN regions. Sensitivity, specificity, accuracy, and the PPV in these 26 cancer tissues were 81%, 83%, 82%, and 81%, respectively. The median radioactivity ratio of tumorous tissue to normal tissue was 3.33, with a range of 0.89 to 17.16.CONCLUSIONS:These results suggest that 99mTc IMMU-4 scintigraphy is an important addition to the armamentarium available for diagnostic imaging and may help detect occult metastatic cancer missed by abdominal and pelvic CT in patients with rising CEA levels.

In an attempt to define the possible role of radioimmunoscintigraphy to assess noninvasively the pelvic lymph nodes, we studied 19 patients with prostate cancer. All 19 men underwent conventional radiographic imaging of the pelvis with computerized tomography or magnetic resonance imaging before bilateral pelvic lymph node dissection. In addition, radioimmunological scanning with 111indium-labeled monoclonal antibody CYT-356 was performed. Pathologically 8 of the 19 patients had histological confirmation of metastatic nodal disease ranging from 1 to 15mm. The monoclonal scan was positive at a site corresponding to the histologically confirmed nodal foci in 4 of the 8 patients. Since each hemipelvis could be independently assessed for pathological disease and imaging status, we report site-specific analysis of the monoclonal antibody scan in 38 hemipelves. The overall accuracy was 76% with a sensitivity and specificity of 44% and 86%, respectively. The negative predictive value was 83% and the positive predictive value was 50%. The administration of a single dose of CYT-356 antibody is safe, feasible and capable of detecting soft tissue nodal disease. A negative scan enables the physician to predict noninvasively a low probability of nodal disease for individuals at high risk. The detection threshold of this antibody scan appears to be disease foci 5mm. or greater.

Podoloff, D. A.; Delpassand, E. S.; Quadrl, S. M.; Bhadkamkar, V. A.; South, M. S.; Bellinger, P. M.; Vriesendorp, H. M. Author Information

Delpassand, E. S. M.D.; Bhadkamkar, V. A. M.Sc., M.S.; Haynie, T. P. M.D.; Garcia, Jose R. M.D.; Podoloff, Donald A. M.D., UT M.D. Author Information

PURPOSE:The purpose of this phase I trial was to determine the toxicity and maximum-tolerated dose (MTD) of murine monoclonal antibody (Mab) 14G2a (anti-GD2) in cancer patients.PATIENTS AND METHODS:Following tracer doses of iodine-131-labeled 14G2a to determine tumor uptake, 18 patients with refractory melanoma, neuroblastoma, or osteosarcoma received unlabeled 14G2a at total concentrations of 50, 100, and 200 mg/m2 administered as daily 24-hour infusions for 5 days.RESULTS:The overall sensitivity of external immunoscintigraphy was 64 of 74 known metastases (86%). Toxicity from prolonged infusion of 14G2a consisted of severe generalized pain, hyponatremia, fever, rash, paresthesias, weakness, and chronic refractory postural hypotension (two patients). Toxicity was less severe in pediatric patients. The MTD of Mab was 100 mg/m2. Sixteen of 18 patients developed human antimouse antibodies (HAMA) to 14G2a. Terminal-phase half-life (T1/2) of unlabeled Mab was 6.6 +/- 1.8 hours for patients receiving 50 mg/m2 and 39.5 +/- 13.3 hours at the 100-mg/m2 level. Tumor biopsies from six melanoma patients were positive for GD2 antigen, but only two of six had trace amounts of 14G2a present. Three mixed responses (two melanoma, one osteosarcoma) and two partial responses (PRs; neuroblastoma) were observed.CONCLUSION:Mab 14G2a has modest antitumor activity at the expense of significant toxicity. Dose-limiting neurologic sequelae may significantly limit phase II studies other than in pediatric patients with neuroblastoma.