Prostate cancer: detection, staging, and treatment of localized disease.
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Biomarkers, Tumor↗
Biomedical subjects
A W Partin
Publications and source records attributed to A W Partin.
Incidental non-Hodgkin's lymphoma in patients with localized prostate cancer.
OBJECTIVES: To determine the outcome of patients with clinically organ-confined prostate cancer undergoing radical retropubic prostatectomy for cure and incidentally discovered concurrent low-grade non-Hodgkin's lymphoma at time of surgery. METHODS: From September 1986 to September 1997, 4319 patients underwent radical retropubic prostatectomy at our institution. The records of 10 patients incidentally diagnosed to have low-grade non-Hodgkin's lymphoma at the time of radical prostatectomy were retrospectively reviewed. RESULTS: Of 4319 patients requiring radical prostatectomy, 10 (0.2%) were found to have low-grade non-Hodgkin's lymphoma. All 10 men had an uneventful postoperative course. Two patients subsequently developed progression of lymphoma, one of whom required treatment. One patient died of sepsis associated with his lymphoma and 1 patient died of an unrelated malignancy (lung cancer), both 7 years following surgery. Two patients developed biochemical prostate-specific antigen recurrence. The remainder of men were free of prostate cancer recurrence and experienced no progression of lymphoma at an average of 45 months (range 12 to 142). CONCLUSIONS: Patients with organ-confined prostate cancer, who are candidates for radical prostatectomy, experience long-term prostate cancer-free survival in the face of incidentally diagnosed low-grade lymphoma. Because the management of most incidentally discovered low-grade lymphomas is expectant, patients discovered at surgery to have this clinical entity should not be denied radical prostatectomy.
Aged↗
Nuclear morphometry adds significant prognostic information to stage and grade for renal cell carcinoma.
OBJECTIVES: Identification of patients with a high probability of recurrence after nephrectomy for renal cell carcinoma (RCC) is required for adjuvant studies of new therapies. Nuclear morphometry predicts prognosis for prostate, bladder, and Wilms' tumors and in RCC according to previous small pilot studies. METHODS: To validate this finding, we studied an additional 101 patients who underwent nephrectomy for Stage pT1 to pT3 RCC at our institution from 1977 to 1993 for whom data regarding recurrence or disease-free survival of greater than 60 months were available. Patient records and pathology specimens were reviewed. Of the 101 patients, 66 (65%) did not experience recurrence with greater than 60 months of follow-up, and 35 (35%) had RCC recurrence with a median time to recurrence of 17 months. Nuclear shape descriptors were tested as predictors of disease recurrence after accounting for stage and grade in proportional hazards regression models. RESULTS: Range of ellipticity (hazards ratio 3.39, P = 0.014) was confirmed to be a significant predictor of recurrence. A prognostic model using stage, grade, and range of ellipticity identified three distinct groups: low, moderate, and high recurrence risk groups, with recurrence rates of 4%, 37%, and 63%, respectively, at 5 years of follow-up. Morphometry significantly (P = 0.018) improved prognostication on the basis of stage and grade alone in this multivariate model. CONCLUSIONS: Nuclear morphometry is valid and accurate in predicting relapse in early-stage RCC. The model can select patients with RCC for adjuvant therapies.
Carcinoma, Renal Cell↗
Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with nonpalpable disease.
OBJECTIVES: To evaluate the relation between age, prostate-specific antigen (PSA) level, and the probability of detecting curable prostate cancer. METHODS: A consecutive surgical series of radical prostatectomies was performed in 492 men with nonpalpable (Stage T1c) disease, who formed the study cohort (mean age 58 years). The cohort was systematically classified into three age groups ([1] 40 to 50 years [n = 69]; [2] 51 to 60 years [n = 227]; [3] 61 to 73 years [n = 196]) and five pretreatment PSA groups ([1] 2.5 to 4.0 ng/mL [n = 36]; [2] 4.1 to 6.0 ng/mL [n = 100]; [3] 6.1 to 8.0 ng/mL [n = 122]; [4] 8.1 to 10.0 ng/mL [n = 76]; [5] greater than 10.0 ng/mL [n = 135]). The percent probability of curable cancer was determined by logistic regression analysis. Curable cancer was defined as organ-confined tumor or a tumor with capsular penetration of low grade (Gleason score less than 7), with negative margins and no involvement of seminal vesicles or lymph nodes. RESULTS: A comparison within age groups and within PSA groups revealed that the probability of curable cancer was more closely associated with age than PSA level. Although the probability of curable cancer was closely related to PSA level across a wide range of PSA values (0.4 to 52 ng/mL), there was only minimal difference (2% to 4%) in the probability of curable cancer within the range of PSA values from 2.5 to 6.0 ng/mL for all ages. CONCLUSIONS: Age is a strong predictor of the probability of curable cancer. Thus, early detection efforts in younger men are more likely to lead to a decrease in prostate cancer mortality. These data suggest that the use of PSA thresholds below 4.0 ng/mL as an indicator of prostate cancer is unlikely to improve the probability of detecting curable cancer.
Adult↗
Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial.
OBJECTIVES: Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS: In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS: Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.
Adrenergic alpha-Antagonists↗
Ablation of renal tumors in a rabbit model with interstitial saline-augmented radiofrequency energy: preliminary report of a new technology.
OBJECTIVES: To evaluate the efficacy of interstitial saline radiofrequency energy for reproducibly ablating nonmalignant (control) and malignant (the VX-2 tumor) renal tissue in a rabbit model, and to determine the ability of conventional gray-scale and power sonography to image the tumor and ablative process in real time before, during, and after treatment. METHODS: The VX-2 tumor was implanted beneath the renal capsule in 18 rabbit kidneys. Twelve days after implantation, 50 W of 500-kHz radiofrequency energy was delivered into the surgically externalized renal tumor and contralateral control kidney for 30 or 45-second treatment intervals using an interstitial saline-augmented radiofrequency probe (the virtual electrode). Localization of the tumor and response to treatment were imaged with gray-scale and power Doppler ultrasonography. The effect of radiofrequency and extent of the destructive process on benign and malignant renal tissue were evaluated histologically. RESULTS: Mean tumor size was 1.3 x 0.7 cm. Both 30 and 45-second treatment intervals provided marked tissue/tumor ablation. Gross anatomic and histologic analysis showed time-dependent ablated lesions averaging 1.4+/-0.3 x 1.0+/-0.3 cm (30-second treatment) and 1.8+/-0.4 x 1.5+/-0.3 cm (45-second treatment), with clear demarcation of the surrounding parenchyma. Conventional gray-scale sonography allowed visualization of the ablative process, and power Doppler ultrasound demonstrated changes in the vascular pattern of the tumor both before and after ablation. No immediate treatment-related complications were observed. CONCLUSIONS: These preliminary studies in a rabbit model demonstrate the feasibility of using the interstitial saline-augmented electrode to ablate small renal tumors and the ability to simultaneously visualize the ablative process using real-time ultrasonography. This technology may have the potential to treat small renal tumors in a minimally invasive manner in the clinical setting.
Animals↗
Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings.
OBJECTIVES: Prostate cancer is rarely diagnosed in men younger than 40 years of age. It is thought, although not documented, that these tumors behave particularly aggressively. METHODS: We studied 87 men younger than 40 years old who underwent prostate needle biopsy and were from three populations: (a) 71 cases (63 benign, 7 cancer) from Dianon Systems; (b) 9 needle biopsies with cancer sent to one of us (J.I.E.) in consultation; and (c) 7 men with cancer who came to Johns Hopkins for consultation. RESULTS: The median age of men with a benign biopsy was 35 years (mean 33.9, range 22 to 39); the median age of men with cancer was 38 years (mean 35.9, range 22 to 39) (P = 0.004). The most common indications for biopsy were abnormal digital rectal examination (DRE) (n = 61); elevated prostate-specific antigen (PSA) (n = 14), and inflammatory symptoms (n = 12). Other reasons cited included hematuria, abnormal ultrasound, pain, ejaculatory problems, obstructive symptoms, and family history of prostate cancer. The median PSA was 2.6 ng/mL (mean 4.8, range 0.3 to 66) for all men, 1.2 ng/mL (mean 3.4, range 0.3 to 19.9) for benign cases, and 4.4 ng/mL (mean 8.7, range 2.1 to 66) for cancer (P = 0.0004). Abnormal DRE was not predictive of cancer. Of the 55 patients whose family history was known, 40 men had no family history of prostate cancer, and of those, only 6 (15%) had cancer. Of the 1 5 patients with a family history of cancer, 6 (40%) were found to have cancer on biopsy (P = 0.05). Of the 23 patients with cancer, 3 were lost to follow-up, 1 was treated with hormones, and 3 chose watchful waiting. The remaining 16 patients underwent radical prostatectomy and had diverse pathologic findings. Tumor volume ranged from 0.01 to 6.35 cc. Pathologic stage was pT2 in 9 cases and pT3 in 7 cases (2 with positive pelvic lymph nodes). In 14 men, serum PSA values were available: of 4 men with PSA greater than 10 ng/mL, all had Stage pT3, and of 10 men with PSA less than 10 ng/mL, 3 had Stage pT3. CONCLUSIONS: Young men who are candidates for radical prostatectomy have potentially curable disease, particularly if PSA at the time of diagnosis is less than 10 ng/mL.
Adenocarcinoma↗
Use of percentage of free prostate-specific antigen to identify men at high risk of prostate cancer when PSA levels are 2.51 to 4 ng/mL and digital rectal examination is not suspicious for prostate cancer: an alternative model.
OBJECTIVES: Currently, many clinicians do not recommend prostate biopsy for men with digital rectal examination (DRE) results that are not suspicious for cancer and prostate-specific antigen (PSA) values between 2.51 and 4 ng/mL. We propose a new model for the detection of prostate cancer using the percentage of free PSA (%FPSA) in the limited range of PSA values between 2.51 and 4 ng/mL that maximizes clinical specificity (ie, minimizes false-positive results). This model identifies higher risk patients in this relatively low-risk population. METHODS: Three hundred sixty-eight archived serum samples from men evaluated and treated at two academic institutions were reviewed. All men had a histologic diagnosis, findings not suspicious for cancer on DRE, and PSA levels between 2.51 and 4 ng/mL. Samples were tested in Hybritech's Tandem-R PSA and Tandem-R free PSA (FPSA) assays in the same laboratory at each institution. RESULTS: Various models for cancer detection using %FPSA when PSA is 2.51 to 4 ng/mL and DRE is not suspicious for cancer are proposed. These models recommend biopsy for only 10% to 36% of the men in this population and would identify as many as 30% to 54% of the detectable cancers. There is evidence that the cancers that would be detected are the most aggressive cancers in this population. CONCLUSIONS: Our models identified men with a higher risk of prostate cancer in a relatively low-risk population that currently does not routinely undergo biopsy. This may allow for a more cost-effective way to increase cancer detection when PSA values are between 2.51 and 4 ng/mL and DRE is not suspicious for cancer. This model has the potential to detect a greater number of clinically important and potentially curable cancers than would be detected with current practice.
Aged↗
Use of human glandular kallikrein 2 for the detection of prostate cancer: preliminary analysis.
OBJECTIVES: Human glandular kallikrein 2 (hK2) and prostate-specific antigen (PSA) are members of a multigene family of serine proteases that share approximately 80% sequence homology. Both are expressed in the prostate epithelium, are under androgen regulation, are present in serum and seminal fluid, and can form complexes with endogenous protease inhibitors (eg, alpha2-macroglobulin and alpha1-antichymotrypsin). Differences in immunohistochemistry and substrate specificity suggest hK2 may provide unique information for early detection and characterization of prostate cancer. METHODS: Nine hundred thirty-seven archived serum samples from men treated at two academic institutions were studied. All men underwent biopsy, had a histologically confirmed diagnosis of cancer or noncancer, and a total PSA level greater than 2 ng/mL. Samples were tested in Hybritech's Tandem-R PSA and Tandem-R free PSA (fPSA) assays and a research prototype assay for total hK2 (thK2). RESULTS: The thK2/fPSA ratio provided additional specificity for cancer detection over PSA and the percentage of fPSA (%fPSA). A model for cancer detection using %fPSA and the thK2/fPSA ratio when PSA is 2 to 4 ng/mL is proposed that would identify as many as 40% of the cancers and would require biopsy in only 16.5% of the men in this PSA range. CONCLUSIONS: In this study, %fPSA and thK2/fPSA provided unique information for prostate cancer detection and increased the specificity of cancer detection.
Aged↗
Nuclear shape and nuclear matrix protein composition in prostate and seminal vesicles.
OBJECTIVES: The nucleus controls cell function and behavior. The nuclear matrix determines internal nuclear changes. Two-dimensional gel electrophoresis is the reference standard for the analysis of nuclear matrix protein (NMP) composition. Differences in NMP composition should therefore be reflected by changes in nuclear shape. We investigated the differences in NMP composition and nuclear morphometry of the prostate and seminal vesicles. Both tissues are androgen-dependent sex accessory organs with completely different biologic behavior. METHODS: High-resolution two-dimensional gel electrophoresis and silver staining were used to evaluate NMP composition from histologically normal prostate and seminal vesicle epithelial cells. Nuclear morphometry, performed using a computer-assisted image analysis system, described the distribution, variability, and extremes of nuclear shape. RESULTS: NMP composition analysis demonstrated that both tissues have a similar NMP composition, and tissue-specific NMPs that were consistently present in all specimens of each tissue could not be demonstrated. Nuclear morphometry showed a significantly greater heterogeneity in nuclear shape in the seminal vesicles than in the prostate. CONCLUSIONS: The striking similarity of the NMP composition demonstrates the close biologic relationship between prostate and seminal vesicle tissue. The similar NMP composition does not correlate with the marked alterations in nuclear shape and structure between these tissues. Therefore, nuclear morphometry may depict differences in the functional state of a similar set of NMPs, shown by two-dimensional gel electrophoresis, which may be responsible for the different biologic behavior of these tissues.
Antigens, Nuclear↗
Immunoscintigraphy with indium-111-capromab pendetide: evaluation before definitive therapy in patients with prostate cancer.
OBJECTIVES: No standard noninvasive diagnostic test reliably differentiates patients with organ-confined prostate cancer from those with lymph node metastases. The ability of a radiolabeled monoclonal antibody, indium-111 (111ln)-capromab pendetide, to identify sites of metastatic disease in patients at moderate to high risk of nodal involvement was investigated. METHODS: The study prospectively evaluated 160 patients with prostate cancer scheduled to undergo pelvic lymph node dissection (PLND) before or during definitive treatment. All were at relatively high risk of nodal involvement by virtue of significantly elevated baseline prostate-specific antigen (PSA) values, Gleason scores, and/or locally advanced clinical stages of disease. The histologic findings of the PLNDs were compared with the results of immunoscintigraphy, computed tomography, and magnetic resonance imaging. RESULTS: Among the 152 evaluable patientS studied with 111In-capromab pendetide before PLND, the sensitivity of immunoscintigraphy for lymph node detection was 62% and the specificity was 72%; the positive predictive value was 62% and the negative predictive value was 72%. In comparison, the sensitivity of computed tomography and magnetic resonance imaging was 4% and 15%, respectively, and the specificity was 100% for both procedures on the basis of a large number of negative interpretations. Logistic regression analysis revealed that immunoscintigraphy with 111In-capromab pendetide provided strong, independent evidence of the presence of lymph node metastases. Furthermore, the analysis indicated that certain combinations of PSA, Gleason score, and 111In-capromab pendetide were particularly effective at predicting the risk of nodal involvement. CONCLUSIONS: Immunoscintigraphy with 111In-capromab pendetide outperformed standard diagnostic imaging techniques in the detection of prostate cancer lymph node metastases and provided independent prognostic information that complemented PSA, Gleason score, and clinical stage.
Adenocarcinoma↗
Genetically engineered neural networks for predicting prostate cancer progression after radical prostatectomy.
OBJECTIVES: To use pathologic, morphometric, DNA ploidy, and clinical data to develop and test a genetically engineered neural network (GENN) for the prediction of biochemical (prostate-specific antigen [PSA]) progression after radical prostatectomy in a select group of men with clinically localized prostate cancer. METHODS: Two hundred fourteen men who underwent anatomic radical retropubic prostatectomy for clinically localized prostate cancer were selected on the basis of adequate follow-up, pathologic criteria indicating an intermediate risk of progression, and availability of archival tissue. The median age was 58.9 years (range 40 to 87). Men with Gleason score 5 to 7 and clinical Stage T1b-T2c tumors were included. Follow-up was a median of 9.5 years. Three GENNs were developed using pathologic findings (Gleason score, extraprostatic extension, surgical margin status), age, quantitative nuclear grade (QNG), and DNA ploidy. These networks were developed using three randomly selected training (n = 136) and testing (n = 35) sets. Different variable subsets were compared for the ability to maximize prediction of progression. Both standard logistic regression and Cox regression analyses were used concurrently to calculate progression risk. RESULTS: Biochemical (PSA) progression occurred in 84 men (40%), with a median time to progression of 48 months (range 1 to 168). GENN models were trained using inputs consisting of (a) pathologic features and patient age; (b) QNG and DNA ploidy; and (c) all variables combined. These GENN models achieved an average accuracy of 74.4%, 63.1 %, and 73.5%, respectively, for the prediction of progression in the training sets. In the testing sets, the three GENN models had an accuracy of 74.3%, 80.0%, and 78.1%, respectively. CONCLUSIONS: The GENN models developed show promise in predicting progression in select groups of men after radical prostatectomy. Neural networks using QNG and DNA ploidy as input variables performed as well as networks using Gleason score and staging information. All GENN models were superior to logistic regression modeling and to Cox regression analysis in prediction of PSA progression. The development of models using improved input variables and imaging systems in larger, well-characterized patient groups with long-term follow-up is ongoing.
Adult↗
Cell turnover in human seminal vesicles and the prostate: an immunohistochemical study.
The human prostate and seminal vesicles are both androgen-dependent sex accessory organs. Their growth behavior, response to hormone manipulation, susceptibility to benign and malignant processes and sex accessory functions, however, differ greatly. The growth behavior of most tissues correlates well with the cell turnover rate of that tissue. Therefore, we compared the cell turnover of normal human prostate and seminal vesicles. Immunohistochemical expression of MIB-1 (proliferation), bcl-2 and transforming growth factor (TGF beta) were examined in 20 different samples taken from histologically normal human prostatic and seminal vesicle tissue. For the quantification of apoptosis, the TUNEL technique was used. The apoptosis rates in normal prostatic tissue (0.73+/-0.60) were significantly greater (P=0.003) than those seen in seminal vesicles (0.02+/-0.01). The proliferation rates also differed significantly (P=0.002) between these tissues (prostate: 0.77+/-0.78; seminal vesicles: 0.02+/-0.02). Eighty percent of the prostate tissue stained for bcl-2, whereas only 55% of the seminal vesicle tissue showed staining for bcl-2. All seminal vesicles and 75% of the prostate samples stained for TGF beta. For both androgen-dependent tissues, apoptotic rates closely equaled proliferation rates. The cell turnover, however, was much higher in the prostate than in the seminal vesicles. TGF beta seems to be more important for the regulation of cell turnover in the seminal vesicles than bcl-2. These differences in the proliferative behavior may explain why disturbances of apoptotic regulation lead to a more extensive net cell gain in prostatic tissue compared to the seminal vesicles. This might help explain the vastly different incidence of benign and malignant tumors in these organs.
Journal Article↗
Artificial neural networks in urology: Update 2000.
Artificial neural networks (ANNs) are widely available and have been demonstrated to be superior to standard empirical methods of detecting, staging and monitoring prostate cancer. These algorithms have been statistically validated in diverse, well-characterized patient groups and are now being evaluated for clinical use worldwide. New variables based on demographic data, tissue and serum markers show promise for improving our ability to predict disease extent and outcome and may be integrated in future ANN models. This review focuses on recently developed neural networks for detecting, staging and monitoring prostate cancer.
Journal Article↗
Generation of PSA-ACT-specific monoclonal antibodies and their application in a sandwich immunoassay.
The prostate-specific antigen (PSA) immunoassay is an important tool for the detection and monitoring of prostate cancer. PSA exists in serum mainly as complexes with serine protease inhibitors including alpha1 antichymotrypsin (ACT) and alpha2 macroglobulin (MG). PSA-MG complex is not detected by the existing PSA immunoassays since MG (720 kDa) sequesters PSA and masks the antibody binding sites. Existing immunoassays for quantitation of total serum PSA measure PSA-ACT (CPSA) and free PSA (FPSA), which comprise the major and minor components of total PSA, respectively. Monoclonal antibodies (MAb) specific for CPSA alone were generated using a unique immunogen prepared by blocking the major antigenic determinants on FPSA and ACT. The blocked immunogen greatly enhanced the frequency of hybridomas reactive against the CPSA complex. CPSA prototype immunoassays were established using anti-CPSA (PX1G359) or anti-ACT (AC1A212) MAb as tracer MAb and anti-PSA (PSA399) MAb as capture MAb. The complex-selective MAbs demonstrated minimal cross-reactivity with Cathepsin-G (CG) ACT (CG-ACT), ACT or FPSA. CG-ACT complex interfered with the accuracy of initial prototype assays specific for CPSA measurement and caused over-recovery (1 to 3 ng/mL, with 40 to 180 ng/mL range of CG-ACT in serum) of apparent CPSA values. Addition of 0.4% NP-40 and 0.1% 0.088 micron microparticles in clinical specimens eliminated this interference. Specimens from 39 prostate cancer (PCa) patients and 44 benign prostatic hyperplasia (BPH) patients were analyzed with the PX1G359 CPSA assay. In this study, the area under the curve (AUC) values for ROC analysis of total PSA (CPSA+FPSA), FPSA to total PSA ratio (f/t), and FPSA to CPSA ratio (f/c) were 0.357, 0.634, and 0.624, respectively. In a second study using AC1A212 CPSA assay, where specimens from 16 PCa patients and 48 BPH patients were tested, the AUC values for total PSA, f/t and f/c ratios were 0.62, 0.785, and 0.732, respectively. Using the CPSA assay with minimal interference our studies are consistent with previous CPSA data showing that the f/t PSA ratio remains superior to the f/c PSA ratio in differentiating PCa and BPH diseases. Complex PSA by itself or as ratio with free or total PSA does not provide any advantage over the established method of FPSA to total PSA ratio.
Animals↗
Influence of sextant prostate needle biopsy or surgery on the detection and harvest of intact circulating prostate cancer cells.
PURPOSE: The feasibility of harvesting intact, circulating prostate cancer cells from the blood of men with advanced prostate cancer has previously been demonstrated. We studied the influence of sextant prostate needle biopsy and radical prostatectomy on harvesting intact circulating prostate cancer cells. MATERIALS AND METHODS: Via standard venipuncture 20 c.c. blood were obtained preoperatively, and 30 minutes and 3 days postoperatively from 23 men with clinically localized prostate cancer undergoing surgery. Similarly, blood was obtained before and after routine prostate biopsy from 13 men for an elevated prostate specific antigen level and/or abnormal digital rectal examination. The blood cells were removed via density centrifugation and magnetic cell sorting. The remaining prostate epithelial cells were characterized by indirect fluorescent immunocytochemical staining and fluorescent in situ hybridization using deoxyribonucleic acid probes. RESULTS: Sextant biopsy of the prostate induced circulating cells in 3 of 13 men (23%), only 1 of whom demonstrated cells with aneuploidy (Gleason score 3+4 = 7). Circulating cells were detected preoperatively, 30 minutes or 3 days postoperatively in 35% of radical prostatectomy cases. Of the patients 13% had detectable circulating cells 30 minutes postoperatively only and 9% had cells harvested on postoperative day 3. Persistence of circulating prostate cancer cells was noted in 13% of men on postoperative day 3. Serum prostate specific antigen level and pathological stage did not appear to be related to harvested cell number. CONCLUSIONS: Prostate cancer cells can be harvested from men with clinically localized disease undergoing sextant needle biopsy or radical prostatectomy. Routine prostate biopsy and surgery may influence the number of measurable circulating cells in the short term but the clinical significance and long-term prevalence of detectable circulating cells are unknown. Further studies are needed to evaluate the clinical usefulness of this assay for detecting, staging and monitoring prostate cancer.
Biopsy, Needle↗
Nuclear morphometry and prognosis in favorable histology Wilms' tumor: A prospective reevaluation.
PURPOSE: This study was designed to evaluate the ability of a previously published nuclear morphometry discriminant function to predict disease-free survival in patients with Wilms' tumor. PATIENTS AND METHODS: We identified 218 patients with stage I-IV Wilms' tumor of favorable histology who were entered onto the National Wilms' Tumor Study (NWTS) between January 1, 1990 and April 15, 1994. The nuclear morphometry score was calculated for each patient as follows: MV(f) = (0.02 x AGE) + (1.17 x SNRF) + (90.6 x LEFD) - 94, with AGE denoting age at diagnosis in months, SNRF the skewness of the nuclear roundness factor, and LEFD the lowest value of nuclear ellipticity as measured by the feret diameter method. Relative risks of relapse were estimated for the total score and for each of its components. Sensitivity and specificity were determined for the criterion of "MV(f) is greater than -0.35" as a predictor of relapse. RESULTS: By contrast with previously published results, neither the SNRF nor the LEFD made any contribution to the prediction of disease-free survival. Sensitivity and specificity of the criterion of "MV(f) is greater than -0.35" were 71% and 56%, respectively. CONCLUSION: Re-evaluation of a published nuclear morphometry score showed that it did not predict disease-free survival in patients with Wilms' tumor. The earlier study very likely overestimated the predictive power of nuclear morphometry by using the same data set both to develop the score and to evaluate its properties. Because of the huge number of combinations of nuclear morphometry measurements that may enter into the multivariate discriminant function, use of appropriate statistical methods is essential to estimate accurately the sensitivity and specificity.
Child↗
Long-term effects of finasteride on prostate tissue composition.
OBJECTIVES: To determine the long-term effects of finasteride treatment on prostate tissue composition; to relate these effects to clinical outcomes; and to test the hypothesis that finasteride exerts a selective or preferential action on the transition zone. METHODS: Nineteen men with symptomatic benign prostatic hyperplasia (BPH) who completed a 6-month double-blind trial of finasteride were enrolled in a 24-month open-label extension study of drug responders. Magnetic resonance imaging and prostate biopsy for morphometric analysis were performed together 70 times: at baseline (n = 19), after treatment periods of intermediate duration (6 to 18 months, n = 32), and after long-term drug treatment (24 to 30 months, n = 19). At baseline, prostate volume averaged 51 cc, of which 57% was transition zone. RESULTS: Decreases in symptom score, dihydrotestosterone and prostate-specific antigen levels, and prostate volume occurred at 6 months (P <0.01), stabilized, and were maintained without further long-term decreases. Prostate epithelium contracted progressively from baseline (19.2% tissue composition; 6.0-cc volume; 3.2 stroma/epithelial ratio) to intermediate (12.5%, 3.3 cc, and 5.6, respectively) to long-term treatment (6.4%, 2.0 cc, and 17.4, respectively, P <0.01 for all). Percent epithelial contraction was similar in the peripheral and transition zones (P = NS). The transition zone remained a relatively constant proportion (53% to 58%) of whole-prostate volume from baseline to long-term observation. CONCLUSIONS: Long-term finasteride treatment (24 to 30 months) results in a marked involution of the prostate epithelium, which continues to progress for many months after clinical effects stabilize. The effect on the epithelium is similar in the peripheral and transition zones for both morphometric and volumetric changes. Progressive contraction of the prostate epithelium appears to constitute the underlying mechanism for sustained action of finasteride.
Double-Blind Method↗