Biomedical subjects

A W Partin

Publications and source records attributed to A W Partin.

At least 163 records · Page 9Linked to original sources

PubMed1996

Multicenter comparison of the diagnostic performance of free prostate-specific antigen.

OBJECTIVES: This study examined the multicenter clinical performance of noncomplexed (free) prostate-specific antigen (PSA) in men presenting with total PSA values between 2.5 to 20 ng/mL. METHODS: Prebiopsy serum samples were obtained from 1,081 consecutively accrued, histologically diagnosed men between the ages of 40 and 75 years with total PSA values falling between 2.5 and 20 ng/mL. Total PSA was determined by either the Tosoh AIA-1200 or Hybritech method. Free PSA values were determined using the Dianon PSA II immunoradiometric method. Free PSA was expressed as a percentage of total PSA. Immunochemistry was performed at each accrual site. RESULTS: Among men diagnosed with prostate cancer (CaP), only 4% (21/520) had proportions of free to total PSA values > 25%. Conversely, among men with benign prostatic disease, only 2% (13/561) had proportions of free to total PSA values < 7%. These results confirm those of previous research. Differences among sites were found in age and prostate volume. CONCLUSIONS: These data confirm that free PSA values < 7% are highly suspicious for CaP whereas free PSA values > 25% suggest absence of malignancy. The data also suggest that age and/or prostate volume influences the serum level of free PSA but does not affect the diagnostic cutoff points of 7% and 25%. Future analysis is needed to confirm that younger men with small prostates are at higher risk for CaP.

Adult↗

PubMed1996

The role of free/total prostate-specific antigen ratio in the prediction of final pathologic stage for men with clinically localized prostate cancer.

OBJECTIVES: The combined use of total prostate-specific antigen (PSA), clinical stage, and Gleason score accurately predicts final pathologic stage for men with clinically localized prostate cancer. Recently, the free/ total PSA ratio has been proposed as an adjunct for early detection of prostate cancer. We examined the association between free/total PSA and pathologic stage. METHODS: In a prospective study, 301 consecutive men with clinically localized prostate cancer (average age 58.8 years, range 45-72) underwent a staging pelvic lymphadenectomy and radical prostatectomy. Total PSA and free PSA were measured from preoperative sera. Pathologic stage was determined as organ-confined (OC, n = 169), capsular penetration (CP+, n = 108), seminal vesicle involvement (SV+, n = 13) and lymph node involvement (LN+, n = 11). RESULTS: Overall, 292/301 (97%) of the free/total PSA values were < 25%, and thus suspicious for prostate cancer. Combination of total PSA, Gleason score, and clinical stage predicted well OC (P = 0.00001) and LN+ (P = 0.023); whereas, replacing total PSA with free/total PSA ratio did not improve the prediction of OC (P = 0.0007) nor LN+ (P = 0.03). CONCLUSIONS: The free/total PSA ratio cutoff point of 25% had high sensitivity for prostate cancer among a group of men with clinically localized disease. The free/total PSA ratio did not significantly improve the prediction of pathologic stage provided by total PSA when used alone or in combination with Gleason score and clinical stage. These preliminary data demonstrate that free/total PSA levels provide no additional information for pathologic stage prediction when combined with Gleason score and clinical stage in men with clinically localized prostate cancer.

Aged↗

PubMed1996

Analysis of percent free prostate-specific antigen (PSA) for prostate cancer detection: influence of total PSA, prostate volume, and age.

OBJECTIVES: To determine whether the use of the free-to-total PSA ratio (percent free PSA) could increase the specificity of PSA testing for prostate cancer detection in men with serum PSA concentrations between 4.0 and 10.0 ng/mL, and to assess the influence of total PSA, prostate volume, and age on percent free PSA. METHODS: Sera were obtained from 217 men with histologically confirmed diagnoses (139 prostate cancer, 78 benign). Free and total PSA concentrations were determined using Hybritech Tandem assays. RESULTS: Use of percent free PSA increased PSA specificity: 29% of negative biopsies would be spared while retaining 95% sensitivity. Percent free PSA increased with increasing age and prostate volume. Percent free PSA decreased as total PSA increased. A significant relation exists between percent free PSA and the probability of a positive biopsy; in this cohort, a patient with a low percent free PSA (< or = 10%) had a higher probability of cancer (63 +/- 9%) than a patient with a high percent free PSA (> or = 26%) (probability 2 +/- 3%). CONCLUSIONS: Percent free PSA may be used as an aid in distinguishing prostate cancer from benign disease in men with a total PSA between 4.0 and 10.0 ng/mL. Large prospective multicenter trials are required to develop consistent recommendations and determine the appropriate cutpoints and risk probabilities, controlling for total PSA, prostate volume, age, and biopsy history.

Adult↗

PubMed1996

Ureteral bladder augmentation using the lower pole ureter of a duplicated system.

Megaureters of nonfunctioning renal segments in a duplex system are commonly available for use in reconstructive procedures secondary to high-grade reflux, ectopic ureter, ectopic ureterocele, or obstructive megaureter. The use of megaureters subtending a nonfunctioning lower pole renal segment for bladder augmentation in 2 patients is reported.

Adolescent↗

PubMed1996

The use of prostate-specific antigen and free/total prostate-specific antigen in the diagnosis of localized prostate cancer.

Although there is controversy regarding the benefit of early detection of prostate cancer, it has been demonstrated that early detection can be best achieved through the use of a combination of digital rectal examination and prostate-specific antigen (PSA). This article outlines the clinical use of PSA for early detection of prostate cancer and focuses primarily on the value of molecular forms of PSA (free PSA, complexed PSA, and total PSA) in the diagnosis of localized prostate cancer.

Age Factors↗

PubMed1996

Prediction of progression following radical prostatectomy. A multivariate analysis of 721 men with long-term follow-up.

We studied 721 men with clinically confined disease who underwent radical prostatectomy. No patient received preoperative or postoperative radiotherapy or hormone therapy until progression occurred. For those men without progression, the mean follow-up was 6.5 years with a median of 6 years (range 1 to 12 years). Because patients with lymph node metastases or seminal vesicle invasion had such a high risk of progression, enhanced prognostication was not needed in men with these findings. Thus we focused this analysis on the 617 men without lymph node metastases or seminal vesicle invasion. In the multivariate analysis, Gleason score (P < 0.0001), surgical margins (P = 0.004), and capsular penetration (P = 0.007) were all independent predictors of progression. Tumors with a Gleason score of 2 through 4 were almost invariably cured, with a 10-year progression-free risk of 96%. At the opposite end of the spectrum, the 10-year actuarial progression-free risk for men with a Gleason score of 8 through 9 was 35%. Men with Gleason score 2 through 4 or 8 through 9 tumors could not be stratified into different risks of progression based on the presence or extent of capsular penetration or margin status. For the men with Gleason score 5 through 7 tumors (88.2% of cases), predicting their risk of progression was enhanced by knowledge of their tumor's capsular penetration and margin status. Tumors with a Gleason score of 5 through 6 and 7 were each stratified into three groups with different risks of progression. Using the actuarial curves within this study, physicians will be able to more accurately determine a patient's risk of progression following radical prostatectomy based on a combination of the radical prostatectomy Gleason score, extent of capsular penetration, and status of surgical margins of resection.

Disease Progression↗

PubMed1996

Extended followup of the influence of wide excision of the neurovascular bundle(s) on prognosis in men with clinically localized prostate cancer and extensive capsular perforation.

PURPOSE: The effect of wide excision of the neurovascular bundles on disease-free survival was determined in men with clinically localized prostate cancer and pathological evidence of extensive capsular perforation in the region of the neurovascular bundle. MATERIALS AND METHODS: We previously analyzed 107 men with clinically localized prostate cancer and pathological evidence of extensive capsular perforation in the region of the neurovascular bundles. Wide excision of the neurovascular bundle on the sides of palpable induration resulted in negative surgical margins in 58% of patients compared to only 45% in whom the neurovascular bundles were left intact (p = 0.03). At a mean followup of 20 months, median interval to disease recurrence as defined by a measurable PSA level was 33 months in patients whose neurovascular bundle(s) were widely excised versus 22 months in those whose neurovascular bundle(s) were left intact (p = 0.03). However, by 43 months 75% of the patients in both groups had a detectable prostate specific antigen and the Kaplan-Meier curves had converged, suggesting that wide excision of the neurovascular bundle(s) did not confer a sustained survival advantage. RESULTS: With an additional followup of 28 months, the probability of having an undetectable prostate specific antigen level at 5 years was 47% in patients with negative versus 6% with positive surgical margins (p < 0.001). CONCLUSIONS: Our extended followup suggests that some patients with extensive capsular perforation can be rendered free of disease with wide excision of the neurovascular bundle(s).

Actuarial Analysis↗

PubMed1996

Standard versus age-specific prostate specific antigen reference ranges among men with clinically localized prostate cancer: A pathological analysis.

PURPOSE: Age-specific prostate specific antigen (PSA) references ranges have been suggested to account for the age-dependent nature of the serum PSA concentration. It has been hypothesized that reference ranges of 0 to 2.5 ng./ml.serum PSA (40-49 years), 0 to 3.5 ng./ml. (50-59 years), 0 to 4.5 ng./ml. (60 to 69 years) and 0 to 6.5 ng./ml. (70 to 79 years) would detect fewer (potentially insignificant) prostate cancers in older men and more (potentially curable) cancers in younger men. MATERIALS AND METHODS: To investigate the pathological stage of tumors that would be affected by the use of age-specific PSA references ranges, we reviewed the medical records for 4,597 men with clinically localized (stage T1c, T2, or T3a) prostate cancer, with an average age of 62 +/- 7 years (range 38 to 76), who underwent radical prostatectomy between 1984 and 1994 at our institutions. Favorable pathological results were defined as organ-confined disease or capsular perforation with a Gleason score of less than 7, and unfavorable pathological results were defined as capsular perforation with a Gleason score of 7 or more, seminal vesicle invasion or lymph node involvement. RESULTS: Overall, 18% of the men had PSA levels less than the standard PSA reference range (4.0 ng./ml.) compared to 22% when using the age-specific ranges. There were 74 more cancers detected in men younger than 60 years with the use of age-specific ranges, of which 81% had favorable pathological results. Among the men 60 years or older, 191 of 252 cancers (76%) not detected by using age specific ranges less than 3% were also stage T1c and 95% of these undetected T1c cancers were of favorable pathological status. Of those cancers not detected in older men with the age-specific ranges were of favorable pathological status. Of those cancers not detected in older men with age-specific ranges less than 3% were also stage T1c and 95% of these undetected T1c cancers were of favorable pathological status. Age-specific PSA reference ranges increased the potential for detection of prostate cancer by 18% in the younger men and decreased the detection by 22% in the older men. CONCLUSIONS: Among these men with clinically localized prostate cancer, age specific PSA references ranges increased the detection of more potentially curable tumors in young men and decreased the detection of less advanced tumors in the older men compared to the standard reference range of 4.0 ng./ml. Among older men with nonpalpable (stage T1c) tumors age-specific PSA references ranges would have detected fewer tumors. However, 95% of these "missed" tumors would have had favorable pathological findings.

Adult↗

PubMed1996

Serum prostate specific antigen levels after transurethral resection of prostate: a longitudinal characterization in men with benign prostatic hyperplasia.

PURPOSE: We studied the long-term effects of adenomectomy on serum levels of prostate specific antigen (PSA) in men with benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: A consecutive series of 82 men undergoing adenomectomy for BPH between 1990 and 1992 was studied. PSA levels were determined before and serially after operation for as long as 5 years. RESULTS: Mean PSA decreased from 4.6 ng/ml. preoperatively to 0.7 ng./ml. 6 months postoperatively. These low levels were maintained throughout the 5-year observation period. The PSA decrease correlated with grams of tissue removed (r = 0.54, p < 0.001) and averaged 0.11 ng./ml./gm. Postoperatively mean PSA velocity was 0.01 ng./ml. per year, that is essentially flat, and it was not influenced by patient age, race, type of operation, grams of tissue removed, baseline PSA, PSA density of T1a lesions (7). One to 5 years after adenomectomy 6 of the 82 men had invasive prostatic carcinoma, and PSA levels and velocities remained low. CONCLUSIONS: These data support the concept of transition zone primacy in determining serum PSA. Furthermore, they suggest a possible need for a modified reference range when using PSA to screen for prostatic carcinoma in the estimated 3 million men alive in the United States who previously underwent adenomectomy for BPH.

Adult↗

PubMed1996

Evaluation of smooth muscle and collagen subtypes in normal newborns and those with bladder exstrophy.

PURPOSE: Many patients who undergo bladder exstrophy closure as newborns, subsequent epispadias repair and later bladder neck reconstruction become completely continent yet complications can occur. After successful initial exstrophy closure and later epispadias repair some patients may fail to gain sufficient capacity for bladder neck reconstruction or satisfactory capacity and continence after bladder neck reconstruction. In an attempt to understand the pathogenesis of these failures we compared bladder biopsies from normal neonates and those with exstrophy. MATERIALS AND METHODS: Bladder biopsies obtained from the midline of the bladder wall just above the base of the trigone from 12 newborns with exstrophy were compared to bladder sections from 9 neonatal cadavers. All bladder specimens were stained with monoclonal antibodies against type I, III or IV collagen and a subset was further stained with Masson's trichrome to define the extracellular matrix. All specimens were then analyzed using a color digital image analysis system. RESULTS: At initial examination of the extracellular matrix there was an increase in the collagen-to-smooth muscle ratio from 0.38 in controls to 1.2 in newborns with exstrophy, comprising an increase in collagen and decrease in smooth muscle. The collagen component of the extracellular matrix was then further defined to quantitate the amount of each collagen type (I, III and IV) deposited. We then evaluated the ratio of collagen type-to-total collagen sampled. Compared to control bladders there was no statistical difference in the amount of type I or IV in the bladders of newborns with exstrophy at initial closure. However, there was a 3-fold increase in type III collagen (0.14 +/- 0.05 to 0.46 +/- 0.2%, p < 0.001) in the bladders of neonatal controls versus newborns with exstrophy. CONCLUSIONS: This alteration in collagen makeup may represent an earlier developmental stage of the exstrophy bladder at birth, which then remodels and changes after successful initial closure. Further studies are underway to examine the collagen composition of bladders at bladder neck reconstruction, failed closures and augmentation.

Biopsy↗

PubMed1996

Clearance rate of serum-free and total PSA following radical retropubic prostatectomy.

BACKGROUND: Our objective was to determine the clearance rate of free and total serum PSA following radical retropubic prostatectomy. METHODS: Sera were obtained from 10 men with localized prostate cancer prior to and 1, 4, 8, 24, 48, and 72 hr after radical prostatectomy. No patient received any postoperative blood transfusion. Free and total PSA were measured using the Hybritech Tandem-R (total PSA) and radioimmunometric free PSA assay. Postsurgery serum-free and total PSA concentrations were modeled using a "two-compartment" pharmacokinetic model. RESULTS: The pharmacokinetic model with an initial constant "infusion" suggests that, following release from the prostate, both free and total PSA are taken up into a second compartment for metabolism. The movement of PSA between these compartments was accurately modeled. Following surgery, there is a shift of both free and total PSA best modeled as a constant infusion into the serum at a rate of 1.97 and 1.60 ng/ml, respectively, for a period of approximately 1 hr. Following this initial constant infusion, the half-life estimations for free and total PSA are initially 1.2 and 0.75 hr, respectively, which then increase to 22 and 33 hr, respectively. CONCLUSIONS: Serum free and total PSA are cleared from the circulation following a "two-compartment" model with an initial constant "infusion." The constant "infusion" is most likely a consequence of surgical manipulation. The initial half-life estimates are < 2 hr for both free and total PSA, and later increase to 22 and 33 hr, respectively.

Aged↗

PubMed1995

Radical surgery for renal-cell carcinoma: caval neoplastic excision, adrenalectomy, lymphadenectomy, adjacent organ resection.

A radical nephrectomy typically includes early ligation of the renal vessels, excision of the kidney and perinephric tissue, a regional lymphatenectomy, and an adrenalectomy. More controversial may be excision of supradiaphragmatic caval neoplastic extension and adjacent organ resection. Although survival is low in these unfavorable groups of patients, some patients may benefit from the extensive local resection of tumor, including adrenalectomy, lymphatenectomy, caval resection, and resection of adjacent organs.

Adrenalectomy↗

PubMed1995

Serum ferritin as a clinical marker for renal cell carcinoma: influence of tumor volume.

OBJECTIVES: At present, 35% to 50% of patients with clinically localized renal cell carcinoma (RCC) unpredictably have a recurrence after surgical therapy. Presently, no clinical serum marker exists to detect occult metastases and to allow measurement of response to therapy in RCC. Serum ferritin was previously reported to correlate with pathologic stage. We postulated that this increase in serum ferritin with increasing stage might reflect tumor volume, since higher stage tumors are often larger. METHODS: Serum ferritin levels were measured preoperatively in 30 patients with radiologic evidence of RCC. Tumor volume and the largest tumor dimension were calculated from either the pathologic specimen (n = 24) or from the computed tomography or magnetic resonance imaging (n = 30). Pathologic stage was determined for all patients undergoing surgery (T1 = 3, T2 = 12, and T3 = 9). RESULTS: Preoperative serum ferritin levels did not correlate with age, blood urea nitrogen levels, creatinine levels, hematocrit, race, or gender. Although mean serum ferritin levels increased with increasing stage (T1 = 113 +/- 75, T2 = 254 +/- 270, and T3 = 425 +/- 257 ng/mL), these differences did not reach statistical significance (P > 0.05). Serum ferritin did, however, correlate with tumor volume (R = 0.75; P < 0.0001) and the largest tumor dimension measured from radiographic studies (R = 0.8; P < 0.0001). Serum ferritin measured intraoperatively from the renal vein (666 ng/mL) and the inferior vena cava (564 ng/mL) from a patient with a 500 cc tumor (preoperative serum ferritin, 552 ng/mL) suggested that the tumor was the source of the elevated ferritin levels. Histologic sections from tumors taken from patients with high serum ferritin levels were more necrotic and stained intensely positively for iron and immunohistochemically for ferritin, whereas adjacent histologically normal tissue did not. CONCLUSIONS: These data suggest that ferritin may be a useful serum marker for monitoring patients with RCC, but the actual source of the ferritin remains unclear and dictates further investigation.

Adult↗

PubMed1995

Partial nephrectomy: technique, complications and pathological findings.

PURPOSE: We evaluate whether partial nephrectomy can be performed safely and efficaciously for renal tumors. MATERIALS AND METHODS: The results of 67 partial nephrectomies performed between 1977 and 1994 for renal cell carcinoma (51), oncocytoma (9), angiomyolipoma (3), transitional cell carcinoma (3) and other nonneoplastic lesions (2) were analyzed retrospectively in detail. RESULTS: Diminished complication rates were noted after 1988, and were attributed to improvements in surgical technique and an increased incidence of smaller, serendipitously discovered tumors. Although 35.5% of the patients had preoperative renal impairment (mean serum creatinine 2.1 mg./dl.), there were minimal changes in renal function and no patient required acute hemodialysis following partial nephrectomy. Among 42 patients with clinical stage T1 to T2 renal cell carcinoma undergoing partial nephrectomy local recurrence was identified in 8.3% of those with primary neoplasms. All 6 patients with local recurrence had negative surgical margins, recurrence often, distant from the operative site and multifocal disease, implicating multicentricity as the etiology of local recurrence. Five patients (83.3%) with local recurrence were alive and asymptomatic at a mean of 138 months after partial nephrectomy. Since capsular penetration was identified in 5 of 27 renal cell carcinomas (18.5%) with a diameter of 3.5 cm. or less, aggressive surgical resection with adequate tumor-free parenchymal and perinephric margins is necessary even for small lesions. CONCLUSIONS: With improved surgical techniques, including regional hypothermia, intraoperative sonography, meticulous dissection and injection of the collecting system with methylene blue, partial nephrectomy is safe and effective in properly selected patients.

Adolescent↗

PubMed1995

OA-519 (fatty acid synthase) as an independent predictor of pathologic state in adenocarcinoma of the prostate.

OBJECTIVES: To improve the prediction of pathologic stage beyond that provided by Gleason score. METHODS: We investigated the tissue expression in prostate cancer of a relatively new marker, oncoantigen 519 (OA-519). Because Gleason score is one of the most powerful predictors in prostate cancer, we restricted our evaluation to 66 radical prostatectomy specimens of varying pathologic stages which were either Gleason score 6 or 7. Immunohistochemical staining of OA-519 was assessed with a combined staining score from 0 to 8, taking into account both the intensity and percentage of tissue staining. In addition, an intensity score was derived based on whether any intense staining was present in case. RESULTS: OA-519 staining of the primary prostate cancer was highly predictive in separating cases with organ-confined disease or capsular penetration versus cases with seminal vesicle invasion or lymph node metastases; Gleason score 6 or 7 was also predictive. In a logistic multivariate regression analysis, both OA-519 and Gleason score were strong independent predictors of pathologic stage (P = 0.0004). CONCLUSIONS: OA-519 predicted pathologic stage well when analyzing primary prostate cancer in radical prostatectomy specimens and is presently being investigated on preoperative biopsy material to assess its ultimate clinical applicability. OA-519 has significant promise as a prognostic marker for prostate cancer and is one of the few markers that provides additional predictive information beyond that of the Gleason score.

Adenocarcinoma↗

PubMed1995

Nuclear morphometric analysis of metastasis in Wilms' tumor after multimodal therapy: comparison with primary tumor.

OBJECTIVES: The outlook for children with Wilms' tumor has improved with the use of multimodal therapy, and survival rates now exceed 85%. Yet, 15% of children with tumors with favorable histologic findings continue to recur unpredictably. We previously reported that nuclear morphometry (the distribution of nuclear roundness factor [NRF], lowest values for ellipticity, and age) when combined in a multivariate analysis accurately predicted response to therapy for patients with histologically favorable Wilms' tumors. METHODS: To investigate further the nuclear shape changes associated with disease recurrence, we analyzed histologic sections taken from primary tumors and postmultimodal therapy metastatic lesions for 7 children who had a recurrence with initially histologically favorable primary tumors. RESULTS: Mean NRF was significantly lower (P = 0.0001) in the metastatic lesion (35 +/- 5) group when compared with the primary tumor group (50 +/- 5). The percent coefficient of variation for NRF was also significantly lower (P = 0.006) in the metastatic lesion when compared with the primary tumor. Nuclear area was increased (P = 0.02), although the nuclear perimeter was unchanged (P = 0.1). CONCLUSIONS: (1) Nuclei in metastatic lesions from Wilms' tumors with favorable histologic findings after multimodal therapy are more round and exhibit less variable distribution, suggesting clonal homogeneity within the metastatic lesion. (2) Nuclei in the metastatic lesions have greater area than in the primary tumors yet have an unchanged perimeter, which may be due to internal nuclear expansion secondary to increased cellular deoxyribonucleic acid (DNA) ploidy. Although the results of this study are promising, we are currently extending this hypothesis to a larger group of patients.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

Relationship between changes in prostate-specific antigen and the percent of prostatic epithelium in men with benign prostatic hyperplasia.

OBJECTIVES: Pretreatment knowledge of prostate gland histology would allow a more scientifically based selection of medical therapy for men with benign prostatic hyperplasia (BPH) and may increase the effectiveness of the pharmacologic agents available. Changes in prostate-specific antigen (PSA), or PSA velocity, may reflect prostatic epithelial growth in BPH. Our objective was to determine if PSA velocity prior to diagnosis correlated with the relative amount of epithelium in BPH tissue. METHODS: We evaluated 39 men with BPH who had serial PSA determinations (mean, 5.4) on frozen sera from 2.3 to 25.1 years before diagnosis, and archival material from simple prostatectomy available for pathologic evaluation. We used an immunoenzymatic staining technique for PSA to bind prostatic epithelium selectively so that color differences in the stained tissue sections could be used to quantify stroma, epithelium, and glandular lumina. RESULTS: The average percentage of epithelium (%E) was 12.4 and the average stroma-epithelial ratio (SER) was 6.6. The correlation of PSA velocity for the three visits nearest to prostatectomy (n = 32) versus %E and SER was significant (P = 0.003 for both). The PSA value nearest to prostatectomy (n = 39) was directly correlated with %E and SER (P = 0.0001 and P = 0.001, respectively). CONCLUSIONS: These data suggest that PSA and PSA velocity are directly related to the histologic makeup of the prostate in men with BPH. Thus, pretreatment evaluation of PSA could be useful as part of an evaluation to direct BPH therapy.

Aged↗

PubMed1995

Selection of men at high risk for disease recurrence for experimental adjuvant therapy following radical prostatectomy.

OBJECTIVES: Following surgery, men with recurrent prostate cancer have an isolated elevation in serum prostate-specific antigen (PSA) well in advance of measurable metastatic disease. Rational patient selection for new forms of adjuvant therapy, for example, gene therapy, is imperative. METHODS: In a retrospective study of two cohorts, we used proportional hazards regression analysis to develop and validate a multifactor model for identifying men who are at high risk of cancer recurrence. The model cohort consisted of 216 men with clinical Stage T2b and T2c treated by 1 urologist. The validation cohort consisted of 214 men with Stage T2b and T2c disease. RESULTS: A model for log relative risk, Rw, used serum PSA with a sigmoidal transformation (PSAST), radical prostatectomy Gleason score (GS), and pathologic stage (PS) as specimen confined or nonspecimen confined: Rw = (PSAST x 0.06) + (GS x 0.54) + (PS x 1.87). Recurrence risk categories were determined as low risk if Rw is less than 4.0, intermediate risk if it is 4.0 to less than 5.75, and high risk if Rw is more than 5.75. The observed Kaplan-Meier actuarial analysis of the three risk groups correlated well with the predictions determined for the model cohort. We then validated this model independently using a second cohort of 214 men with similar age, stage, and grade treated by 3 different urologists at two different institutions. CONCLUSIONS: The recurrence rates for men in the high-risk group are similar to those for men with positive lymph nodes and justifies exploration of experimental adjuvant therapy within this group using this model of patient selection.

Actuarial Analysis↗