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W R Fair

Publications and source records attributed to W R Fair.

At least 55 records · Page 3Linked to original sources

Radical cystectomy in the octogenarian.

PURPOSE: We evaluated the morbidity and outcome of cystectomy and urinary diversion in patients 80 years old or older with invasive bladder cancer. MATERIALS AND METHODS: We reviewed the records of all patients older than 80 years who underwent cystectomy during the last 15 years. Of 1,186 cystectomies 44 patients (4%) were identified. Patients were evaluated for complications, mortality and functional status after surgery. RESULTS: The 44 patients had a median age of 81 years (range 80 to 87). Of the patients 78% had significant co-morbidity, including 41% with 2 or more medical problems. Median hospital stay was 14 days, with 20% of the patients requiring intensive care for 24 hours. There was a 51% complication rate including 25% due to surgical complications and 26% from underlying medical illness. Operative mortality was 4.5%. Within 6 months of surgery 66% were rehospitalized for medical or surgical reasons. Median survival time was 25 months. Median performance status before and after surgery decreased slightly from 70 to 65. CONCLUSIONS: The results of this study support the use of cystectomy in octogenarians with invasive bladder cancer. Surgery can be accomplished with acceptable morbidity and mortality. Radical cystectomy in this population offers the best opportunity for sustained disease-free quality survival.

Age Factors↗

Prognostic significance of prostate-specific antigen in stage T1c prostate cancer treated by radical prostatectomy.

OBJECTIVES: Increasingly, nonpalpable prostate-specific antigen (PSA)-detected (Stage T1c) tumors are being treated with curative intent. Presently, only limited information is available regarding pathologic findings correlated with preoperative PSA levels. Herein, we report the characteristics of Stage T1c tumors in a contemporary surgical series. METHODS: Clinical and pathologic results in 107 patients with Stage T1c tumors treated with radical prostatectomy were compared with those in 300 patients with palpable (Stage T2) tumors. Multivariate analysis was performed to determine which clinical variables independently predicted pathologic staging. RESULTS: Stage T1c tumors were equivalent to Stage T2 tumors with respect to organ-confined and margin-positive rates. PSA level was the strongest independent predictor of extracapsular and margin-positive rates (P = 0.003). The absence of palpability was not a significant predictor of pathologic outcome. Significantly higher rates of organ- and specimen-confined disease were seen in patients with PSA levels less than 10.0 ng/mL, particularly less than 7.0 ng/mL. Patients with serum PSA levels greater than 20 ng/mL were at high risk for positive margins (relative risk 5.42, P < 0.001). CONCLUSIONS: Stage T1c tumors represent a heterogeneous group of cancers. These tumors are pathologically similar to Stage T2 tumors, and patients should be offered similar treatment options. PSA level was the strongest predictor of pathologic stage, irrespective of tumor palpability. These results suggest that efforts directed toward identifying cancers, including nonpalpable tumors, in patients with early PSA elevations may result in improved rates of organ-confined disease. The impact of treatment on Stage T1c tumors remains to be defined.

Adult↗

The indications, rationale, and results of neoadjuvant androgen deprivation in the treatment of prostatic cancer: Memorial Sloan-Kettering Cancer Center results.

OBJECTIVES: The use of neoadjuvant chemotherapy prior to definitive surgery has been firmly established in other areas of oncology, most notably in the treatment to testis and Wilm's tumors. The use of neoadjuvant androgen deprivation therapy (ADT) in conjunction with radical prostatectomy remains a source of controversy. We have conducted phase II and phase III studies to assess the effects of 3 months of preoperative ADT (goserelin and flutamide) on the pathologic staging and postsurgery prostate-specific antigen (PSA) relapse rate. We also reviewed the data confirming the understaging of clinically localized prostatic cancer and the experimental data providing the conceptual support for ADT. METHODS: We report the results of 141 patients, Stage T0-T0, in a Phase II study with concurrent, nonrandomized controls (N = 72) versus a treatment arm (N = 69) of men receiving 3 months of ADT with 3.6 mg goserelin for 28 days and 750 mg flutamide daily. We also report the interim results in 114 men participating in a prospective, randomized study of ADT versus surgery alone. RESULTS: The 69 patients who received 3 months of goserelin and flutamide followed by radical prostatectomy had a pathologic organ-confined cancer rate of 74%, versus 48% in the control group who received no ADT prior to surgery. The margin-positive rate was 10% in the ADT group versus 33% in the control group. In an interim analysis of 114 patients (59 ADT, 55 control), the organ-confined and margin-positive rates were 73% and 17% in the ADT group versus 56% and 36% in the control arm, respectively. The PSA disease-free rate at a mean follow-up of 28.6 months (range 6.2 to 49.5 months) was 89% in the ADT-treated patients (N = 98) and 84% in the control patients (N = 96). There was no statistical difference demonstrated between the arms with respect to biochemical failure. CONCLUSIONS: While the pathologic staging of tumors following ADT treatment was improved compared with surgical controls, to date the PSA disease-free survival rates are similar. Patients with residual extracapsular (P3) disease after ADT manifest an increased PSA failure rate compared with those with P3 tumors treated by surgery alone. This suggests that ADT may identify a subset of patients with aggressive tumors that may be candidates for additional therapeutic interventions even before PSA failure occurs.

Aged↗

Evaluating neoadjuvant therapy effectiveness on systemic disease: use of a prostatic-specific membrane reverse transcription polymerase chain reaction.

OBJECTIVE: An on-going study at the Memorial Sloan-Kettering Cancer Center assessed the effectiveness of androgen deprivation therapy (ADT) prior to surgical removal of the prostate. In this report, we evaluate the effectiveness of ADT on systemic disease by monitoring the presence or absence of circulating prostatic epithelial cells using a reverse transcription polymerase chain reaction (RT-PCR) assay for prostatic-specific membrane antigen (PSM). METHODS: PSM RT-PCR was performed on a total of 38 prostate cancer patients. There were 12 pT2 patients in the ADT group and 10 patients in the control pT2 group and 5 pT3 patients in the ADT group and 11 pT3 patients in the control group. RESULTS: For pT2 patients, 2 of the 12 patients (17%) were positive for circulating prostatic cells during androgen deprivation therapy but before radical retroprostatectomy (RRP). Within a 6-month period after RRP, 3 of 12 patients (25%) were positive. For the period between the 7th and 12th month after RRP, 6 of 12 patients (50%) were positive. For the period 12-36 months after RRP, 2 of the 12 patients (17%) remained positive for circulating prostatic cells. In contrast, the pT2 control group had higher positive rates in comparable periods: 4 of 10 patients (40%) were positive prior to surgery; 6 of 10 patients (60%) were positive during the 6 months following surgery. For the period between the 7th and 12th month following surgery, 4 of 7 patients (57%) were positive for PSM. Finally, 3 of 6 patients (50%) were positive for the period longer than 12 months. Regarding patients who have extraprostatic disease (stage pT3), the ADT group had a lower rate of circulating PSM positive cells. Before RRP and during androgen deprivation therapy, 1 out of 5 patients (20%) in the ADT group were positive as compared to 4 out of 11 patients for the control group. Within a 6-month period after RRP, the ADT group had 4 out of 9 (44%) patients positive for PSM as compared to 9 of 11 (82%) for the control group. For the period between the 7th and 12th months postsurgery, 1 of 5 patients (20%) of the ADT group were positive as compared to 4 of 7 (57%) of the control patients. CONCLUSIONS: These results indicate that patients with pT2 and pT3 lesions who receive neoadjuvant ADT are less likely to have circulating tumor cells detected compared to a control group both prior to and after surgery. In addition, irrespective of ADT or control group, there were increases in the detection of circulating tumor cells in the period after RRP, and this rise gradually decreased, suggesting that surgical manipulation may cause hematogenous dissemination of tumor cells and that ADT reduces such dissemination of tumor cells. Overall, these results indicate that the use of neoadjuvant ADT decreases the number of circulating prostatic cells. These data represent the initial results of an on-going study. As additional patients are added to the studies, attempts to correlate PSM positivity and serum PSA values postoperatively, recurrence, and margin positivity will be made.

Androgen Antagonists↗

Clinical significance of repeat sextant biopsies in prostate cancer patients.

OBJECTIVES: Six random systematic core biopsies (SRSCB) of the prostate is considered by many to represent the standard method of detecting prostate cancer. We sought to evaluate the sensitivity of the transrectal ultrasound (TRU)S-guided needle biopsies in 89 consecutive patients with a history of biopsy-proven prostate cancer. These patients underwent repeat biopsy prior to enrollment in an ongoing, randomized protocol. We also compared the clinical and pathological features of patients with SRSCB-documented prostate carcinoma and negative repeat-sextant biopsy. METHODS: Our study population consisted of 89 patients enrolled in our randomized, prospective study assessing the effect of androgen deprivation therapy in combination with radical prostatectomy for clinically localized prostate cancer. A comparison was made of the patients' rebiopsy results with initial biopsy. Patients having either a positive or negative rebiopsy were analyzed with respect to grade, T stage, prostate-specific antigen (PSA), PSA density (PSAD), organ-confined rate, and final surgical margin status. RESULTS: Repeat sextant biopsy was positive for prostate cancer in 71 (80%) patients and negative in 18 (20%) patients. There was no significant difference between patients with a negative or positive rebiopsy with respect to PSA or PSAD. There was a trend toward greater prostate volumes in the negative-rebiopsy group (P = 0.08) and lower clinical stage in the negative rebiopsy (P = 0.025) group. In patients with a negative repeat biopsy, the organ-confined (OC) rate was 77% (14/18 patients), as compared to the positive-rebiopsy group of 56% (40/71 patients) (P = 0.08). Similarly, the margin-positive rate in the negative-rebiopsy group was 17% (3/18 patients), as compared to the positive-rebiopsy group who had a margin-positive rate of 44% (31/71 patients) (P = 0.03). CONCLUSIONS: In patients with clinically localized disease, the sensitivity of SRSCB in detecting carcinoma is 80%. The results of this study highlight the potential sampling error of the SRSCB and the implication of a negative rebiopsy in patients with clinically significant prostate cancer.

Androgen Antagonists↗

Cancer of the prostate: a nutritional disease?

UNLABELLED: In summary, epidemiologic and laboratory evidence increasingly demonstrate that nutritional factors, especially reduced fat intake, soy proteins, vitamin E derivatives, and selenium, may have a protective effect against prostate cancer. The experimental observation that low-fat diets and soy protein extracts may influence the progression of established tumors, rather than inhibiting etiologic factors, is particularly intriguing because it may serve to help explain the paradox whereby the incidence of clinical prostate cancer shows wide geographic variation, yet the evidence persists that the incidence of microfocal tumors is essentially the same worldwide. These observations, plus the likelihood that nutrition trials are likely to have little in the way of toxicity that would preclude their completion, argue that such trials should be performed. It is estimated that 30% to 50% of human malignancies may be related to dietary factors, and although the feasibility of trials involving low-fat diets has been proved in ongoing trials for colon and breast cancer, no similar study exists for prostate malignancy. Critics of epidemiologic research argue that data derived from case-control studies are subject to recall bias and are thus artifactual. Indeed, many researchers now believe that the breast cancer-dietary fat hypothesis has been discredited. The major difference between the prostate cancer and breast cancer literature is the remarkable consistency of the cohort studies. In these studies, exposure is determined prospectively and is therefore free from recall bias. In this sense they more closely resemble a clinical trial. The majority of cohort studies involving dietary fat and breast cancer have been negative. We believe that these data justify large-scale trials in the area of prevention of prostate cancer. One such proposed study already submitted for National Institutes of Health funding from a consortium of centers is the Prostate Interventional Nutrition Study (PINS), modeled after the Women's Interventional Nutrition Study, which investigates the effect of low-fat diets in women receiving therapy for node-positive breast cancer. The PINS study will be limited to men who have detectable serum PSA levels but no other clinical evidence of disease after radical prostatectomy. All subjects will receive nutritional guidance, with randomization between a control arm receiving the currently recommended 30% fat diet and an interventional arm in which a 15% fat diet is supplemented with soy protein, vitamin E, and selenium. The end points for evaluation will be compared with progression based on changes in PSA and the time of onset of clinical, as opposed to biochemical, disease. Single-institution trials involving groups thought to be at high risk of developing clinical cancer--including men with persistently elevated PSA levels, two negative prostate biopsies, high-grade prostatic intraepithelial neoplasia on biopsy, and a strong family history of prostate cancer--are being initiated at MSKCC and other institutions. CONCLUSIONS: We have reviewed the evidence that nutritional factors play a role in the progression rate of prostate cancer and may help to explain the geographic variation in the incidence observed. However, without well-controlled prospective trials, the attractive hypothesis that nutrition plays a role in tumor progression remains simply an attractive hypothesis. To date, no definite proof of a preventive effect has been shown in a study that will withstand rigid scientific scrutiny. The opportunity exists, however, for the urologic community, working together with experts in the area of nutrition, not only to advance our understanding of prostate tumorigenesis, but to rebut those critics of modern medical technology who claim that we have ignored the total or holistic approach to healing. (ABSTRACT TRUNCATED)

Animal Nutritional Physiological Phenomena↗

Prostate-specific membrane antigen and other prostatic tumor markers on the horizon.

The PSM antigen is an exciting new molecule with many potentially valuable applications. Further research with PSM may help us to elucidate the complex process of prostatic neoplasia better. Current avenues of research with PSM include the generation of new and improved monoclonal antibodies targeting different portions of PSM and PSM', which may improve the results of imaging and targeting prostate cancer. Gene therapy using the PSM promoter to drive prostate-specific expression of various cytokines and other factors is another exciting potential application deserving of attention, and refinement of serum PSM assays may greatly add to the present array of diagnostic modalities offered to patients with suspected prostate cancer. Thus, PSM is a potentially valuable addition to our armamentarium of prostate markers. Additionally, a host of other potential markers to increase our understanding of the complex biology of the normal and malignant prostate are on the horizon. Just how far away that horizon is awaits further basic and clinical investigations.

Antigens, Neoplasm↗

Pathological staging and biochemical recurrence after neoadjuvant androgen deprivation therapy in combination with radical prostatectomy in clinically localized prostate cancer: results of a phase II study.

OBJECTIVES: To assess the pathological staging and biochemical progression-free survival (assessed using serum prostate-specific antigen level) of patients with clinically localized prostate cancer using neoadjuvant androgen deprivation therapy (ADT) in combination with radical retropubic prostatectomy (RRP). PATIENTS AND METHODS: A prospective study was carried out on 69 patients with localized prostate cancer who were enrolled in a trial of 3 months of ADT followed by RRP (group 1). These patients were compared with 72 patients matched for age and clinical stage who declined ADT therapy and had RRP concurrently (group 2). Assignment to the individual treatment groups was thus determined by the patient's preference and not the physician's selection. Pathological staging and biochemical progression-free recurrence were compared between the groups. RESULTS: The rate of organ-confined (pT2) tumours was 74% in group 1 and 49% in group 2 (P < 0.01), and the rate of margin-negative tumours was 87% in group 1 and 64% in group 2 (P < 0.01). Within a median follow-up of 35 months, there was no significant difference in biochemical failure between the groups (P = 0.37). Patients with pT2 disease, regardless of treatment, had similar biochemical failure rates. In the patients with margin-positive disease, there was a significantly higher biochemical failure rate in group 1 (P = 0.02). CONCLUSIONS: The rates of organ- and specimen-confined disease were higher among the patients treated with ADT. The preliminary follow-up suggested that patients with pT2 disease after ADT have a biochemical progression-free recurrence rate similar to pT2 patients treated with RRP alone. Additionally, high biochemical failure rates in patients with margin-positive disease after ADT may identify a subset of more biologically aggressive tumours in need of early adjuvant treatment.

Aged↗

The treated natural history of high risk superficial bladder cancer: 15-year outcome.

PURPOSE: The long-term outcome of patients with high risk superficial bladder cancer is unknown. We report the results of 15 years of followup of high risk patients treated initially with aggressive local therapy, including transurethral resection alone or combined with intravesical bacillus Calmette-Guerin. MATERIALS AND METHODS: Between 1978 and 1981, 86 high risk patients enrolled in a randomized study of transurethral resection alone or with intravesical bacillus Calmette-Guerin for superficial bladder cancer. Of these patients 81% had diffuse carcinoma in situ and 44% had stage T1 tumors before entry into the study. Patients were followed until death (61%) or until the present time (median followup 184 months). RESULTS: Disease stage progressed in 46 patients (53%) and 31 (36%) eventually underwent cystectomy for progression (28) or refractory carcinoma in situ (3), while 18 (21%) had upper tract tumors at a median of 7.3 years. The 10 and 15-year disease specific survival rates were 70 and 63%, respectively. At 15 years 34% of patients overall were dead of bladder cancer, 27% were dead of other causes and 37% were alive, including 27% with an intact functioning bladder. CONCLUSIONS: Despite aggressive local therapy patients with high risk superficial bladder cancer are at lifelong risk for development of stage progression and upper tract tumors. A third of patients are at risk for death from bladder cancer, justifying careful and vigilant long-term followup. These results support the use of initial aggressive local therapy in patients with high risk superficial bladder cancer.

Disease Progression↗

Ureteral carcinoma in situ at radical cystectomy: does the margin matter?

PURPOSE: The clinical impact of ureteral carcinoma in situ identified at the time of radical cystectomy for bladder cancer has been poorly studied. We discuss our experience with this clinical problem in the context of published reports. MATERIALS AND METHODS: A total of 31 patients with concomitant ureteral carcinoma in situ was retrospectively identified among 401 consecutive radical cystectomies. End points analyzed included positive urinary cytology, upper tract recurrence of carcinoma and cancer specific survival. RESULTS: Ureteral margins were positive in 21 patients and negative in 10. Among 30 patients in whom it was performed frozen section failed to detect carcinoma in situ in 5 (16.6%) and sequential ureteral resection did not result in a negative margin in 15 (50%). In 3 patients upper tract carcinoma recurred at the anastomosis (1) and renal pelvis/ureter (2) at a median of 51 months (mean 49, range 36 to 59) following cystectomy. Positive cytology and upper tract carcinoma recurrence were not significantly associated with ureteral margin status, clinical or pathological bladder tumor stage or prior bacillus Calmette Guerin treatment. Median followup was 22.9 months (mean 31.8, range 2.0 to 74.2), during which 7 of the 31 patients died of metastatic bladder cancer. CONCLUSIONS: Concomitant ureteral carcinoma in situ is uncommon, and is rarely associated with local morbidity. It appears to confer increased risk for upper tract carcinoma recurrence, irrespective of margin status. In our experience upper tract carcinoma recurrence is heralded by positive cytology and generally appears only with protracted followup. Prognosis appears to be determined by the bladder tumor. Given the lack of morbidity and mortality attributable to concomitant ureteral carcinoma in situ, and the limited ability of frozen section examination to assist in its extirpation, the value of intraoperative identification of concomitant ureteral carcinoma in situ is questionable and expectant management is advised.

Adult↗

Indications for transition zone biopsy in the detection of prostatic carcinoma.

PURPOSE: We determined the indications for transition zone biopsy in the detection of prostatic carcinoma. MATERIALS AND METHODS: A total of 185 men underwent 204 transition zone prostate biopsies due to elevated prostate specific antigen (PSA) alone in 19 (group 1), with hypoechoic transition zone lesions in 10 (group 2) and with a previous negative transrectal ultrasound guided biopsy in 156 (group 3). In addition, 13 men underwent 19 repeat transition zone biopsies. RESULTS: Of the patients 58 (31.4%) had positive biopsies, with 8 (4.3%) having cancer in the transition zone biopsies only. In 3 men with positive peripheral and transition zone biopsies the cancer was upgraded based on the transition zone specimens. No patient with elevated PSA and no previous biopsy (group 1) or sonographic transition zone abnormalities (group 2) had a positive transition zone biopsy only. None of the analyzed risk factors (age, PSA, prostate volume, PSA density or PSA velocity) was significantly greater in men with isolated transition zone tumors. CONCLUSIONS: Routine transition zone biopsies should be reserved for patients with previously negative transrectal ultrasound guided biopsies. In some patients disease upgrading based on transition zone biopsies may influence treatment decisions.

Aged↗

Correlation between Gleason score of needle biopsy and radical prostatectomy specimen: accuracy and clinical implications.

PURPOSE: Despite the reliability of Gleason grading with respect to the same specimen, the correlation between the biopsy and prostatectomy specimen is less well defined. We compared the accuracy of Gleason grading of biopsies in predicting histological grading of radical retropublic prostatectomy specimens. MATERIAL AND METHODS: Gleason scores of 18 gauge needle biopsies were compared to those of radical retropublic prostatectomy specimens in 226 consecutive patients. In addition to comparing numeric discrepancies, differences between biopsy and specimen Gleason scores of 2 or more and a change in group from Gleason scores 2 to 4, 5 to 7 or 8 to 10 were evaluated by kappa testing, as well as any change in group from Gleason scores 2 to 4, 5 and 6, 7 and 8 to 10. RESULTS: The biopsy score was identical to the specimen score in 31% of cases, while 26% were discrepant by 2 or more Gleason scores. Overall, 54% of biopsies were under graded, while 15% were over graded. If only cases in which discrepancies of 2 or more Gleason scores and a change in group were considered, there was good overall agreement (kappa 0.468, accuracy 80%). Among the cases with any change in group, the accuracy was only 46% with poor agreement (kappa 0.153). CONCLUSIONS: Overall, the reliability of Gleason grading of needle biopsies in predicting final pathology was good. However, the limitations of Gleason grading based on biopsy should be considered when discussing treatment options and comparing results based on biopsy data.

Adult↗

Glutathione S-transferase PI (GST-pi) class expression by immunohistochemistry in benign and malignant prostate tissue.

PURPOSE: Glutathione S-transferase (GST) enzymes may prevent carcinogenesis through inactivation of reactive electrophiles by conjugation to reduced glutathione. Recently, it was reported that most prostate cancers fail to express GST-pi despite an abundant presence in benign prostate tissue, suggesting a common genetic alteration. To define its presence in prostate tissue, we evaluated GST-pi expression in a variety of prostate tissues. MATERIALS AND METHODS: Immunostaining with anti-GST-pi antibody was performed on 69 benign prostates, 44 malignant prostates, 12 incidental prostate carcinomas and 17 prostatic intraepithelial neoplasia (PIN) specimens. Specimens were evaluated for the presence and percent of GST-pi. Within benign tissue, GST-pi immunostaining was distinguished between basal cells and secretory acinar epithelium. RESULTS: In benign epithelium, the basal cells demonstrated intense staining in all cases. The mean percent staining among the basal cells was 67% (R 40-90%). The acinar epithelium stained weakly positive in 94% (65/69) of specimens, however the mean percent staining was only 5% (R 0-25%). GST-pi was detected in only 3.5% (2/56) of the prostate cancers. No incidental prostate cancers and only one (6%) high grade PIN stained positive. CONCLUSIONS: Our study confirms the absence of GST-pi expression in prostate cancer and high grade PIN. Furthermore, GST-pi expression correlates well with the basal cell phenotype, but not with benign epithelial cells. The lack of staining among prostate cancer cells may reflect the absence of a basal cell layer, suggesting that GST-pi is involved more in epithelial differentiation and questioning its role in the malignant transformation of prostatic acinar cells.

Epithelium↗

Prostate cancer.

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Humans↗

Prevalence and predictors of a positive repeat transrectal ultrasound guided needle biopsy of the prostate.

PURPOSE: We determined the prevalence of and risk factors for carcinoma in patients with 1 previously negative prostate biopsy. MATERIALS AND METHODS: Transrectal ultrasound guided prostate needle biopsies were repeated in 130 men. Risk factors analyzed included age, pathological result of initial biopsy, inter-biopsy interval, prostate specific antigen (PSA), PSA density, PSA velocity, digital rectal examination, abnormal transrectal ultrasound and family history of prostate cancer. RESULTS: A total of 39 patients (30%) had positive biopsies for cancer. Univariate analysis revealed that PSA more than 20 ng./ml. and abnormal transrectal ultrasound were more frequent in men with positive second biopsies. Using multivariate logistic regression analysis only PSA more than 20 ng./ml. was a significant risk factor (adjusted odds ratio 4.48, 95% confidence interval 1.02 to 20.1). We determined the incidence of carcinoma in patients who represent the lowest risk group as defined by PSA less than 10 ng./ml., PSA density less than 0.15 mg./ml./cm.3, PSA velocity less than 0.75, ng./ml. per year, no prostatic intraepithelial neoplasia plus negative transrectal ultrasound, digital rectal examination and family history. Of 21 patients who fit this cohort 5 (23.8%) had carcinoma on repeat biopsy. CONCLUSIONS: A significant false-negative rate for initial transrectal ultrasound guided prostate biopsies exists. Baseline risk in lowest risk patients is sufficiently high such that one cannot define a subset of patients for whom repeat biopsy is unnecessary. We recommend repeat biopsy in all patients who meet the criteria for a transrectal ultrasound guided biopsy and in whom the initial biopsy is negative.

Biopsy, Needle↗

Neoadjuvant hormonal therapy plus surgery for prostate cancer. The MSKCC experience.

This article reviews the current status of neoadjuvant hormonal therapy (NHT) in the treatment of clinically localized prostate cancer. Although significant increases in the organ confined rate and similar marked decreases in the positive margin rate are found in patients receiving NHT, to date no difference in disease free survival rate, as determined by PSA values, can be shown. However, there is a suggestion (P = 10 ng/ ml when treated with NHT compared with controls. Given the prolonged natural history of prostate cancer, longer follow-up will be required before the value of NHT can be established.

Antineoplastic Agents, Hormonal↗

Prostate-specific membrane antigen expression in normal and malignant human tissues.

Prostate-specific membrane antigen is a type II membrane protein with folate hydrolase activity produced by prostatic epithelium. The expression of this molecule has also been documented in extraprostatic tissues, including small bowel and brain. In the present study, an extensive immunohistochemical analysis was performed on a panel of well-characterized normal and malignant human tissues to further define the pattern of prostate-specific membrane antigen (PSMA) expression. Detectable PSMA levels were identified in prostatic epithelium, duodenal mucosa, and a subset of proximal renal tubules. A subpopulation of neuroendocrine cells in the colonic crypts also exhibited PSMA immunoreactivity. All other normal tissues, including cerebral cortex and cerebellum, had undetectable levels of PSMA. Thirty-three of 35 primary prostate adenocarcinomas and 7 of 8 lymph node metastases displayed tumor cell PSMA immunostaining. Eight of 18 prostate tumors metastatic to bone expressed PSMA. All of the other nonprostatic primary tumors studied had undetectable PSMA levels. However, intense staining was observed in endothelial cells of capillary vessels in peritumoral and endotumoral areas of certain malignancies, including 8 of 17 renal cell carcinomas, 7 of 13 transitional cell carcinomas, and 3 of 19 colon carcinomas. Extraprostatic PSMA expression appears to be highly restricted. Nevertheless, its diverse anatomical distribution implies a broader functional significance than previously suspected. The decrease in PSMA immunoreactivity noted in advanced prostate cancer suggests that expression of this molecule may be linked to the degree of tumor differentiation. The neoexpression of PSMA in endothelial cells of capillary beds in certain tumors may be related to tumor angiogenesis and suggests a potential mechanism for specific targeting of tumor neovasculature.

Antigens, Neoplasm↗