Negative Prostate-specific Antigen Research Articles

Validation of a nomogram to predict disease progression following salvage radiotherapy after radical prostatectomy: results from the SEARCH database

To externally validate the nomogram published by Stephenson et al. (termed the 'Stephenson nomogram') to predict disease progression after salvage radiotherapy (SRT) among patients with prostate cancer from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We analysed data from 102 men treated with SRT for prostate-specific antigen (PSA) failure after prostatectomy, of whom 30 (29%) developed disease progression after SRT during a median follow-up of 50 months. The predicted 6-year progression-free survival (PFS) was compared to the actuarial PFS using calibration plots. The accuracy of the nomogram to risk-stratify men for progression was assessed by the concordance index. The median PSA and PSA doubling time before SRT was 0.6 ng/mL and 10.3 months, respectively. The 6-year actuarial disease-free progression after SRT was 57% (95% confidence interval 42-69%). The overall concordance index of the Stephenson nomogram was 0.65. The nomogram predicted failure more accurately at the extremes of risk (lowest and highest) but in intermediate groups, the accuracy was less precise. Of the 11 variables used in the nomogram, only negative margins and high PSA level before SRT were significantly associated with increased disease progression. The Stephenson nomogram is an important tool to predict disease progression after SRT following radical prostatectomy. It adequately predicted progression in SEARCH with reasonable accuracy. Also, in SEARCH, disease progression was predicted by similar disease characteristics. However, the overall modest performance of the model in our validation cohort indicates there is still room for improvement in predictive models for disease progression after SRT.

Detection of prostate specific transcripts in the peripheral blood during brachytherapy predicts postoperative PSA kinetics

We evaluated whether detection of prostate-specific antigen (PSA) and human kallikrein 2 (hK2) transcripts in the peripheral blood during brachytherapy could predict biochemical outcome. Eighty-one patients who underwent (125)Iodine-based brachytherapy for localized prostate cancer (Gleason score <8, PSA <20 ng/ml, stage <T3), participated in the study. Brachytherapy was given to 35 patients as monotherapy, to 36 in combination with androgen deprivation therapy (ADT), and to 10 in combination with external beam radiation and ADT. Blood samples from 80 patients were available for analysis. Nested RT-PCR means was used to detect mRNA expression of PSA and hK2 in the peripheral blood. Their expression was analyzed before, during and 1 month after brachytherapy. Patients' biochemical outcome (blood PSA levels) during 3 years of follow-up was correlated with the PCR results. The incidence of PSA and hK2 mRNA expression in the peripheral blood was significantly higher during than before or after the procedure. Patients with concurrent positive PSA and hK2 PCR results during brachytherapy had higher postoperative blood PSA values and a slower decline rate of PSA compared with patients with negative PSA and hK2 PCR results. No correlations were found between pre- and postbrachytherapy PCR results and biochemical outcome. ADT was the only significant factor that affected PSA and hK2 mRNA expression during brachytherapy. Our short-term results suggest that detection of PSA and hK2 transcripts in the peripheral blood of prostate cancer patients during brachytherapy could serve as a predictor of biochemical outcome.

Lymphovascular invasion is an independent predictor of prostate‐specific antigen failure after radical prostatectomy in patients with pT3aN0 prostate cancer

To investigate the association of lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens with prostate-specific antigen (PSA) failure in patients with pT3aN0 prostate cancer (PCA). We retrospectively reviewed the clinical records of 94 patients with pT3aN0 PCA treated with RP alone. All of the 94 patients were prospectively observed without any treatment until PSA failure was confirmed. We investigated the association of LVI with the adverse pathological findings in RP specimens and the PSA failure-free survival rate. The Cox proportional hazard model was used to elucidate predictors of PSA failure. Median follow up was 47.4 months (quartile range 9.1 to 146.8). LVI was found in 26 (27.7%) of the 94 patients. In a multivariate analysis, PSA (P = 0.0054) and LVI (P = 0.015) were significant and independent predictors of PSA failure. Stratifying patients into four risk groups by LVI status and PSA level, the PSA failure-free survival rate in patients with negative LVI and PSA < or =10 ng/mL was significantly better than any other groups (positive LVI and/or PSA >10 ng/mL). Adjuvant therapy would not be indicated to patients with pT3aN0 PCA with negative LVI and PSA < or =10 ng/mL.

Immunohistochemical Differentiation of High-grade Prostate Carcinoma From Urothelial Carcinoma

The histologic distinction between high-grade prostate cancer and infiltrating high-grade urothelial cancer may be difficult, and has significant implications because each disease may be treated very differently (ie, hormone therapy for prostate cancer and chemotherapy for urothelial cancer). Immunohistochemistry of novel and established prostatic and urothelial markers using tissue microarrays (TMAs) were studied. Prostatic markers studied included: prostate-specific antigen (PSA), prostein (P501s), prostate-specific membrane antigen (PSMA), NKX3.1 (an androgen-related tumor suppressor gene), and proPSA (pPSA) (precursor form of PSA). "Urothelial markers" included high molecular weight cytokeratin (HMWCK), p63, thrombomodulin, and S100P (placental S100). TMAs contained 38 poorly differentiated prostate cancers [Gleason score 8 (n=2), Gleason score 9 (n=18), Gleason score 10 (n=18)] and 35 high-grade invasive urothelial carcinomas from radical prostatectomy and cystectomy specimens, respectively. Each case had 2 to 8 tissue spots (0.6-mm diameter). If all spots for a case showed negative staining, the case was called negative. The sensitivities for labeling prostate cancers were PSA (97.4%), P501S (100%), PSMA (92.1%), NKX3.1 (94.7%), and pPSA (94.7%). Because of PSA's high sensitivity on the TMA, we chose 41 additional poorly differentiated primary (N=36) and metastatic (N=5) prostate carcinomas which showed variable PSA staining at the time of diagnosis and performed immunohistochemistry on routine tissue sections. Compared to PSA, which on average showed 18.8% of cells with moderate to strong positivity, cases stained for P501S, PSMA, and NKX3.1 had on average 42.5%, 53.7%, 52.9% immunoreactivity, respectively. All prostatic markers showed excellent specificity. HMWCK, p63, thrombomodulin, and S100P showed lower sensitivities in labeling high-grade invasive urothelial cancer in the TMAs with 91.4%, 82.9%, 68.6%, and 71.4% staining, respectively. These urothelial markers were relatively specific with only a few prostate cancers showing scattered (<or=2%) weak-moderate positive cells. In summary, PSA can be used as the first screening marker for differentiating high-grade prostate adenocarcinoma from high-grade urothelial carcinoma. Immunohistochemistry for P501S, PSMA, NKX3.1, and pPSA are useful when high-grade prostate cancer is suspected based on the morphology or clinical findings, yet shows negative or equivocal PSA staining. HMWCK and p63 are superior to the novel markers thrombomodulin and S100P.

Prostate-Specific Antigen, High-Molecular-Weight Cytokeratin (Clone 34βE12), and/or p63

An optimal immunohistochemical panel to distinguish poorly differentiated prostate (PCa) from urothelial (UCa) carcinoma was selected from a panel consisting of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), high-molecular-weight cytokeratin (HMWCK), clone 34betaE12, cytokeratin (CK) 7, CK20, p63, and alpha-methylacyl-coenzyme A racemase. The pilot group was composed of poorly differentiated UCa (n = 36) and PCa (n = 42). PSA and PAP stained 95% of PCa vs 0% and 11% of UCa cases, respectively. HMWCK and p63 stained 97% and 92% of UCa vs 2% and 0% of PCa cases respectively. CK7/CK20 coexpression was noted in 50% of UCa cases, whereas 86% of PCa cases were negative with both. A panel of PSA, HMWCK, and p63 was optimal for separating 95% PCa (PSA+/HMWCK and/or p63-) vs 97% UCa (PSA-/HMWCK and/or p63+). This panel was used on 26 diagnostically challenging cases and resolved 81% of cases as UCa vs PCa. The majority of PCa cases retain PSA. Negative PSA with positive HMWCK and/or p63 establishes a diagnosis of UCa.

Prostate-Specific Antigen, High-Molecular-Weight Cytokeratin (Clone 34βE12), and/or p63

An optimal immunohistochemical panel to distinguish poorly differentiated prostate (PCa) from urothelial (UCa) carcinoma was selected from a panel consisting of prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP), high-molecular-weight cytokeratin (HMWCK), clone 34betaE12, cytokeratin (CK) 7, CK20, p63, and alpha-methylacyl-coenzyme A racemase. The pilot group was composed of poorly differentiated UCa (n = 36) and PCa (n = 42). PSA and PAP stained 95% of PCa vs 0% and 11% of UCa cases, respectively. HMWCK and p63 stained 97% and 92% of UCa vs 2% and 0% of PCa cases respectively. CK7/CK20 coexpression was noted in 50% of UCa cases, whereas 86% of PCa cases were negative with both. A panel of PSA, HMWCK, and p63 was optimal for separating 95% PCa (PSA+/HMWCK and/or p63-) vs 97% UCa (PSA-/HMWCK and/or p63+). This panel was used on 26 diagnostically challenging cases and resolved 81% of cases as UCa vs PCa. The majority of PCa cases retain PSA. Negative PSA with positive HMWCK and/or p63 establishes a diagnosis of UCa.

Variations PSA Value in Patients Candidate to Biopsy of the Prostate

Subclinical infections of the prostate can increase the prostate-specific antigen (PSA) values in patients with normal digital rectal examination. This study aimed to evaluate the role of short-term antimicrobial therapy in reducing the PSA value in patients as candidates for transrectal biopsy. Fifty-eight patients with negative digital rectal examination and PSA values between 4 and 20 ng/mL were included in the study. Antibiotics were administered to all patients for 3 weeks, and the PSA was reassessed 10 days after the end of the treatment. Patients were subsequently submitted to prostate biopsy. A reduction in PSA was detected in 34 patients (59%). Mean percentage reduction was 32%. In only six patients (10%) did the PSA return to normal levels. Prostate biopsy revealed prostate cancer in 26 patients (45%). Prostate cancer was not detected in patients with PSA levels above 4 ng/mL. Prostate biopsy can be avoided only in a small number of patients showing the normalization of PSA levels after short-term antimicrobial therapy. These patients should be strictly monitored with frequent PSA determinations.

A Markov model for optimal intervals in prostate cancer screening programs in the era of individual baseline PSA values

4618 Background: Once a prostate cancer screening program using prostate-specific antigen (PSA) has been established and is operational, the issue of the re-screening interval for patients with prior negative PSA results comes into question. We approached this issue using a decision-analytic model in which participants were stratified by baseline PSA values. Methods: Based on an actual contemporary screening program, we established a Markov decision analytic model of prostate cancer screening with different re-screening interval strategies determined by individual baseline PSA levels. Cost-effectiveness analysis was performed to determine the incremental cost-effectiveness ratio (ICER; costs per quality-adjusted life years) for each strategy. Results: Re-screening strategies with biennial PSA testing in men with PSA levels ≤3.0 and ≤4.0 ng/ml are dominated by biennial screening in men with PSA ≤2.0 ng/ml, which is the most cost-effective strategy. ICERs for annual screening and biennial screening strategies in men with PSA ≤1.0 were US$25,220 and US$10,557, respectively, with respect to strategies with biennial screening in men with PSA ≤2.0 ng/ml. On sensitivity analyses, ICER for annual screening with respect to biennial screening in men with PSA ≤2.0 ng/ml will be larger under conditions with a lower biopsy participation rate in PSA-positive participants, or a lower cancer detection rate on biopsy. It was also observed that ICER for an annual screening strategy is larger in an initial age cohort of men in their 50’s and 70’s than in their 60’s. Conclusions: Our model shows that cut off of baseline PSA for annual PSA testing in prostate cancer mass screening should be determined as 0.0 to 2.0 ng/ml based on clinical and economical variables in view of the budget of each society. No significant financial relationships to disclose.

PROSTATE BIOPSY FOLLOWING A POSITIVE SCREEN IN THE PROSTATE, LUNG, COLORECTAL AND OVARIAN CANCER SCREENING TRIAL

The benefit of prostate specific antigen (PSA) and digital rectal examination (DRE) screening for prostate cancer is under evaluation in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Followup of positive screens in PLCO is done by subject personal physicians and it is outside of trial control. We describe the pattern of prostate biopsy in men with positive screens in PLCO. We examined all men with positive baseline PSA or DRE screens and men with positive post-baseline screens occurring by December 2000. Of 2,717 men with positive PSA (greater than 4 ng/ml) at baseline 41% and 64% underwent biopsy within 1 and 3 years, respectively. A screening PSA of 7 to 10 and greater than 10 ng/ml at baseline was associated with significantly higher biopsy rates (HR 1.9 and 2.6, respectively) compared to PSA 4 to 7 ng/ml. The 1,793 in men whom the first positive PSA was after baseline had a lower overall biopsy rate (50% within 3 years). Furthermore, PSA above 7 ng/ml were not associated with higher biopsy rates in this group. The 4,449 men with positive DRE screens and negative PSA had a 3-year biopsy rate of 27%. Men with positive DRE at diagnostic followup had a biopsy rate of around 90%. However, few men, even of those with positive DRE screens, had positive diagnostic DREs. : These biopsy rates following positive PSA and DRE screens are likely to be representative of national rates. These results suggest that PLCO is evaluating the effects of screening in a contemporary and robust manner.

Adenosquamous carcinoma of the prostate

Adenosquamous carcinoma of the prostate is an unusual histological variant of prostate cancer. The histogenesis of this tumor remains uncertain. The stimulus for the development of the squamous metaplastic cells had been thought to be related to hormone and/or radiation therapy. This report presents a case of adenosquamous carcinoma of the prostate with abscence of previous hormone or radiation therapy. The case showed negative prostate-specific antigen and high molecular weight cytokeratin staining of the adenocarcinoma component, and negative prostate-specific antigen and positive high molecular weight cytokeratin staining of the squamous cell carcinoma component. The adenocarcinoma component stained intraluminally with periodic acid schiff. The staining features and the distinct localizations of the components with intermingling, but no transition, are against the collision-type tumor theory and support the theory that the adenocarcinoma and squamous components arise de novo from pluripotent stem cells. The patient had a rapid downhill clinical course and died 3 weeks after the diagnosis was made.

EFFECTS OF SYSTEMATIC 12-CORE BIOPSY ON THE PERFORMANCE OF PERCENT FREE PROSTATE SPECIFIC ANTIGEN FOR PROSTATE CANCER DETECTION

The performance characteristics of percent free (f) prostate specific antigen (PSA) for differentiating between benign prostatic hyperplasia and prostate cancer were originally established using primarily sextant biopsy. We determined whether the addition of 6 laterally directed cores to the traditional sextant prostate biopsy affects the performance of percent fPSA. We retrospectively evaluated a cohort of 350 consecutive biopsies in men with negative digital rectal examinations and PSA between 4 and 10 ng/ml who underwent systematic 12 core biopsy (S12C) biopsy at Scott Department of Urology between March 1999 and January 2003. The effects of 6 additional, laterally directed biopsies on the sensitivity, specificity and area under the ROC curve for percent fPSA was evaluated in the 277 men in whom percent fPSA was measured. Cancers detected exclusively in the 6 laterally directed cores were associated with percent fPSA values similar to those in patients with a benign S12C biopsy. This resulted in a modest and yet predictable decrease in the sensitivity of percent fPSA at each biopsy threshold value without affecting specificity. There was a nonstatistically significant decrease in the area under the ROC curve with the addition of 6 laterally directed cores to sextant biopsy (medial sextant cores 0.66 vs S12C 0.60). The 12 core biopsy strategies have a higher cancer detection rate than sextant biopsies and they are gaining widespread acceptance. The addition of 6 laterally directed cores to traditional sextant biopsy may result in a modest decrease in the sensitivity of percent fPSA at each selected biopsy threshold without affecting specificity.

Expression of alpha-methylacyl-CoA racemase (P504S) in nephrogenic adenoma: a significant immunohistochemical pitfall compounding the differential diagnosis with prostatic adenocarcinoma.

Alpha-Methylacyl-CoA racemase (AMACR, P504S) has recently been shown to be a useful marker for the diagnosis of prostatic adenocarcinoma and a potential aid in its distinction from its many mimics, one of which is the benign lesion, nephrogenic adenoma (NA). The goal of this study was to assess the expression of AMACR in NA by immunohistochemistry, as well as other potentially useful markers, high-molecular-weight cytokeratin clone 34betaE12, p63, and prostate-specific antigen (PSA). AMACR was expressed in 4/4 NAs involving the prostatic urethra and underlying stroma, and in 3/16 NAs involving the bladder. The prostatic cases showed circumferential granular cytoplasmic AMACR expression of at least moderate intensity, in >75% of tubules in 3 cases and in <10% of tubules in the remaining case. The AMACR-positive cases in the bladder typically showed focal weak noncircumferential staining of the tubules and stronger staining of the cells lining the papillae. 34betaE12 staining was observed in 1/4 prostatic NAs and 4/16 bladder NAs, typically in a cytoplasmic pattern in a minority of cells. p63 and PSA were negative in all cases. Our data indicate that NA of the prostatic urethra commonly expresses AMACR and lacks basal cell-specific markers, making it not only a potential morphologic mimic of prostatic adenocarcinoma but also a significant immunohistochemical mimic as well. Awareness of NA as a significant pitfall in the diagnosis of prostatic adenocarcinoma and careful examination of hematoxylin and eosin-stained sections remains the key to the correct diagnosis, which can be supported by a negative PSA stain.

Did the rate of incidental prostate cancer change in the era of PSA testing? A retrospective study of 1127 patients

ObjectivesTo evaluate, in a retrospective study, the impact of routine prostate-specific antigen (PSA) testing on the rate of incidental prostate cancer in patients undergoing surgery for obstructive symptoms caused by presumed benign prostatic enlargement (BPE) and to investigate the indication of a routine biopsy before alternative treatment procedures for BPE. In the pre-PSA era, the diagnosis of incidental carcinoma was exclusively based on normal digital rectal examination (DRE) findings. MethodsSince January 1993, 2422 operations (2283 transurethral resection of the prostate, 139 retropubic adenoma enucleations) for BPE were performed at our institution. The preoperative DRE findings and PSA level were evaluated, and patients with any suspicion for cancer were excluded. The pathologic reports of all patients were reviewed. A diagnosis of incidental carcinoma of the prostate required histologic evidence of cancer and negative DRE findings and a PSA level within age-specific reference ranges preoperatively. ResultsOf 2422 patients, 1127 (46.5%) had both negative DRE findings and an age-specific PSA level and were evaluated for our study. Overall, prostate cancer was diagnosed by surgery in 314 (13%) of 2422 patients. The rate of incidental prostate cancer in patients with both negative age-specific PSA levels and negative DRE findings was 6.4% (72 of 1127). ConclusionsIn our series, the likelihood of detecting incidental prostate cancer by surgery was 6.4%. In the PSA era, the rate of incidental prostate cancer has been decreased by more than 50%. Today, the low rate of incidental carcinoma does not warrant routine histologic evaluation of the prostate if PSA testing and DRE are negative when alternative treatment modalities without tissue sampling are offered for the treatment of BPE.

Secondary Signet-Ring Cell Carcinoma of the Prostate

A 70-year-old man was referred in May 1990 for a left lower ureteral stone. Digital rectal examination demonstrated a moderately enlarged prostate with an irregular surface. Serum prostate specific antigen (PSA) was 6.6 ng./ ml. Ultrasound guided biopsy of the prostate aiming toward the hypoechoic lesion showed nodular hyperplasia. Three years previously the patient had undergone radical gastrectomy for signet-ring cell carcinoma of the stomach (stage pT3N2M0) followed by adjuvant chemotherapy. Followup computerized tomography and radioisotope bone scan revealed absence of tumor. The patient subsequently underwent transurethral resection of the prostate in February 1991 for increasing lower urinary tract symptoms and a PSA of 9.7 ng./ml. Pathological examination demonstrated poorly differentiated signet-ring cell carcinoma with negative PSA staining (figs. 1 and 2). Staging computerized tomography showed infiltrative tumor in a cul-de-sac with direct invasion of the prostate. The patient was managed conservatively. Nine months later he underwent exploratory laparotomy for intestinal obstruction. Generalized tumor seeding to the omentum and cul-de-sac was confirmed at that time.

Circulating prostate-specific antigen mRNA during radical prostatectomy in patients with localized prostate cancer: with special reference to neoadjuvant hormonal therapy.

To determine the potential risk of hematogenous dissemination of prostate cancer cells during radical prostatectomy (RP), we investigated the pre- and intraoperative circulating prostate-specific antigen (PSA) mRNA in patients with clinically localized prostate cancer, with special reference to neoadjuvant hormonal therapy (NHT). Using a nested reverse transcriptase (RT) polymerase reaction (PCR) assay, PSA mRNA in the peripheral blood was evaluated pre- and postoperatively in a total of 23 patients, 10 of whom received NHT with antiandrogens. The RT-PCR assay employed detected one LNCaP cell in 10(7) mononuclear blood cells, and showed no positive signal in the blood samples from all 15 healthy controls. Pre- and intraoperative circulating PSA mRNA was positive in 11 (48%) and 18 patients (78%), respectively. All 11 patients with positive preoperative PSA mRNA continued to be positive during RP, and seven (58%) of 12 patients with negative preoperative PSA mRNA had a positive conversion. Although the patients' ages, preoperative serum PSA values and clinical or pathological stages were not associated with the pre- and intraoperative PSA mRNA results, the NHT group showed a significantly lower incidence of preoperative PSA mRNA positivity (2/10) than the group receiving RP alone (9/13) (20% vs 69%, P = 0.036). NHT, however, showed no suppressive effect on either intraoperative positivity or positive conversion of circulating PSA mRNA. The present study suggests that a substantial number of patients receiving RP are at risk of hematogenous dissemination, and NHT with antiandrogens has a minimal or no suppressive effect on the circulating PSA mRNA during surgical manipulation of the prostate. Because the clinical significance of circulating cancer cells remains to be determined, long-term follow-up in association with the circulating cancer cells assessed by the RT-PCR is essential in order to establish the role of molecular staging as well as NHT.

Effect of prostate biopsy on the results of the PSA RT-PCR test

Objectives. To evaluate the effect of prostate biopsy on the prostate-specific antigen (PSA) reverse transcriptase-polymerase chain reaction (RT-PCR) test. Methods. Ninety men who were scheduled to undergo prostate biopsy because of an elevated PSA or abnormal digital rectal examination, or both, were recruited to have PSA RT-PCR performed on peripheral blood samples drawn before and at 30 minutes, 1 week, and 1 month after undergoing prostate biopsy. PSA RT-PCR was performed and all PCR products were blotted and hybridized with phosphorus-32 ( 32-P)-PSA cDNA probe (exon 3 to 5). Results. Of 90 patients, 77 had a negative prebiopsy PSA RT-PCR result. Of these 77, 2 (2.6%) had a positive PSA RT-PCR result at some point after the biopsy procedure. Both of these patients had no evidence of malignancy on biopsy. The PSA RT-PCR test was positive at 30 minutes for 1 patient, but was negative at 1 week; the other was positive at 1 week but the patient did not return for the 1-month sample. Conclusions. Our study indicates that 2.6% of patients with an initially negative PSA RT-PCR will have a positive PSA RT-PCR test after biopsy has been performed. Although this is uncommon, it may have profound implications for those patients in whom it occurs. On the basis of our results, it appears that one should wait longer than 1 week after prostate biopsy before obtaining blood for PSA RT-PCR testing to decrease the likelihood of a spurious PSA RT-PCR result.

PRELIMINARY OUTCOMES FOLLOWING CRYOSURGICAL ABLATION OF THE PROSTATE IN PATIENTS WITH CLINICALLY LOCALIZED PROSTATE CARCINOMA

Purpose Cryosurgical ablation of the prostate is a novel therapeutic modality that induces cell lysis in the prostate by direct application of low temperatures. We have been conducting an ongoing prospective pilot study of the use of cryosurgical prostate ablation in treating patients with nonmetastatic prostate adenocarcinoma since January 1993. Results in 145 consecutive patients with mean 36 months and minimum 12 months of followup are presented. Materials and Methods Accrual was open to patients with clinical stages T1a to T3c prostate adenocarcinoma. Pelvic lymph node dissections were recommended but not required for patients with prostate specific antigen (PSA) greater than 15 ng./ml. before study entry. PSA changes, random prostate biopsy findings and morbidities after cryosurgical prostate ablation were recorded for each patient. Results Overall actuarial rates at 42 months for maintaining PSA less than 0.3 and less than 1.0 were 59% and 66%, respectively. The overall actuarial progression-free rate at 60 months was 56%. Among 160 biopsies performed 16% showed some evidence of residual carcinoma. Overall crude rates of maintaining either a negative biopsy or PSA less than 0.3 at 6 and 24 months after cryosurgical prostate ablation were 87% and 73%, respectively. Significantly higher morbidities were seen in previously radiated patients undergoing cryosurgical prostate ablation compared to those with no prior radiation. Among nonradiated patients 85% experienced no significant morbidity after cryosurgical prostate ablation. Conclusions Although preliminary, short-term outcomes after cryosurgical prostate ablation appear to be comparable to identical outcomes reported for external beam radiotherapy. Based on these results cryosurgical prostate ablation appears to be an effective therapeutic alternative for treating patients with localized prostate adenocarcinoma.

Presence of circulating prostate cells in the bone marrow of patients undergoing radical prostatectomy is predictive of disease-free survival.

To determine whether the presence of circulating prostate cells in the bone marrow is associated with disease-free survival in patients undergoing radical prostatectomy. We evaluated the bone marrow of 86 patients with clinically localized prostate cancer treated by radical prostatectomy for the presence of circulating prostate cells using reverse-transcriptase polymerase chain reaction (RT-PCR) amplification of prostate-specific antigen (PSA) mRNA. Follow-up duration ranged from 1 to 43 months (mean, 15.4). Two of 47 patients (4%) with negative RT-PCR PSA results and 10 of 39 patients (26%) with positive RT-PCR PSA results have had disease recurrence. Patients whose RT-PCR PSA results were positive had a significantly shorter disease-free survival period than those patients with negative RT-PCR PSA results (P = .004). RT-PCR status correlated significantly with serum PSA level (P = .001) and pathologic stage (P = .003). Based on Cox's proportional hazards models, RT-PCR status was found to be a significant predictor of disease-free survival. However, after controlling for PSA level, RT-PCR status was not significant in predicting disease-free survival. RT-PCR PSA of bone marrow may be a useful pretreatment prognostic test for patients undergoing radical prostatectomy. Currently, this test should not be used to determine if patients receive definitive local therapy.

Evaluation of prostate specific antigen density and transrectal ultrasonography-guided biopsies in 100 consecutive patients with a negative digital rectal examination and intermediate serum prostate specific antigen levels.

This study was undertaken to assess the importance of prostate biopsies in patients with a negative digital rectal examination (DRE) and elevated prostate specific antigen (PSA) levels and to investigate the role of PSA density (PSAD) and hypoechoic lesions on transrectal ultrasound (TRUS) in increasing the diagnostic sensitivity and specificity for prostate cancer (PCa). One hundred patients with varied initial symptoms who had a negative DRE and a PSA level between 4 and 20 ng/mL underwent TRUS-guided systematic and, if present, lesion-directed biopsies. PCa was detected in 11 patients (11%). TRUS examinations revealed hypoechoic lesions in 31 patients. Lesion-directed biopsies revealed PCa in 13% (4/31) of patients with abnormal TRUS whereas, 7% (5/69) of patients with negative TRUS findings had PCa. Additional systematic biopsies detected PCa in 2 patients where lesion-directed biopsies were negative. None (0/19) of the lesions smaller than 0.2 mL on TRUS had PCa whereas, 33% (4/12) of patients with lesions greater than 0.2 mL had PCa. When the subgroup of patients with negative TRUS and PSA levels between 4 and 10 ng/mL were considered, 25% (1/4) of cases with PCa would have been missed if 0.15 was used as the cut-off point for PSAD, however, this would save 61% (30/49) of unnecessary biopsies. The positive predictive value of PSA (cut-off level 10 ng/mL), PSAD (cut-off level 0.15), and hypoechoic lesions on TRUS were found to be 11.5%, 33%, and 13%, respectively. When hypoechoic lesions greater than 0.2 mL were taken as the positive finding, the positive predictive value and specificity rates of TRUS increased to 33% and 91%, respectively, without any change in the sensitivity. In patients with a negative DRE and intermediate PSA levels, the application of PSAD would have saved 49% of study patients with BPH from a biopsy, but would have missed 27% of PCa cases. By ignoring lesions smaller than 0.2 mL on TRUS, a very high specificity of 91% was achieved with a sensitivity of 36%. Thus, further investigations aimed at defining a better mode of diagnosis of PCa are warranted.

A pilot study of mass screening program for prostatic cancer by means of prostate specific antigen (PSA) filter paper method

Mass screening program for prostatic cancer (PC) using prostate specific antigen (PSA) filter paper method was performed in an urban area of Kyoto in 1995. In the primary study, males more than the age of 55 years were examined by PSA (Delfia PSA kit) with blood samples on a filter paper. The cut-off values were set at 4 and 10 ng/ ml. Subjects whose PSA level ranged from 4.1 to 10.0 ng/ml (gray zone) were examined by digital rectal examination (DRE), transrectal sonography (TRS) and PSA density (PSAD; more than 0.15) in the secondary study, then the suspected subjects of PC underwent 6 sextant biopsies under interventional ultrasound. Subjects whose PSA level were more than 10.1 ng/ml were biopsied directly. Of 3,749 males who took the annual health checkup system organized by the government, 2,387 males wished to submit this screening. Among them, 2,217 (92.9%) showed a negative PSA, 107 belonged to the gray zone and 43 had a PSA more than 10.1 ng/ml. Of these, 102 subjects underwent biopsy. PC was finally detected in 28 (1.2%). The positive predictive value for positive PSA and gray zone PSA was 46.3% and 8.4%, respectively. In the detected cancers, 17 cases (60.7%) belonged to Stage B, 5 (17.9%) to Stage C and 6 (21.4%) to Stage D. The results suggested that this system of mass screening program for PC combined with the annual health checkup was suitable for the future "national-level" screening.