Can Free and Total Prostate Specific Antigen and Prostatic Volume Distinguish Between Men With Negative and Positive Systematic Ultrasound Guided Prostate Biopsies?

Purpose

We evaluated the role of free and total serum prostate specific antigen (PSA) and prostate volume in discriminating between men with negative and positive transrectal ultrasound guided biopsies.

Materials and Methods

A total of 104 consecutive men with a positive biopsy and at least 3 mm. of prostate cancer was compared to 110 consecutive men with a negative biopsy. Prostate volume was determined by transrectal ultrasound. Total PSA was determined by the Tosoh AIA-600† PSA assay and free PSA was measured by the PSA II Dianon‡ assay. We determined the free-to-total PSA ratio, free and total PSA densities, and the relationship of free PSA and free-to-total PSA ratio to prostate volume.

Results

Using a 23% cutoff value of free-to-total PSA, only 22.7% of biopsies were preventable in patients with a negative biopsy but 9.6% of the cancers were missed. At a total PSA of 4 to 10 ng./ml. 44.4% of the biopsy negative cases were correctly identified while missing 9.1% of the cancers if a 20% free PSA cutoff is used. For total PSA more than 10 ng./ml. an 18% free PSA cutoff properly identified 30.2% of the biopsy negative cases while missing 9.3% of the cancers. Percent free PSA is a better discriminant than prostate volume for total PSA more than 4 ng./ml. and the combination was not helpful. Free PSA density was identical in patients with negative and positive biopsies. There was no relationship between free PSA or free-to-total PSA ratio levels and prostate volume.

Conclusions

Use of a single discriminant criterion of free-to-total PSA ratio in the practical clinical setting of distinguishing negative and positive biopsies appears useful in patients with a total PSA of 4 to 10 ng./ml. Since free PSA is unrelated to prostate volume in biopsy negative and positive cases the physiological basis of free PSA is an enigma.     

Prospective Evaluation of Prostate Specific Antigen and Prostate Specific Antigen Density in the Detection of Nonpalpable and Stage T1C Carcinoma of the Prostate

Purpose

We evaluated prospectively prostate specific antigen (PSA) and prostate specific antigen density in the detection of prostate cancer in patients with normal findings on digital rectal examination with and without normal transrectal ultrasound.

Materials and Methods

Consecutive patients (184) with an elevated serum PSA and normal digital rectal examination underwent transrectal ultrasound with lesion directed and systematic biopsies (6 if prostatic volume was 50 cc or less and 12 if volume was more than 50 cc). Receiver operating characteristic curves, predictive values and likelihood ratios were calculated for PSA and PSA density.

Results

Of the 184 patients 50 (27 percent) with a normal digital rectal examination had cancer compared to 30 of 112 (27 percent) with a normal digital rectal examination and transrectal ultrasound. Median PSA or PSA density did not differ between the positive and negative biopsy groups among patients with a normal digital rectal examination (8.4 versus 7.1 and 0.22 versus 0.14 ng./ml., respectively) or a normal digital rectal examination and transrectal ultrasound (8.2 versus 7.5 and 0.21 versus 0.14 ng./ml., respectively). PSA density was superior to PSA by receiver operating characteristic analysis for cancer detection when all PSA values or those between 4 and 20 ng./ml. were considered. However, the significance was lost for a PSA of 4 to 10 ng./ml. Likelihood ratios demonstrated insignificant changes in the post-test probability if PSA density was used to determine the need for biopsy and many cancers would have been missed.

Conclusions

PSA density should not be used to determine the need for biopsy in patients with a normal digital rectal examination and/or transrectal ultrasound.     

The Free-To-Total Prostate Specific Antigen Ratio Improves the Specificity of Prostate Specific Antigen in Screening for Prostate Cancer in the General Population

Purpose

The ratio between free and total prostate specific antigen (PSA) in serum improves the specificity of total serum PSA for the detection of prostate carcinoma in select populations. The value of the free-to-total PSA ratio for a PSA of 4.0 to 10.0 ng./ml. was analyzed in a screening population.

Materials and Methods

From 4,800 participants 55 to 76 years old 977 biopsies were obtained because of an abnormal digital rectal examination, suspicious transrectal ultrasonography and total serum PSA 4.0 ng./ml. or more. Of 191 patients with prostate carcinoma detected 101 had a serum PSA of 4.0 to 10.0 ng./ml. and 54 of them underwent radical prostatectomy. A free-to-total PSA ratio of 0.20, age specific PSA reference ranges and a PSA density of 0.12 ng./ml./cc were evaluated for the ability to increase the specificity of total serum PSA in predicting positive prostate biopsy results.

Results

Receiver operating characteristics curves for the free-to-total PSA ratio showed a significant increase in specificity compared to PSA. Retrospective application of age specific PSA reference ranges, the free-to-total PSA ratio and the PSA density decreased the number of biopsies significantly by up to 40% in our study, with a decrease in cancer detection rate of 12%. When used in combination with digital rectal examination, the pathological stage of undetected carcinomas appeared favorable.

Conclusions

The free-to-total PSA ratio may be used to decrease biopsies in patients with an intermediate PSA of 4.0 to 10.0 ng./ml.     

CHARACTERISTICS OF SCREENING DETECTED PROSTATE CANCER IN MEN 50 TO 66 YEARS OLD WITH 3 TO 4 NG./ML. PROSTATE SPECIFIC ANTIGEN

Purpose

We defined the yield and nature of prostate cancer in the setting of population based, randomized prostate specific antigen (PSA) guided screening in men with PSA levels between 3 and 4 ng./ml. who were 50 to 65 years old at the time of randomization.

Materials and Methods

Sextant biopsies were performed in 243 men with PSA of 3 to 4 ng./ml. Therapy decisions were based on core cancer length, histological grade and life expectancy.

Results

Of the men 32 (13.2%) had prostate cancer constituting 23% of all of the 137 prostate cancers to date detected in the first round of our screening study. Age and PSA were similar in men with and without prostate cancer. Men with prostate cancer had significantly lower free PSA and free-to-total PSA ratio, and higher PSA density. Cancer was clinical stage T1c in 27 cases and stage T2 in 5. Hypoechoic areas were noted at transrectal ultrasound in 10 cases. Digital rectal examination and transrectal ultrasound were normal in 21 cases (66%). To date 14 patients have undergone prostatectomy. Surgical specimens showed a mean tumor volume of 1.8 cc (range 0.6 to 4.4) and significant amounts of high grade tumor were present in only 3 cases. Margins were positive in 5 cases, and pathological stage was pT2 in 8 cases and pT3 in 6.

Conclusions

By lowering the PSA cutoff from 4 to 3 ng./ml. an increase in cancer detection by 30% was achieved. While the addition of free-to-total ratio and PSA density may reduce the number of biopsies by about 15% with sensitivity maintained at 90%, systematic sextant biopsies were necessary in most of these men as 66% of the tumors were negative on transrectal ultrasound and digital rectal examination. The majority of these cancers were clinically significant and suitable for curative treatment. If therapy decisions are based on the pathological findings of the biopsies, the risk of treating insignificant cancers seems low.     

Prostate Specific Antigen Density Versus Prostate Specific Antigen Slope as Predictors of Prostate Cancer in Men with Initially Negative Prostatic Biopsies

Purpose

We determined if prostate specific antigen (PSA) density and PSA slope alone or in combination could be used to predict which men with persistently elevated serum PSA and prior negative prostate biopsies will have prostate cancer on repeat evaluation.

Materials and Methods

In our PSA-1 data base we identified 327 men 50 years old or older with an initially negative prostate biopsy who had persistent PSA elevation, and compared those who did and did not have prostate cancer on subsequent serial prostatic biopsy.

Results

Of 70 men with a PSA density of 0.15 or more and PSA slope of 0.75 ng./ml. or more annually compared to 83 with a PSA density of less than 0.15 and PSA slope of less than 0.75 ng./ml. annually 32 (46 percent) and only 11 (13 percent), respectively, had prostate cancer on subsequent prostate biopsies (p less than 0.0001). In a hierarchical logistic regression analysis PSA density and PSA slope were predictive of prostate cancer on subsequent biopsy (p = 0.001 and 0.03, respectively). PSA density of 0.15 or more alone or PSA slope of 0.75 ng./ml. or more annually alone as the indicator for repeat biopsy would have missed 35 and 40 percent of cancers, respectively.

Conclusions

In men with persistently elevated serum PSA after an initially negative prostate biopsy, PSA density and PSA slope alone or in combination provide useful predictive information about the results of repeat prostate biopsies. However, these parameters are not sufficiently sensitive to identify all patients with detectable prostate cancer.     

SERUM FREE PROSTATE SPECIFIC ANTIGEN AND PROSTATE SPECIFIC ANTIGEN DENSITY MEASUREMENTS FOR PREDICTING CANCER IN MEN WITH PRIOR NEGATIVE PROSTATIC BIOPSIES

Purpose

We examined the usefulness of measurements of free prostate specific antigen (PSA) and PSA density for predicting prostate cancer in men who had had a prior negative biopsy, a serum PSA level of 4.1 to 10.0 ng./ml. and benign findings on prostate examination.

Materials and Methods

We measured percent free serum PSA and PSA density in 163 male volunteers age 50 years or older who were advised to have repeat prostatic biopsies for a serum PSA level of 4.1 to 10.0 ng./ml.

Results

Of 99 men who had repeat biopsies 20 (20%) had prostate cancer detected. Prostate cancer was significantly associated with lower free PSA level and higher PSA density, with overlap in 83% of the cases. The use of percent free PSA cutoffs of 28 and 30% would have detected 90 and 95% of cancers, respectively, and avoided 13 and 12% of the biopsies, respectively. PSA density cutoffs of 0.10 and 0.08 would have detected 90 and 95% of cancers, respectively, and avoided 31 and 12% of biopsies, respectively.

Conclusions

Free PSA and PSA density predict prostate cancer in men who have had prior negative prostatic biopsies, serum PSA levels of 4.1 to 10.0 ng./ml. and a benign prostate examination. Both parameters may be used to avoid unnecessary biopsies with an acceptable decrease in sensitivity. Further studies are needed to determine cutoffs to be used in clinical practice.     

Cancer Diagnosis with Prostate Specific Antigen Greater than 10 ng./ml. and Negative Peripheral Zone Prostate Biopsy

Purpose

We assessed the results of additional diagnostic procedures in men with prostate specific antigen (PSA) more than 10 ng./ml. and a peripheral zone prostate biopsy negative for cancer.

Materials and Methods

A total of 68 men with PSA more than 10 ng./ml. and a peripheral zone biopsy negative for cancer was investigated with 1 or more peripheral zone biopsies (17), prostatectomy (18), or 1 or more peripheral zone biopsies and needle biopsy of the transition zone or prostatectomy (33).

Results

Cancer was detected in 20 of 68 patients (29 percent) with 1 or more additional diagnostic procedures. Of 51 patients whose transition zone was biopsied or who underwent prostatectomy 16 had cancer, and in 8 the malignancy appeared to be isolated to the transition zone. Mean PSA density and proportion of patients with PSA density more 0.15 were significantly greater and mean prostate volume was significantly less in the 20 patients with compared to 31 without identifiable cancer.

Conclusions

At least 30 percent of men with PSA more than 10 ng./ml. and a negative peripheral zone biopsy have prostate cancer. In approximately 50 percent of cases the cancer appears to reside in the transition zone, and transition zone biopsy or prostatectomy is required for diagnosis.     

CRYOSURGICAL ABLATION OF PROSTATE CANCER: PATTERNS OF CANCER RECURRENCE

Purpose

We determined the rate of biochemical and biopsy failure in relation to the prostate specific antigen (PSA) nadir, the effect of neoadjuvant androgen blockade and the pattern of residual tumor after cryosurgical ablation of prostate cancer.

Materials and Methods

From July 1993 to April 1996, 134 patients underwent 147 cryosurgical ablation procedures. Of those patients, 110 had adequate followup and did not receive post-treatment androgen deprivation. Followup included PSA determination at 3, 6 and 12 months, and every 6 months thereafter. Biopsies were performed at 6 months or with biochemical failure defined as PSA nadir 0.5 ng./ml. or greater or subsequent biochemical failure (PSA increase 0.2 ng./ml. or greater). Biochemical and biopsy failures were correlated with PSA nadir values following cryosurgery (less than 0.1 ng./ml., 0.1 to 0.4 and or greater 0.5). A total of 68 patients had careful ultrasound guided mapping biopsy preoperatively and postoperatively to define the sites of disease. The likelihood of residual disease was correlated with the initial site(s) of the cancer in an attempt to identify if areas of the prostate and/or seminal vesicles were more likely to be sites of treatment failure.

Results

At a mean followup of 17.6 months biochemical failure (subsequent rise in PSA 0.2 ng./ml. or greater) was lowest in those who achieved PSA nadirs less than 0.1 ng./ml. (21%) but it was noted in 48% of patients with nadirs between 0.1 and 0.4 ng./ml. Those patients with PSA nadirs 0.5 or greater had either immediate local failure (46%), subsequent local or biochemical failures (43%) or extremely high PSA nadirs (greater than 30 ng./ml.) necessitating hormonal therapy (11%). Biopsy failure was lowest in those with nadirs less than 0.1 ng./ml. (7%) and those with nadirs 0.1 to 0.4 ng./ml. (22%). In contrast, 60% of the patients with nadir values 0.5 ng./ml. or greater had biopsy failure. Biochemical and biopsy failure tended to occur within the first 18 months after treatment. Neoadjuvant androgen blockade appeared to reduce subsequent biochemical failure in patients with stages T1 and T2 cancers (11% versus 50% in those without androgen deprivation) but not in those with T3 and T4 cancers. Recurrence was more common in cancers at the apex (9.5%) and seminal vesicles (44%), in contrast to those located in the mid gland (4%) and base (0%).

Conclusions

A PSA nadir of 0.4 ng./ml. or less should be achieved following cryotherapy. Higher values are associated with a significant risk of continued PSA elevation and a high likelihood of residual disease detected on prostatic biopsy. Local failure tends to occur at the apex and seminal vesicles. Neoadjuvant androgen blockade reduces the risk of biochemical failure in patients with stages T1 and T2 cancers.     

Strategy for Repeat Biopsy of Patients with Prostatic Intraepithelial Neoplasia Detected by Prostate Needle Biopsy

Purpose

We evaluated the strategy for repeat biopsy of patients with prostatic intraepithelial neoplasia without concurrent carcinoma detected on prostate needle biopsy.

Materials and Methods

Of 1,275 consecutive patients undergoing prostate needle biopsy 61 were identified with prostatic intraepithelial neoplasia but without concurrent prostate carcinoma. Of the 61 patients 53 had undergone repeat biopsy. The medical records, transrectal ultrasound, and operative and pathological reports of these patients were reviewed.

Results

Repeat biopsy was done in 53 patients with prostatic intraepithelial neoplasia, yielding carcinoma in 15, prostatic intraepithelial neoplasia without carcinoma in 8 and benign tissue in 30. The yield of carcinoma from repeat biopsy of a prostatic intraepithelial neoplasia site was 8.3 percent (7 of 84 sites). A total of 18 sites of carcinoma was detected by repeat biopsy of a previous random biopsy site (8), a prostatic intraepithelial neoplasia site only (5), a transrectal ultrasound nodule (3), a palpable nodule and prostatic intraepithelial neoplasia site (1), and a transrectal ultrasound nodule and prostatic intraepithelial neoplasia site (1). Carcinoma was as frequently detected by repeat biopsy of a prostatic intraepithelial neoplasia site (6 patients) as by random repeat biopsy (6 patients).

Conclusions

Repeat prostate needle biopsy of patients with prostatic intraepithelial neoplasia should include random repeat biopsy and repeat biopsy of transrectal ultrasound abnormalities as well as previous sites of prostatic intraepithelial neoplasia.     

Systematic 5 Region Prostate Biopsy is Superior to Sextant Method for Diagnosing Carcinoma of the Prostate

Purpose

The number of patients undergoing prostate biopsy has dramatically increased due to prostate specific antigen screening. The low specificity of this screening tool requires prostate biopsy for diagnosis of prostate cancer. The sextant biopsy technique has been used widely with success in diagnosing carcinoma of the prostate. However, concern has arisen that the original sextant method may not include an adequate sampling of the prostate. For many years we have used a method of prostate biopsy that, in addition to sextant biopsies, takes additional biopsies in a systematic fashion, which we call the 5 region prostate biopsy. We conducted a prospective study to determine if our 5 region prostate biopsy technique significantly increases the chances of finding carcinoma of the prostate compared to the sextant biopsy technique.

Materials and Methods

A total of 119 patients underwent transrectal ultrasound guided needle biopsy of the prostate. In addition to sextant biopsies, cores were taken from the far lateral and mid regions of the gland. Pathological findings of the additional regions were compared to those of the sextant regions.

Results

Of the 48 patients with prostate cancer 17 (35%) had carcinomas only in the additional regions, which would have remained undetected had the sextant biopsy technique been used alone (p <0.05). Of these additional cancers 83% had Gleason scores of 6 or more.

Conclusions

We introduce the 5 region technique of prostate biopsy as a means of significantly increasing the diagnostic yield of prostate biopsy in finding carcinoma of the prostate. We have found this technique to be safe, efficacious and superior to the sextant method of biopsy in identifying prostate cancer at an early but significant stage. The greatest use of the 5 region biopsy technique is in patients who have prostate specific antigen levels between 4 and 10 ng./ml.     

Prostate Specific Antigen Density of the Transition Zone: A New Effective Parameter for Prostate Cancer Prediction

Purpose

Use of prostate specific antigen (PSA) density to enhance the predictive value of detecting prostate cancer at intermediate PSA levels has been limited due to contradictory results in large scale studies. Most PSA leakage from the benign prostate into the serum comes from the transition zone. Therefore, in patients with benign prostatic hyperplasia (BPH) and prostate cancer with a serum PSA of less than 10 ng./ml. we studied and compared the values of PSA density of the total prostate and the transition zone. We examined the ability of PSA density of the transition zone to enhance prostate cancer detection in patients with intermediate PSA levels.

Materials and Methods

The volumes of the entire prostate and of the transition zone were determined by transrectal ultrasound. PSA density for both regions was calculated in 88 patients with histologically confirmed prostate cancer (radical prostatectomy), and 74 with BPH and histologically proved benign disease.

Results

Average total prostate PSA density plus or minus standard deviation was 0.12 +/− 0.07 and 0.22 +/− 0.12 ng./ml./cc in patients with BPH and prostate cancer, respectively, while average PSA density of the transition zone was 0.21 +/− 0.13 and 1.02 +/− 0.70 ng./ml./cc, respectively (p <0.0001). If a total prostate PSA density of 0.15 had been chosen, the cancer would have been missed in 34% of the patients compared to 10% if a cutoff value of 0.35 for PSA density of the transition zone had been chosen (p <0.001). Overall, in patients with a PSA of 0.25 to 10.0 ng./ml. the sensitivity and specificity of PSA density of the transition zone for predicting prostate cancer at a 0.35 cutoff value were 90 and 93%, respectively, compared to 94 and 89%, respectively, for those with a PSA of 4 to 10 ng./ml.

Conclusions

In our study PSA density of the transition zone was much more accurate in predicting prostate cancer than was total prostate PSA density for PSA levels of less than 10 ng./ml. With respect to the high sensitivity and specificity, if confirmed in large prospective studies, including patients seen for early diagnosis, PSA density of the transition zone could become a routine tool for urologists in the prediction of prostate cancer in men with a PSA of 4 to 10 ng./ml.     

Treatment of chronic prostatitis lowers serum prostate specific antigen

PURPOSE: We evaluated men with documented chronic prostatitis and elevated serum prostate specific antigen (PSA) to determine whether treatment with antibiotics and anti-inflammatory drugs lowers serum PSA. MATERIALS AND METHODS: We retrospectively reviewed the records of 95 men who presented with serum PSA greater than 4 ng./ml. and were subsequently diagnosed with chronic prostatitis with greater than 10 white blood cells per high power field in expressed prostatic excretions. Patients meeting these criteria were treated with a 4-week course of antibiotics and a nonsteroidal anti-inflammatory agent. In all patients followup PSA was determined within 2 months of treatment. RESULTS: Mean PSA decreased 36.4% from 8.48 ng./ml. before to 5.39 after treatment (p <0.001). In 44 patients (46.3%) serum PSA decreased to below 4 ng./ml. (mean 2.48) and these patients no longer had an indication for biopsy. In the remaining 51 patients serum PSA remained elevated at greater than 4 ng./ml. and they underwent double sextant transrectal ultrasound guided biopsy. Pathological study showed prostate cancer in 13 cases (25.5%), chronic inflammation in 37 (72.5%) and only benign prostatic hypertrophy in 1 (1.05%). PSA in the 13 patients with prostate cancer decreased with treatment only 4.8% from 8.32 to 7.92 ng./ml. (p >0.05). Followup PSA at a mean of 11.4 months was determined in 19 of the 44 men who responded to treatment. Mean PSA increased only 4.5% from 2.35 to 2.46 ng./ml. (p >0.05) during this followup interval. CONCLUSIONS: In almost half of the patients diagnosed with elevated PSA and chronic prostatitis serum PSA normalized with treatment and there was no longer an indication for transrectal ultrasound guided biopsy. Our study suggests that chronic prostatitis is an important cause of elevated PSA and when it is identified, treatment can decrease the percent of negative biopsies.     

PREDICTIVE VALUE OF PROSTATE SPECIFIC ANTIGEN NADIR AFTER SALVAGE CRYOTHERAPY

Purpose

We determined nadir prostate specific antigen (PSA) after salvage cyrotherapy to distinguish patients who are potentially cured from those at risk for subsequent biochemical and biopsy proved failure.

Materials and Methods

A total of 146 patients who underwent salvage cyrotherapy were followed a median of 21 months (range 3 to 47) with regular serum PSA analysis and digital rectal examination. Sextant biopsies were performed at 6 months or earlier when PSA increased greater than 2 ng./ml. from the nadir value (biochemical failure) or there was a palpable local recurrence. We compared the incidence of biochemical failure and biopsy specimens positive for cancer to pretreatment PSA and posttreatment nadir PSA.

Results

In 59 of the 146 patients (40%) PSA decreased to an undetectable level within a median of 3 months. In 85 of the 109 patients (78%) who underwent biopsy the specimens were negative for cancer. Low serum PSA nadir values were associated with low pretreatment PSA and a low incidence of biochemical failure. In 6 of 60 patients (10%) in whom PSA nadir was 0.5 ng./ml. or less and in 18 of 49 (37%) with a higher PSA nadir biopsy was positive for cancer.

Conclusions

A PSA nadir of 0.5 ng./ml. or less should be achieved after salvage cryotherapy. Higher nadirs are more likely to be associated with increasing posttreatment PSA and positive biopsies. PSA nadir is a better prognostic indicator of biochemical and biopsy proved failure after salvage cryotherapy than pretreatment PSA.     

AGE SPECIFIC PROSTATE SPECIFIC ANTIGEN REFERENCE RANGES: POPULATION SPECIFIC

Purpose

We determined whether 60 to 79-year-old men with a negative digital rectal examination and a serum prostate specific antigen (PSA) within age specific PSA reference ranges could safely forgo prostate biopsy.

Materials and Methods

We reviewed the medical records of all 60 to 79-year-old men at the Brooklyn Veterans Administration Medical Center who had a PSA assay, digital rectal examination and subsequent prostate biopsy for an abnormal rectal examination and/or PSA greater than 4.0 ng./ml. from January 1991 through August 1995. We compared our results using the standard reference range of 0 to 4.0 ng./ml. with those obtained had we used any of 4 different age specific PSA reference ranges.

Results

We performed 1,280 prostate biopsies in 1,046 men with available PSA and digital rectal examination data. Using age specific PSA reference ranges 73 of 1,280 biopsies (5.7%) would have been avoided. Of those 73 avoided biopsies 15 (20.5%) had cancer that would have gone undetected and 9 of 15 (60%) undetected cancers had unfavorable histology. Results were not statistically significantly different among the 4 age specific PSA reference ranges. Regarding race, cancer detection rates were significantly higher for black compared with white men but there was no statistically significant difference for missed cancers or missed cancers with unfavorable histology.

Conclusions

In contrast to previous reports of unfavorable histological characteristics in only 5% of missed cancers using age specific PSA reference ranges, 60% of missed cancers in our patients exhibited unfavorable histology. We conclude that age specific PSA reference ranges did not safely eliminate the need for prostate biopsy in our study population. In 60 to 79-year-old men with a negative digital rectal examination we continue to use PSA greater than 4.0 ng./ml. as an indication for prostate biopsy.     

Prostatic Intraepithelial Neoplasia: Influence of Clinical and Pathological Data on the Detection of Prostate Cancer

Purpose

We attempted to characterize patients diagnosed with prostatic intraepithelial neoplasia without concurrent cancer on biopsy who had prostate cancer on subsequent biopsy.

Materials and Methods

The records of 93 patients with low and high grade prostatic intraepithelial neoplasia without concurrent cancer on initial biopsy were analyzed. The relationships among prostatic intraepithelial neoplasia grades, patient age, digital rectal examination, serum prostate specific antigen (PSA), transrectal ultrasound appearance and final pathological results were investigated.

Results

Subsequent carcinoma was found on repeat biopsy in 13.3 percent of patients with low grade and 47.9 percent with high grade prostatic intraepithelial neoplasia (p less than 0.001). In the former group digital rectal examination, patient age, serum PSA and transrectal ultrasound were not predictive of cancer. Transrectal ultrasound appearance, digital rectal examination and serum PSA were statistically different between high grade prostatic intraepithelial neoplasia with and without subsequent cancer (p less than 0.001, p = 0.008 and p = 0.016, respectively, univariate analysis). On multivariate analysis of patients with high grade prostatic intraepithelial neoplasia only digital rectal examination and PSA were predictive of subsequent carcinoma.

Conclusions

High grade prostatic intraepithelial neoplasia is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated serum PSA. Patients with high grade prostatic intraepithelial neoplasia should undergo repeat biopsy to exclude cancer. Further investigations are needed to optimize the treatment of patients with low grade prostatic intraepithelial neoplasia.     

Significance of Serum Free Prostate Specific Antigen in the Screening of Prostate Cancer

Purpose

The significance of serum free prostate specific antigen (PSA) in the screening of prostate cancer was examined.

Materials and Methods

A prospective clinical trial was conducted on 701 male volunteers 50 years old or older. Serum free PSA was determined and biopsies were performed if PSA was greater than 4 ng./ml. or if digital rectal examination was suspicious for cancer.

Results

Of the men 187 (27 percent) had a PSA of greater than 4 ng./ml. (11 percent) and/or a suspicious digital rectal examination (19 percent). Of 116 biopsies performed in the 701 men cancer was detected in 13 (1.9 percent). PSA detected more tumors (12 of 13, 92 percent) than digital rectal examination (9, 69 percent). Receiver operating characteristic analysis showed that the optimal free PSA-to-PSA ratio (free PSA ratio) was 12 percent. The positive predictive value for cancer according to PSA with free PSA ratio (50 percent, 10 cancers in 20 biopsies) was significantly greater (p = 0.0473) than that according to PSA alone (24 percent, 12 cancers in 50 biopsies), which indicated that 30 of 50 biopsies were avoided with only 2 cancers missed when PSA and free PSA were used for biopsy indication.

Conclusions

Free PSA determination might eliminate unnecessary biopsies in men with a PSA of more than 4 ng./ml. with minimal missed cancers.     

Parameter zur Verbesserung der Spezifit?t des prostataspezifischen Antigens

Purpose

The aim of the study was to improve the case detection rate of prostate cancer for patients who had unremarkable palpation findings and a PSA value in the range of 4 to 10?ng/ml by combination of the parameters total PSA (tPSA), f/tPSA ratio, prostate volume, PSA density, patient??s age and transrectal ultrasound findings.

Methods

Sextant biopsy of the prostate was performed for 619 patients aged 45?C75?years who had unremarkable palpation findings and PSA values in the range of 4 to 10?ng/ml. The f/tPSA ratio was determined, transrectal ultrasound examination was performed, the prostate volume was measured and the PSA density calculated. The relationship between the various test variables ?C and their combination ?C and the histology results was investigated using logistic regression.

Results

Prostate cancer was detected in 131 of 619 patients. Analysis of the aforementioned test variables by means of logistic regression revealed that the combination of the parameters f/tPSA ratio, PSA density and patient??s age can significantly increase the sensitivity and specificity of PSA in predicting prostate cancer compared with the use of these parameters on an individual basis. With an assumed limit value of 5% for performance of punch biopsy, 31% of biopsies could be avoided in practice. In such a case, only 3% of instances of prostate cancer would have gone undetected.

Conclusion

The combined use of f/tPSA ratio, PSA density and patient??s age can significantly enhance the case detection sensitivity for the PSA range of 4 to 10?ng/ml.     

Radiotherapy for High Grade Clinically Localized Adenocarcinoma of the Prostate

Purpose

We defined the efficacy of radiotherapy for the treatment of high grade (Gleason scores 8 to 10) adenocarcinoma of the prostate.

Materials and Methods

A total of 50 patients underwent radiotherapy with curative intent for clinically localized prostate cancer with Gleason scores of 8 to 10 at 1 of 4 facilities affiliated with the University of California San Francisco. Patients were considered to have biochemical failure if they had a significant increase in prostate specific antigen (PSA) of 0.5 ng./ml. per year, an increase in PSA to greater than 1.0 ng./ml. or a positive biopsy.

Results

Among the 50 patients median PSA was 22.7 ng./ml. (range 1.3 to 93.4). Tumors were clinical stage T1 or T2 in 46 percent of the cases and stage T3 or T4 in 54 percent. The overall actuarial probability of freedom from biochemical failure at 4 years was 23 percent. In a multivariate analysis including all patients pretreatment PSA was the only predictor of PSA failure, with 64 percent free of progression if the pretreatment PSA was 10 ng./ml. or less compared to only 16 percent at 3 years if PSA was more than 10 ng./ml. (p = 0.01). In a multivariate analysis restricted to patients with PSA less than 20 ng./ml. 83 percent of those treated to more than 71 Gy. were free of progression compared to 0 percent for those treated to less than 71 Gy. (p = 0.03). In a multivariate analysis PSA 10 ng./ml. or less (related risk 11.4, p = 0.02), T stage 1 or 2 (relative risk 3.8, p = 0.05) and radiation dose more than 71 Gy. (relative risk 4.0, p = 0.06) were associated with a favorable outcome.

Conclusions

At 4 years the freedom from PSA failure following radiotherapy for high grade prostate cancer was comparable to previously reported surgical series. The high failure rate among patients with PSA greater than 20 ng./ml. suggests that these patients should be considered for investigational approaches. The apparent improvement in freedom from progression with the use of higher doses provides reason for optimism.     

PROSTATE SPECIFIC ANTIGEN ADJUSTED FOR THE TRANSITION ZONE VOLUME AS AN INDICATOR OF PROSTATE CANCER

Purpose

We compared prostate specific antigen (PSA) adjusted for the transition zone volume with PSA and PSA density with regard to value in diagnosing prostate cancer in men with intermediate PSA levels of 4.1 to 10.0 ng./ml. in a community based urology practice.

Materials and Methods

Between October 1994 and May 1996, PSA transition zone was obtained from 92 of 94 men who underwent systematic sextant biopsies and had a PSA value between 4.1 and 10.0 ng./ml. PSA transition zone, calculated by dividing the PSA value by the volume of the transition zone of the prostate, was compared with PSA and PSA density via the receiver operating characteristic (ROC) curves.

Results

Of the 92 men 12 (13.0%) had prostate cancer. ROC curve analysis demonstrated that PSA transition zone and PSA density predicted the biopsy outcome significantly better than PSA (p <0.05 and p <0.01, respectively). In a subset of 59 men with normal digital rectal examination PSA transition zone predicted the biopsy outcome better than PSA density, although without significant difference. With a cutoff value of 0.3 PSA transition zone had a sensitivity of 75% and a specificity of 54%.

Conclusions

PSA transition zone is more specific than PSA in distinguishing benign from malignant disease in men with intermediate PSA levels of 4.1 to 10.0 ng./ml., especially in those with normal digital rectal examination. Further study is necessary to discuss whether PSA transition zone is superior to PSA density.     

经直肠超声引导下“10+X”点法前列腺穿刺活检术在PSA值介于4～20ng/ml之间患者前列腺癌诊断中的价值

目的 探讨经直肠超声引导下“10 +X”前列腺穿刺活检术在PSA值介于4 ～20ng/ml之间患者前列腺癌诊断中的价值。方法 回顾性分析226例血清PSA值介于4～20ng/ml之间疑似前列腺癌患者临床资料,所有患者均行经直肠超声引导下前列腺穿刺术活检。结果 前列腺癌47例,前列腺增生158例,前列腺炎11例,前列腺上...