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.     

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.     

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.     

Prognostic significance of the nadir prostate specific antigen level after hormone therapy for prostate cancer

PURPOSE: We determine whether the nadir prostate specific antigen (PSA) level after hormone therapy can be used to predict the progression to hormone refractory prostate cancer. MATERIALS AND METHODS: We reviewed the progressive status and survival of 177 patients with stage C or D prostate cancer who had received hormone therapy at our institution. The overall survival rate, incidence of progression to hormone refractory prostate cancer and interval until progression were analyzed with reference to the nadir PSA level. Multiple regression analysis was used to analyze the predictive factors for progression to hormone refractory prostate cancer, and the relative efficacy of the nadir PSA level in predicting progression was evaluated by receiver operating characteristics analysis. RESULTS: Median followup was 39 months (range 3 to 89) and 85.4% of patients (151) responded to treatment, of whom 77.5% (117) had progression to hormone refractory prostate cancer. Median time until nadir PSA levels were reached after hormone therapy was 8.1 months and median time until hormone refractory prostate cancer was 24.0 months. Nadir PSA levels were less than 0.2 ng./ml. in 31% of respondents, 0.2 to 1.0 ng./ml. in 23%, 1.1 to 10 ng./ml. in 42% and greater than 10 ng./ml. in 5%. These groups had similar clinicopathological characteristics. Nadir PSA levels correlated significantly with pretreatment PSA levels, Gleason scores and progression to hormone refractory prostate cancer (p = 0.01, p <0.01 and p <0.001, respectively), and inversely correlated with the interval to the establishment of hormone refractory prostate cancer (r = -0.465, p <0.05). By univariate analysis bone metastasis, nadir PSA, PSA at 6 months after treatment and pretreatment PSA were significantly associated with progression to hormone refractory prostate cancer. Only the nadir PSA was calculated to be an independent factor by multivariate analysis. Receiver operating characteristics analysis indicated that nadir PSA predicted progression to hormone refractory prostate cancer after 2 years with an accuracy of 86.2%. With the lower limit of the nadir PSA level set to 1.1 ng./ml., sensitivity was 80.3% and specificity was 83.8%, and these levels were deemed the most appropriate. Furthermore, nadir PSA after hormone therapy was an independent prognosticator for survival, as were initial levels of hemoglobin and alkaline phosphatase. CONCLUSIONS: The nadir PSA level after hormone therapy may be the most accurate factor predicting the progression to hormone refractory prostate cancer and is an independent prognostic factor for survival. Furthermore, a lower limit for the nadir PSA level of 1.1 ng./ml. gives optimal sensitivity and specificity.     

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.     

A comparison of the free fraction of serum prostate specific antigen in men with benign and cancerous prostates: the best case scenario

Purpose

In most previous studies of free-to-total serum prostate specific antigen (PSA) ratios, the specimens from patients with prostate cancer or those with benign prostatic hyperplasia (BPH) have not been highly characterized. We compared preoperative sera from post-radical prostatectomy patients with clinically significant cancers of at least 2 cm.³ to sera from those with BPH and large, biopsy negative prostates.

Materials and Methods

We used 2 different time resolved immunofluorometric assays for free and total PSA, and a combination of a chemoluminescent immunoassay for free PSA detection with an immunoradiometric assay for total PSA to measure free and total PSA. The serum ratios of free-to-total PSA in these assays were compared to those obtained previously from gel filtration studies. Sera from 51 men with prostate cancer volumes of 2 to 18 cm.³ were compared to those from 48 men with BPH and a mean prostate volume of 78 plus/minus 7 cm.³. The respective mean serum PSA levels plus or minus standard deviation were 10.0 plus/minus 6.3 and 8.9 plus/minus 7.2 ng./ml.

Results

Monoclonal assays for free PSA confirmed the previous study with gel filtration. For PSA 4 to 10 ng./ml., 94 to 95 percent of the men with prostate cancer were correctly diagnosed, with a cutoff of less than 15 percent for free-to-total PSA on immunofluorometric assay and less than 14 percent for chemoluminescent immunoassay with immunoradiometric assay. However, 46 percent (immunofluorometric assay) and 36 percent (chemoluminescent immunoassay and immunoradiometric assay) of men with BPH did not have enough free PSA for diagnosis of BPH (that is 36 to 46 percent false-positive rate).

Conclusions

For total PSA 4 to 10 ng./ml., the sensitivity of approximately 15 percent free-to-total PSA for prostate cancer is high (94 to 95 percent) but 36 to 46 percent of men with BPH and a large gland will not be correctly identified. For PSA 2 to 4 ng./ml., no ratio of percent free-to-total PSA discriminated BPH from prostate cancer.     

A standard definition of disease freedom is needed for prostate cancer: undetectable prostate specific antigen compared with the American Society of Therapeutic Radiology and Oncology consensus definition

PURPOSE: Freedom from prostate cancer is defined by undetectable prostate specific antigen (PSA) after surgery and the American Society of Therapeutic Radiology and Oncology (ASTRO) criteria are recommended for irradiation. Whether these definitions of disease freedom are comparable was evaluated in this study. MATERIALS AND METHODS: From August 1992 to August 1996 simultaneous irradiation with prostate 125iodine implantation followed by external beam irradiation was performed in 591 consecutive men with stage T1T2NX prostate cancer. All patients had a transperineal implant and none received neoadjuvant hormones. Disease freedom was defined by a PSA cutoff of 0.2 ng./ml. and the ASTRO consensus definition. Median followup was 6 years (range 5 to 8). RESULTS: Of the 591 men in this study 65 had recurrence by ASTRO criteria and 93 had recurrence by a PSA cutoff of 0.2 ng./ml., which was a significant difference (p = 0.001). On multivariate analysis of the factors related to disease-free status the definition of disease freedom, pretreatment PSA and Gleason score were highly significant. Of the 528 men with a minimum 5-year PSA followup the 8-year disease-free survival rate by ASTRO criteria was 99% in those who achieved a PSA nadir of 0.2 ng./ml. and 16% in those with a nadir of 0.3 to 1 ng./ml. Of the 469 disease-free patients by ASTRO criteria with a minimum 5-year followup 455 (97%) achieved a PSA nadir of 0.2 ng./ml. or less. CONCLUSIONS: The definition of freedom from prostate cancer significantly affects treatment results. A standard definition is needed and a PSA cutoff of 0.2 ng./ml. is suggested as the standard for all curative treatments for localized prostate cancer.     

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.     

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.     

Time to achieve a prostate specific antigen nadir of 0.2 ng./ml. after simultaneous irradiation for prostate cancer

PURPOSE: A prostate specific antigen (PSA) cutoff point of 0.2 ng./ml. has been suggested as the standard definition of disease freedom for curative treatment of localized prostate cancer. The time to achieve this goal after irradiation was determined in this study. MATERIALS AND METHODS: From August 1992 to December 1996, 539 consecutive men with clinical stage T1T2NX prostate cancer who had a minimum 5-year PSA followup and achieved a PSA nadir of 0.2 ng./ml. without hormones were evaluated. All patients were treated with simultaneous irradiation with a transperineal prostate iodine implant, followed by external beam irradiation. Time to achieve a PSA of 0.2 ng./ml. was retrospectively calculated from the date of implantation in all men and according to various factors. Recurrence was defined as a subsequent increase above a PSA of 0.2 ng./ml. Minimum followup was 5 years (median 6.5, range 5 to 9). RESULTS: In all 539 men the median time to a PSA nadir of 0.2 ng./ml. was 27 months, while 534 (99%) achieved this level by 60 months of followup. Median time to achieve this PSA goal was 20 and 39 months in patients without and with a PSA bounce, respectively. Pretreatment PSA, disease status and ultimately PSA bounce, Gleason score and stage had little or no effect on time to a PSA of 0.2 ng./ml. CONCLUSIONS: With rare exceptions to be potentially cured of prostate cancer by simultaneous irradiation men must achieve a PSA nadir of 0.2 ng./ml. within 5 years of implantation. Failure to reach this goal by 60 months of followup almost always indicates persistent disease.     

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.     

Standard Versus Age-Specific Prostate Specific Antigen Reference Ranges Among Men With Clinically Localized Prostate Cancer: A Pathological Analysis

Purpose

Age-specific prostate specific antigen (PSA) reference ranges have been suggested to account for the age-dependent nature of the serum PSA concentration. It has been hypothesized that reference ranges of 0 to 2.5 ng./ml. serum PSA (40 to 49 years), 0 to 3.5 ng./ml. (50 to 59 years), 0 to 4.5 ng./ml. (60 to 69 years) and 0 to 6.5 ng./ml. (70 to 79 years) would detect fewer (potentially insignificant) prostate cancers in older men and more (potentially curable) cancers in younger men.

Materials and Methods

To investigate the pathological stage of tumors that would be affected by the use of age-specific PSA reference ranges, we reviewed the medical records for 4,597 men with clinically localized (stage T1c, T2 or T3a) prostate cancer, with an average age of 62 plus/minus 7 years (range 38 to 76), who underwent radical prostatectomy between 1984 and 1994 at our institutions. Favorable pathological results were defined as organ-confined disease or capsular perforation with a Gleason score of less than 7, and unfavorable pathological results were defined as capsular perforation with a Gleason score of 7 or more, seminal vesicle invasion or lymph node involvement.

Results

Overall, 18 percent of the men had PSA levels less than the standard PSA reference range (4.0 ng./ml.) compared to 22 percent when using the age-specific ranges. There were 74 more cancers detected in men younger than 60 years with the use of age-specific ranges, of which 81 percent had favorable pathological results. Among the men 60 years or older, 191 of 252 cancers (76 percent) not detected by using age-specific ranges were of favorable pathological status. Of those cancers not detected in older men with the age-specific ranges less than 3 percent were also stage T1c and 95 percent of these undetected T1c cancers were of favorable pathological status. Age-specific PSA reference ranges increased the potential for detection of prostate cancer by 18 percent in the younger men and decreased the detection by 22 percent in the older men.

Conclusions

Among these men with clinically localized prostate cancer, age-specific PSA reference ranges increased the detection of more potentially curable tumors in young men and decreased the detection of less advanced tumors in the older men compared to the standard reference range of 4.0 ng./ml. Among older men with nonpalpable (stage T1c) tumors age-specific PSA reference ranges would have detected fewer tumors. However, 95 percent of these “missed” tumors would have had favorable pathological findings.     

Clinical Efficacy of Bone Alkaline Phosphatase and Prostate Specific Antigen in the Diagnosis of Bone Metastasis in Prostate Cancer

Purpose

We investigated the usefulness of bone alkaline phosphatase isoenzyme and prostate specific antigen (PSA) determined by radioimmunoassay to predict bone scan evidence of metastasis in newly diagnosed untreated and treated prostate cancer.

Materials and Methods

We analyzed bone alkaline phosphatase enzyme concentrations in 350 men, including 150 controls, 100 with benign prostatic hyperplasia and 100 with prostate cancer (52 with stage T1 to 4, M0 and 48 with stages T1 to 4, M1 to 4). We also analyzed bone alkaline phosphatase enzyme concentrations in 61 stages T1 to 4, M0 prostate cancer cases during followup after radical prostatectomy or hormonal therapy, and 17 had clinical progression (9 with local, 5 with lymph node and 3 with bone metastases). Simultaneously, we analyzed PSA concentrations.

Results

Average bone alkaline phophatase enzyme levels were 12, 11.1 and 10.0 ng./ml. in the control, benign prostatic hyperplasia and stage M0 prostate cancer groups, respectively (p not significant), and 83.2 ng./ml. in patients with stage M1 to 4 disease (p less than 0.001). Considering that to diagnose bone metastasis the cutoff for bone alkaline phosphatase enzyme and PSA is 30 ng./ml. and 100 ng./ml., respectively, clinical effectiveness was 93.7 percent and 81.8 percent, respectively. Finally, measurement of both substances at the same time increased clinical effectiveness to 97.9 percent. During followup a bone alkaline phosphatase enzyme level that becomes greater than 30 ng./ml. (0 percent in the local and lymphatic progression groups, and 100 percent in the bone metastasis group) indicates the need to perform a bone scan.

Conclusions

We recommend the clinical use of bone alkaline phosphatase enzyme determined by radioimmunoassay and PSA measurement for the diagnosis of bone metastases and progression of prostate cancer because of the good sensitivity and specificity.     

INFLUENCE OF FINASTERIDE ON FREE AND TOTAL SERUM PROSTATE SPECIFIC ANTIGEN LEVELS IN MEN WITH BENIGN PROSTATIC HYPERPLASIA

Purpose

Finasteride therapy for benign prostatic hyperplasia (BPH) results in a marked lowering of serum prostate specific antigen (PSA) levels. However, little is known about the effect of finasteride on unbound or free serum levels of PSA. Such information would be important since percent free PSA may substantially improve the cancer specificity of PSA testing. Thus, we prospectively studied the effect of finasteride therapy on total and free serum PSA levels.

Materials and Methods

In a randomized, placebo controlled, double-blind trial 40 men with histologically confirmed BPH (age range 52 to 78 years) were treated with either 5 mg. finasteride daily (26 patients) for 9 months or placebo (14) for 6 months. Prostate volume was assessed by transrectal ultrasound. Serum levels of free and total PSA were measured from archived serum samples stored at −70C at baseline and for as long as 9 months of treatment.

Results

In the finasteride group mean total PSA levels declined from 3.0 ng./ml. at baseline to 1.5 ng./ml. after 6 months of treatment (50% decrease, p < 0.01). In the placebo group, with similar baseline levels, no significant change was observed. PSA density declined significantly in finasteride treated men (p <0.01) but not in men receiving placebo. The mean percent free PSA (13 to 17% at baseline) was not altered significantly by finasteride or placebo.

Conclusions

Total PSA serum levels decreased by an average of 50% during finasteride therapy but percent free PSA did not change significantly. This information is potentially useful in the interpretation of PSA data used for early detection of prostate cancer in men receiving finasteride. However, further studies are required to demonstrate the use of percent free PSA to detect the development of cancer.     

PSA nadir is a significant predictor of treatment failure after high-intensity focussed ultrasound (HIFU) treatment of localised prostate cancer

OBJECTIVES: To assess if prostate-specific antigen (PSA) nadir is an independent predictor of treatment failure and disease-free survival after high-intensity focussed ultrasound (HIFU) therapy for localised prostate cancer as defined by the new ASTRO criteria. METHODS: One hundred three patients after HIFU treatment (Ablatherm, EDAP, Lyon, France) for localised prostate cancer without previous hormonal therapy were evaluated retrospectively. Patients attended regular follow-up visits every 3 mo. Treatment failure was defined by the revised ASTRO criteria (PSA >or=2 ng/ml above nadir PSA, positive biopsy, if salvage treatment was administered). Patients were divided into three PSA nadir subgroups (group 1, 1 ng/ml). The disease-free survival rate (DFSR) was calculated by using life table methods. The log-rank test was used to compare the curves based on Kaplan-Meier models. RESULTS: The median follow-up was 4.9 (3-8.6) yr. Mean time to PSA nadir was 6.4+/-5.1 mo. A PSA nadir of 1ng/ml was reached by 64%, 22.3%, and 13.6% of patients, respectively. Treatment failure rates during follow-up were 4.5%, 30.4%, and 100%, respectively, for the three groups (p<0.001). The actuarial DFSRs at 5 yr were 95%, 55%, and 0%, respectively, for the 3 groups (p<0.001). CONCLUSIONS: The PSA nadir after HIFU correlates highly significantly with treatment failure and DFSR, and can be applied in daily clinical practice. Promising oncological outcome is obtained if a PSA nadir of 相似文献   

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.     

Sensitive Prostate Specific Antigen Measurements Identify Men With Long Disease-Free Intervals and Differentiate Aggressive from Indolent Cancer Recurrences within 2 Years After Radical Prostatectomy

Purpose

Commonly available prostate specific antigen (PSA) assays have detection limits of greater than 0.05 ng./ml., limiting their ability to identify residual or recurrent prostate cancer after radical prostatectomy or to provide prognostic information within the first several years after surgery. We investigated the ability of a sensitive PSA assay to identify residual prostate cancer and men at risk for early recurrence after radical prostatectomy.

Materials and Methods

We measured PSA in 1,037 serum samples obtained serially from 127 men after radical prostatectomy using the IMMULITE' third generation PSA assay.'Diagnostic Products Corp., Los Angeles, California.

Results

The IMMULITE PSA assay has an analytical sensitivity of less than 0.002 ng./ml. and a clinically useful decision threshold of 0.01 ng./ml. With this assay our patients were classified into 3 groups: 1) 50 with a postoperative baseline PSA of less than 0.01 ng./ml. that did not change during an average of 36 months postoperatively, 2) 66 with increasing PSA that exceeded 0.01 ng./ml. in all cases by 30 months postoperatively (20 with clinical cancer recurrences) and 3) 11 with slowly increasing PSA of greater than 0.01 but less than 0.02 ng./ml. at an average of 36 months postoperatively.

Conclusions

The IMMULITE PSA assay provides clinically useful information not previously available from PSA assays with conventional sensitivity, which is highly predictive of cancer activity in patients within 2 years after radical prostatectomy.     

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.     

Pitfalls in Interpreting Prostate Specific Antigen Velocity

Purpose

The concept of prostate specific antigen (PSA) velocity as an improved marker for prostate cancer detection is intriguing. However, before this concept is applied to individual patients several confounding parameters must be addressed. We determined the variability of serum PSA levels in men without prostate cancer.

Materials and Methods

We reviewed data from a prostate cancer screening program, and determined inter-assay and individual variability of the serum PSA values for a 2-year followup period in 265 men clinically free of prostate cancer.

Results

Our average inter-assay coefficient of variation was 7.5 percent. Therefore, we considered only PSA changes exceeding plus/minus 15 percent as significant. Fluctuations in serum PSA occurred in 78 percent of the men during the observation period, and 12.5 percent had at least a single PSA increase exceeding 0.75 ng./ml. per year. Fluctuations were noted throughout the entire range of serum PSA levels but became progressively larger with an increasing mean PSA.

Conclusions

The inter-assay variability must be considered when interpreting PSA velocity. Individual fluctuations in serum PSA dictate an observation period of at least 2 years before PSA velocity is considered abnormal.     

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.