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.     

Prostate specific antigen levels after definitive irradiation for carcinoma of the prostate.

Prostate specific antigen (PSA) levels were determined in 78 patients judged clinically to be free of disease at intervals of 36 or more months (range 38 to 186 months, median 87 months) after completion of irradiation therapy by 125iodine implantation or external beam radiation. Of this select group of patients 38% had undetectable serum PSA levels (0.5 ng./ml. or less) and 38% had PSA levels that were within normal limits (4.0 ng./ml. or less). All stages and grades were represented. Undetectable PSA levels were only rarely found (3%) in patients with carcinoma of the prostate before treatment. In 24 of these 78 patients a negative biopsy of the irradiated prostate had been obtained 18 to 42 months after treatment. When the PSA level was drawn, which ranged from 7 to 16 years after treatment, an equal percentage of these biopsied patients had either an undetectable, normal or elevated level. Irradiation is able to decrease PSA to undetectable levels in some patients with prostatic carcinoma. Whether this reflects suppression of marker production alone or, more importantly, ablation of prostate cancer producing that marker remains to be determined.     

Preoperative serum prostate specific antigen levels between 2 and 22 ng./ml. correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng./ml.

PURPOSE: Serum prostate specific antigen (PSA) is widely used as a guide to initiate prostatic biopsies and to follow men older than 50 years old with and without prostate cancer. However, benign prostatic hyperplasia (BPH) is a common cause of serum PSA values between 2 and 10 ng./ml. A better understanding of the relationships among serum PSA, prostate cancer and BPH is important. MATERIALS AND METHODS: A total of 875 men underwent radical prostatectomy at our institution between December 1984 and January 1997. Of these men 784 had a serum PSA of 2 to 22 ng./ml., including 579 with the largest cancer located in the peripheral zone of the prostate. Of the 579 men 406 had serum PSA followups for greater than 3 years after radical prostatectomy. We examined Pearson correlations (R2) between preoperative serum PSA, and the volume of Gleason grades 4/5 and 3 to 1 cancer in 784 men, separating peripheral zone from transition zone cancers. We used broken line regression with break points of 7 and 9 ng./ml. preoperative PSA to summarize the relationship of each PSA doubling to 5 different morphological variables in 579 men with peripheral zone cancer. A 9 ng./ml. break point was used for prostate weight. Trend summaries with a local regression line for the relationships between 6 morphological variables and PSA were superimposed on full scatterplots of the 579 men with PSA less than 22 ng./ml. Cox proportional hazard models were used to examine 5-year PSA failure-free probabilities based on 406 men with minimal PSA followups greater than 3 years at break points of 7 to 9 ng./ml. PSA. RESULTS: Pearson correlation between cancer volume and preoperative serum PSA in 875 men was weak (r2 = 0.27) and driven by large cancers with serum PSA greater than 22 ng./ml. For peripheral zone cancer the overall R2 x 100 for 641 men with low and high grade cancer was 10% and only 3% for low grade cancer, that is almost no PSA produced by these peripheral zone cancers enters the serum. All morphological variables changed at rates of doubtful medical significance below a PSA of 7 to 9 ng./ml. but at rates that were significantly worse above 9 ng./ml. R2 for these relationships was never greater than 15%. Large individual morphological variations at all levels of PSA emphasize the serious limitation of PSA as a predictor of prostate cancer morphology. Below 9 ng./ml. prostate weight increased by 21% for each doubling of PSA but above 9 ng./ml. the increase was only 4.8%. CONCLUSIONS: Preoperative serum PSA has a clinically useless relationship with cancer volume and grade in radical prostatectomy specimens, and a limited relationship with PSA cure rates at preoperative serum PSA levels of 2 to 9 ng./ml. Trend summaries for prostate weight on broken line regression showed that below 9 ng./ml. BPH is a strong contender for the cause of PSA elevation, constituting the primary cause of the over diagnosis of 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.     

Systematic prostatic biopsies in 100 men with no suspicion of cancer on digital rectal examination.

A total of 100 men with a mean age of 63 years underwent, in the following order, prostate specific antigen (PSA) assay (radioimmunometric assay, normal less than 2.5 ng./ml.), rectal examination, transrectal ultrasonography with a 7 MHz. probe, measurement of the prostatic volume, and 6 ultrasound-guided randomized biopsies and biopsies of any hypoechogenic zones. All men with a suspicious prostate on rectal examination (nodule, induration or firm zone) were excluded from the study. There were 14 prostatic cancers detected: 3 (8.5%) in men less than 60 years old, 4 (11%) in men between 60 and 70 years old and 7 (24%) in men more than 70 years old. No cancer was detected in men with a PSA level of less than 10 ng./ml., 5 (26%) were detected in 19 men with a PSA level of 10 to 19 ng./ml., 4 (40%) were detected in 10 men with a PSA of 20 to 29.9 ng./ml. and 5 (100%) were detected in 5 men with a PSA of 30 or more ng./ml. A total of 66 men (66%) had a PSA level of less than 10 ng./ml. There were 18 (18%) hypoechogenic zones detected: 2 (11%) were positive for cancer but, over-all, the hypoechogenic zones revealed cancer in only 2 of 100 cases (2%). In 12 of the 14 cancers detected (86%) with no clinical suspicion the PSA level was higher than the maximal PSA level related to the prostate weight. We conclude that systematic randomized prostatic biopsies are the best method of early diagnosis, detecting 41% of all prostatic cancers in men with a normal rectal examination when the PSA level is 10 ng./ml. or more. The real question is to determine whether this early diagnosis is useful for the patient, since presently, there is no certainty of the therapeutic benefit in terms of quantity and quality of life.     

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.     

The effect of digital rectal examination on the serum prostate specific antigen concentration: results of a randomized study.

To determine the effect of digital rectal examination on the serum prostate specific antigen (PSA) concentration a prospective, randomized, controlled trial involving 143 patients was conducted. Of the patients 86 (60%) had benign prostatic hyperplasia (BPH), 47 (33%) had prostate cancer and 10 (7%) had chronic prostatitis. The study group consisted of 71 men, all of whom had a serum PSA determination followed by a digital rectal examination and then a second serum PSA determination. The control cohort consisted of 72 men, all of whom had 2 serum PSA determinations without an intervening digital rectal examination. The median change in the serum PSA level for the study group was 0.4 ng./ml. compared to -0.1 ng./ml. for the control cohort (p less than 0.0001). For 76% of the study patients the second serum PSA level was greater than the initial value; only 32% of the control patients exhibited a higher second serum PSA level than the initial level (p less than 0.0001). However, only 4 patients with an initial PSA value in the reference range (0.0 to 4.0 ng./ml.) had a post-digital rectal examination value greater than 4.0 ng./ml. and only 1 patient whose presenting serum value was less than 10.0 ng./ml. had a serum PSA level greater than this cutoff point after digital rectal examination. This minimal change in serum PSA after digital rectal examination was independent of the diagnosis (BPH, cancer or chronic prostatitis), initial serum PSA concentration and examiner. Thus, although digital rectal examination had a statistically significant effect on the serum PSA concentration, the clinical significance of a 0.4 ng./ml. median increase appears inconsequential. Based on these findings, physicians should be confident that the serum PSA concentration in the immediate post-digital rectal examination period is accurate and does not compromise clinical use of the tumor marker.     

Are prostate biopsies mandatory in patients with prostate‐specific antigen increase during intravesical immuno‐ or chemotherapy for superficial bladder cancer?

BACKGROUND: Aim of this study was to evaluate if there was a significant association between intravesical immuno- or chemotherapy and the increase of PSA serum level. It could be important to avoid useless prostate biopsies. METHODS: PSA values were determined in 106 male patients who had undergone intravesical immuno- (77 cases) or chemotherapy (29 cases) from 2001 to 2005. Blood samples were obtained before and after the induction course of instillation therapy and at 3, 6, and 12 months during the maintenance course. RESULTS: 41.6% of patients at the end of the BCG induction course and 45.5% at 3 months from the beginning of the immunotherapy showed a clinically and statistically significant increase of PSA that returned to the baseline levels within 12 months. Prostate biopsies, performed in 10 patients during BCG therapy, showed inflammatory pictures in 9 cases and a prostate cancer in 1 patient with persistently elevated PSA at 12 months. In 1 case a prostate cancer was histologically found following radical cystectomy for disease progression. A statistically but not clinically significant difference of PSA level was registered in patients treated with chemotherapy. CONCLUSIONS: Our results confirm that a statistically and clinically significant PSA increase is registered during immunotherapy but not during chemotherapy. PSA elevation in patients treated with intravesical BCG is self-limited and prostate biopsies are not mandatory in these patients and could be delayed at 12 months, while monitoring PSA. On the other side, prostate biopsies are mandatory in patients with PSA abnormal elevation during chemotherapy.     

Systematic prostate biopsy before transurethral resection of the prostate

PURPOSE: With the aim of evaluating the clinical significance of systematic prostate biopsy before transurethral resection of the prostate (TUR-P), clinical data were reviewed retrospectively in patients who had underwent prostate biopsy prior to scheduled TUR-P. PATIENTS AND METHODS: Between July, 1994 and June, 2000, TUR-P was scheduled in a total number of 456 patients with clinically diagnosed benign prostatic hyperplasia (BPH). RESULTS: In 218 (47.8%) out of 456 cases, prostatic biopsy was conducted prior to TUR-P due to abnormally elevated serum prostate specific antigen (PSA) levels of 4.0 ng/ml or more, revealing only 22 (10.1%) cases of prostatic cancer. Between these 22 cases with biopsy proven prostatic cancer and 189 cases with BPH confirmed both by biopsy and following TUR-P, statistically significant differences were noted in age (p < 0.05), prostate volume (p < 0.0001) and PSA density (p < 0.01). CONCLUSION: Considering the low positive rate of preoperative prostatic biopsy, it might be suggested that a considerable number of biopsy could be avoided in patients with clinically diagnosed BPH. Based on the results obtained from this study, prostatic biopsy might be unnecessary before TUR-P for those with prostate volume greater than 60 ml or PSA density less than 0.15.     

The efficacy of cryosurgical ablation of prostate cancer: the University of California, San Francisco experience.

PURPOSE: We analyze biopsy and prostate specific antigen (PSA) results following cryosurgery for patients with clinically localized prostate cancer. MATERIALS AND METHODS: A total of 176 patients underwent 207 cryosurgical procedures for clinically localized (stages T1 to T4) prostate cancer using a multiprobe cryosurgical device. Cancer stage was T1 in 8.7%, T2 in 30%, T3 in 59% and T4 in 2.3% of the 176 patients. Neoadjuvant androgen deprivation was delivered to 101 patients (57%). End points used to determine efficacy of the procedure included analysis of posttreatment serum PSA characteristics (nadir and nonrising status) and biopsy results (absence of cancer). Cryosurgery was considered successful if PSA reached a nadir of less than 0.5 ng./ml. and did not increase by more than 0.2 ng./ml. on 2 consecutive occasions. Mean followup for the entire group was 30.8 months, with 122 patients (60%) followed for 24 or more months and 75 (36%) followed for 36 or more months. RESULTS: Serial PSA data was available after 181 initial and repeat procedures. Nadir PSA was undetectable in 88 patients (49%), between 0.1 and 0.4 ng./ml. in 39 (21%) and 0.5 ng./ml. or greater in 54 (30%) following cryosurgery. After 78 of these procedures (43%) serum PSA reached a nadir of less than 0.5 ng./ml. and failed to increase greater than 0.2 ng./ml. on at least 2 occasions. Prostate biopsy was performed following 167 procedures and was positive after 64 (38%). CONCLUSIONS: Cryosurgery was associated with favorable serum PSA characteristics in 49% of patients 3 years after treatment. Undetectable PSA nadir and pretreatment PSA 10 ng./ml. or less were associated with a favorable outcome, with a biochemical disease-free survival of 77% and 61% 3 years after treatment, respectively.     

Free-to-Total Prostate Specific Antigen Ratio as a Single Test for Detection of Significant Stage T1c Prostate Cancer

Purpose

We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels.

Materials and Methods

The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77 percent underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens.

Results

Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-total PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84 percent of stage T1c cancers were significant and comparable to stage T2 or greater cancers.

Conclusions

Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.     

Robustness of free prostate specific antigen measurements to reduce unnecessary biopsies in the 2.6 to 4.0 ng./ml. range

PURPOSE: Prostate specific antigen (PSA) cutoffs lower than 4.0 ng./ml. are being evaluated more frequently but lower PSA cutoffs increase the number of prostatic biopsies. PSA exists in several forms free and complexed to proteins. Percent free PSA is lower in men with prostate cancer. Accordingly, free PSA and complexed PSA have been used to distinguish between cancer and benign disease in the diagnostic gray zone of 4 to 10 ng./ml. to eliminate unnecessary biopsies. There are limited data on the robustness of free PSA measurements in the 2.6 to 4.0 ng./ml. total PSA range. MATERIALS AND METHODS: We evaluated percent free PSA measurements to discriminate between cancer and benign conditions in 965 consecutive volunteers in a prostate cancer screening study who underwent prostatic biopsy for a PSA of 2.6 to 4.0 ng./ml. and had benign digital rectal examination. RESULTS: Overall 25% of men had cancer detected. A 25% free PSA cutoff detected 85% of cancers and avoided 19% of negative (cancer-free) biopsies, while a 30% free PSA cutoff detected 93% of cancers and avoided only 9% of negative biopsies. Of those men who underwent radical prostatectomy 132 (80%) had pathologically organ confined tumors. Only 5% of these tumors fulfilled the published pathological criteria for possibly clinically unimportant tumors. CONCLUSIONS: Percent free PSA provides risk assessment but does not eliminate many unnecessary prostatic biopsies while maintaining a high sensitivity in the narrow total PSA range of 2.6 to 4.0 ng./ml.     

Prospective detection of clinically relevant prostate cancer in the prostate specific antigen range 1 to 3 ng./ml. combined with free-to-total ratio 20% or less: the Aarau experience

PURPOSE: Little is known about the incidence rate and clinical relevance of prostate cancer in a low prostate specific antigen (PSA) level. In a prospective PSA based screening study we investigated the incidence and clinicopathological features of prostate cancer that occurred within PSA range 1 to 3 ng./ml. when the free-to-total ratio was 0.20 or less. MATERIALS AND METHODS: Men participating in the Aarau, Switzerland, section of the European Randomized Study of Screening for Prostate Cancer between October 1998 and July 2000 were included in the study. As a side study, all men with PSA between 1 and 3 ng./ml. and free-to-total ratio 0.20 or less were invited to undergo further evaluation with ultrasound guided sextant prostate biopsy. RESULTS: Overall, 168 (7.8%) participants fulfilled inclusion criteria. A total of 158 (94%) patients underwent prostate biopsy, and prostate cancer was detected in 17 (10.8%). There were no statistically significant differences between prostate cancer and benign prostatic hyperplasia in regard to patient age (60.7 versus 59.8 years), prostate volume (23.9 versus 23.0 cc), PSA (1.98 versus 1.86 ng./ml.), free-to-total ratio (0.161 versus 0.160), PSA density (0.089 versus 0.076 ng./ml.) or PSA transition zone density (0.33 versus 0.24 ng./ml., respectively). Median Gleason score was 5 on prostate biopsy versus 6 on retropubic prostatectomy specimen. Of the 14 patients who underwent surgery there were positive lymph nodes in 1, stage pT3b Gleason 7 disease in 1, and pathologically organ confined Gleason 5 in 2, Gleason 6 in 5 and Gleason 7 in 5. Mean tumor volume was 1.01 cc (range 0.02 to 5.17). There were 2 (14.3%) insignificant (less than 0.2 cc, Gleason grade 3 or less), 1 (7.1%) minimal (less than 0.5cc, Gleason grade 3 or less) and 11 (78.6%) clinically relevant and potentially harmful cancers. CONCLUSIONS: There is a significant number of prostate cancer cases diagnosed at PSA as low as 1 to 3 ng./ml. A majority of these tumors are clinically significant. This free-to-total ratio range may be helpful for identifying prostate cancer. The "window of opportunity" for detection of curable cancer may change in populations with higher life expectancy towards lower PSA. Lack of specificity and characterization of tumor aggressiveness remains an unsolved issue for PSA.     

Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer: prostate specific antigen is superior to all other clinical parameters.

Presently, the standard staging evaluation of prostate cancer includes digital rectal examination, measurement of serum tumor markers and a radionuclide bone scan. To evaluate the ability of local clinical stage, tumor grade, serum acid phosphatase, serum prostatic acid phosphatase (PAP) and serum prostate specific antigen (PSA) to predict bone scan findings, a retrospective review of 521 randomly chosen patients (mean age 70 years, range 44 to 92 years) with newly diagnosed, untreated prostate cancer was performed. Local clinical stage, tumor grade, acid phosphatase, PAP and PSA all correlated positively with bone scan findings (p less than 0.0001). Using receiver operating characteristic curves, however, PSA had the best over-all correlation with bone scan results. The median serum PSA concentration in patients with a positive bone scan was 158.0 ng./ml., whereas men with a negative bone scan had a median serum PSA level of 11.3 ng./ml. (p less than 0.0001). Using multivariate logistic regression analysis, local clinical stage, tumor grade, acid phosphatase and PAP were evaluated in combination with PSA to assess whether these parameters increased the ability of PSA alone to predict bone scan findings. None of these clinical parameters, irrespective of the combination used, contributed appreciably to the predictive power of PSA alone. A probability plot with 95% confidence intervals was constructed that allows the practicing urologist to estimate on an individual basis the probability of a positive bone scan for any given serum PSA value. The most significant finding of this study, however, was the negative predictive value of a low serum PSA concentration for bone scan findings. In 306 men with a serum PSA level of 20 ng./ml. or less only 1 (PSA 18.2 ng./ml.) had a positive bone scan (negative predictive value 99.7%). This finding would suggest that a staging radionuclide bone scan in a previously untreated prostate cancer patient with a low serum PSA concentration may not be necessary.     

Prostate specific antigen nadir following external beam radiation therapy for clinically localized prostate Cancer: The relationship between nadir level and disease-free survival

Purpose

We determined whether the prostate specific antigen (PSA) nadir achieved following external beam radiation therapy alone predicts biochemical disease-free survival in a large cohort of men with clinically localized prostate cancer.

Materials and Methods

Between January 1986 and October 1993, 364 men with clinically localized, stages T1 to T3 adenocarcinoma of the prostate received definitive external beam radiation therapy with no prior, concomitant or adjuvant endocrine therapy. PSA was measured before treatment in 326 men (90 percent) and serial PSA was measured following treatment in all patients. All men were followed continuously for at least 24 months (median 44 months, range 24 to 90, mean 46). Biochemical failure after irradiation was defined as PSA of 1.5 ng./ml. or more and 2 consecutive serum PSA elevations.

Results

The 5-year overall biochemical disease-free survival rate for the entire group was 56 percent. PSA nadir was predictive of subsequent biochemical disease-free survival. The biochemical disease-free survival rate at 3 years was 93, 49 and 16 percent for PSA nadirs of 0 to 0.99, 1 to 1.99 and 2 or more ng./ml., respectively (p = 0.0001). In a multivariate analysis PSA nadir (0 to 0.99 versus 1.0 to 1.99 versus 2 or more ng./ml.) was an independent predictor of biochemical disease-free survival along with pretreatment PSA, central axis dose, Gleason grade and T stage.

Conclusions

PSA nadir after radiation therapy is an indicator of subsequent biochemical disease-free survival. Patients who achieve a nadir of less than 1 ng./ml. following external beam radiation therapy have a favorable biochemical disease-free survival rate, while those with a nadir of greater than 1 ng./ml. have a high subsequent failure rate. Strategies to improve results should focus on techniques to increase the likelihood of achieving a PSA nadir of less than 1 ng./ml.     

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.     

膀胱移行细胞癌伴前列腺癌的诊断与治疗

目的　提高膀胱移行细胞癌伴前列腺癌的诊治水平。　方法　对 8例膀胱移行细胞癌伴前列腺癌患者的临床资料进行分析。　结果　 8例术前均经膀胱镜检查及活检病理证实为膀胱移行细胞癌。 7例经直肠前列腺穿刺活检确诊前列腺癌 ,1例为前列腺增生症 ,行膀胱前列腺全切术后病理证实为前列腺癌。 4例行经尿道膀胱肿瘤电切及双侧睾丸切除术 ,术后使用丝裂霉素或BCG等膀胱灌注及氟他胺内分泌治疗。 1例行膀胱前列腺全切加回肠膀胱术。 8例中 2例失访 ,3例因多发性转移 ,术后存活 <1年 ,3例行根治性膀胱前列腺全切术 ,术后随访 1.5～ 4.0年 ,经胸片、CT、同位素和PSA等检查未见肿瘤复发或转移。　结论　血清PSA测定、前列腺直肠指诊、经直肠前列腺B超检查、活检及膀胱镜检查是诊断膀胱移行细胞癌伴前列腺腺癌的主要方法 ,根治性膀胱前列腺切除是影响预后的重要因素     

Discrimination of benign from malignant prostatic disease by selective measurements of single chain,intact free prostate specific antigen

PURPOSE: Free prostate specific antigen (PSA) in serum consists of heterogeneous molecular subforms. Recently we developed an immunoassay for selective measurement of a subfraction of free PSA called intact PSA, which has been shown to be closely associated with prostate cancer. We assessed the ability of serum intact PSA to discriminate between benign and malignant prostatic disease. MATERIALS AND METHODS: In serum of 178 men with benign disease and 255 men with prostate cancer we measured total PSA and free PSA using a commercially available immunoassay. Intact PSA levels were analyzed by a newly developed assay specific for noncleaved, that is single chain forms of free PSA. Internally cleaved "nicked" PSA was calculated by subtracting intact from free PSA. We also calculated ratios of intact PSA-to-free PSA (intact-to-free PSA) and nicked PSA-to-total PSA (nicked-to-total PSA). We compared means, medians and ranges of all analytes and ratios in patients with and without cancer for the entire total PSA range and in a subset with total PSA ranging from 2 to 10 ng./ml. Furthermore, various combinations of PSA forms were tested for their predictive ability. For statistical comparison we used the Mann-Whitney U test and ROC analysis. RESULTS: The ratio intact-to-free PSA was significantly higher in cancer (median 48.5%) compared to noncancer cases (median 41.8%, p <0.0001). Conversely, the ratio nicked-to-total PSA was significantly higher in men without compared to those with prostate cancer (median 11.0% and 6.0%, respectively, p <0.0001). Highest discriminative ability was observed for a combination of intact, total and free PSA (log [intact, free, total], AUC = 0.773) followed by nicked-to-total PSA (AUC 0.755). In the subgroup of patients with total PSA levels from 2 to 10 ng./ml. only the AUC of log intact, free, total (AUC 0.706, p = 0.0017) and nicked-to-total PSA (AUC 0.704,p = 0.0019) were significantly larger compared to the AUC of total PSA (AUC 0.602). CONCLUSIONS: By contrast to measuring crude free PSA concentration, selective determination of specific free PSA subforms, intact PSA and nicked PSA proved to be useful to discriminate men with benign from malignant prostatic disease. These markers may serve to generate specific serum profiles of PSA for improved specificity and early detection of prostate cancer. To translate the encouraging statistical advantage shown in this study into a clinically applicable tool warrants further investigation.     

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.     

SERUM AND SEMEN PROSTATE SPECIFIC ANTIGEN CONCENTRATIONS ARE DIFFERENT IN YOUNG SPINAL CORD INJURED MEN COMPARED TO NORMAL CONTROLS

PURPOSE: Recent investigations have indicated that factors within the seminal plasma may contribute to the condition of low sperm motility in men with spinal cord injury. To determine whether the prostate gland functions normally in these men we chose prostate specific antigen (PSA) as a marker of prostatic function, and compared serum and semen concentrations in spinal cord injured and healthy noninjured men. MATERIALS AND METHODS: The study included 21 spinal cord injured men (mean age 33.3+/-1.2 years) and 22 noninjured normal men (mean age 30.3+/-1.5 years). Blood was obtained from subjects following at least 24 hours of abstinence from ejaculation and serum PSA was determined by modified enzyme immunoassay. Antegrade ejaculates from all subjects were frozen to -80 C, exactly 15 minutes after collection. Seminal plasma PSA was determined using Hybritech Tandem MP assay. RESULTS: Mean serum PSA concentration was 1.20+/-0.19 ng./ml. in spinal cord injured and 0.69+/-0.07 ng./ml. in noninjured men (p<0.02). Mean seminal plasma PSA concentration was 0.59+/-0.11 mg./ml. in spinal cord injured and 1.29+/-0.15 mg./ml. in noninjured men (p<0.001). CONCLUSIONS: Our findings of elevated serum and decreased seminal plasma PSA concentrations indicate that prostatic secretory dysfunction is present in men with spinal cord injury.