RELATIONSHIP BETWEEN SYSTEMATIC BIOPSIES AND HISTOLOGICAL FEATURES OF 222 RADICAL PROSTATECTOMY SPECIMENS: LACK OF PREDICTION OF TUMOR SIGNIFICANCE FOR MEN WITH NONPALPABLE PROSTATE CANCER

PURPOSE: Because of the recent increase in nonpalpable prostate cancer (clinical stage T1c) in men, preoperative needle biopsy findings have had an important role for treatment decisions. We examine the correlation among histopathological features of 6 systematic biopsies and radical prostatectomy specimens in which 1 investigator reviewed all histological sections. MATERIALS AND METHODS: We studied a total of 450 men with clinical stage T1c prostate cancer from whom needle biopsies were matched with radical prostatectomy specimens, and selected 222 patient biopsies that were obtained from 6 or more separate regions of the prostate. The pretreatment parameters of serum prostate specific antigen (PSA), PSA density, number of positive needle biopsies, distribution of positive cores, linear cancer length, and percent Gleason grade 4/5 on the biopsy were determined and compared with histopathological features of prostate cancer in the radical prostatectomy specimens. All biopsies and radical prostatectomies were evaluated morphologically at the department of urology. RESULTS: Of the 222 men the largest cancer was clinically insignificant in 23 (10%), as measured by a cancer volume of less than 0.5 cc. Cancer volume in the prostatectomy specimen was significantly related to all parameters in the biopsy, with the surprising exception of cancer distribution in the positive biopsies. However, all of these correlations with cancer volume were weak, with Pearson's correlation squared (R(2)) multiplied by 100 less than 10%. Unfortunately, tumor grade on the biopsy agreed with the prostatectomy specimen in only 81 of 222 (36%) cases. Grade assessment with needle biopsy underestimated the tumor grade in 102 (46%) cases and overestimated it in 39 (18%). No single parameter in the biopsy was a predictor of tumor significance, as measured by a cancer volume of greater than 0.5 cc. However, the best model to predict a tumor less than 0.5 cc in volume was the combination of a single positive core with cancer length less than 3 mm. that contained no Gleason grade 4/5. The use of PSA or PSA density in combination with needle biopsy findings did not enhance prediction of tumor significance. CONCLUSIONS: These results indicate a weak and disappointing correlation among all pathological features of 6 systematic biopsies and radical prostatectomy specimens. The combination of 1 positive core with cancer length less than 3 mm. that contains no Gleason grade 4/5 is probably the best predictor of prostate cancer less than 0.5 cc in men with nonpalpable tumors, a cancer volume that occurred in only 10% of the 222 (23) men.     

LACK OF ASSOCIATION OF PROSTATE CARCINOMA NUCLEAR GRADING WITH PROSTATE SPECIFIC ANTIGEN RECURRENCE AFTER RADICAL PROSTATECTOMY

PURPOSE: Grading prostate cancer using the Gleason system relies only on architectural tumor growth, in contrast to other systems, such as the WHO system, which grade prostate carcinoma based on nuclear features as well as architectural patterns. The prognostic significance of nuclear grading remains controversial since most studies were performed before prostate specific antigen (PSA) screening became widely available. We evaluated the significance of nuclear grade for predicting PSA recurrence in a contemporary cohort of patients treated with radical prostatectomy for clinically localized prostate carcinoma. MATERIALS AND METHODS: Nuclear grades 1 to 3 were determined in 141 consecutive radical prostatectomies in 1995. Predominant and worst nuclear grade was determined by a consensus of 3 pathologists. Statistical analysis compared nuclear grade with Gleason score using the chi-square test. The Cox proportional hazards analysis was performed to calculate the ability of nuclear grade, Gleason score and other variables to predict PSA recurrence. RESULTS: We identified a significant association of Gleason score with worst nuclear grade (p = 0.007). All 6 cases with a Gleason score of 8 or greater had a worst nuclear grade of 3, in contrast to 36 of 60 (60%) with a score 6 or less, in which the worst nuclear grade was 3. Of the 141 patients 31 (21.9%) had PSA recurrence at a median followup of 3.7 years. The univariate Cox model revealed significant associations of PSA recurrence with Gleason score 8 or greater (hazards ratio 5.5, p = 0.005), extraprostatic extension (hazards ratio 3.4, p = 0.001), positive surgical margin (hazards ratio 2.6, p = 0.009), seminal vesicle involvement (hazards ratio 7.3, p <0.001), preoperative serum PSA (hazards ratio 1.03, p = 0.007), tumor stage (hazards ratio 3.6, p = 0.001) and maximal tumor dimension (hazards ratio 2.4, p <0.001). However, overall and worst nuclear grade did not predict PSA recurrence (p = 0.89 and 0.13, respectively). Nuclear grade did not fit any multivariate model tested, which otherwise included Gleason score, log(PSA), surgical margin status, extraprostatic extension, seminal vesicle status, tumor size and pathological stage. By varying sample fixation time we also showed that benign prostate tissue in the same section as prostate carcinoma had grade 2 or 3 nuclear changes, that is moderate to marked anaplasia. CONCLUSIONS: High nuclear grade is associated with high Gleason score. However, prostate carcinoma with a Gleason score of 6 or less shows extreme variability. Nuclear grade determined by light microscopy failed to predict PSA recurrence in a contemporary series of men with clinically localized prostate cancer treated with radical prostatectomy. Nuclear morphology is subject to tissue fixation and processing artifact. Any nuclear morphometric study must consider this artifact.     

HEALTH RELATED QUALITY OF LIFE ASSESSMENT AFTER RADICAL PROSTATECTOMY IN MEN WITH PROSTATE SPECIFIC ANTIGEN ONLY RECURRENCE

PURPOSE: The health related quality of life assessment is becoming increasingly important among patients with prostate cancer. Meanwhile, treatment of patients with increasing prostate specific antigen (PSA) after radical retropubic prostatectomy remains controversial. We attempt to define the impact of PSA recurrence on the health related quality of life of patients after radical retropubic prostatectomy. MATERIALS AND METHODS: Of 604 consecutive patients who underwent radical retropubic prostatectomy between March 1991 and September 1998, 510 (84%) were available for followup. Each patient was mailed the RAND 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index questionnaire. A total of 348 (70%) questionnaires were returned. Health related quality of life scores were then compared between patients with and without PSA recurrence. A multivariate analysis was also performed to elucidate further the cause of differences between the groups. RESULTS: Overall, 88 (25%) patients had PSA recurrence. In regard to health related quality of life there were small (less than 10%) but statistically significant differences in 2 of 4 physical health domains (RAND 36-Item Health Survey). There was a significant decrease in only 1 category of the mental health domain for patients with PSA recurrence. Only sexual function was statistically lower on the University of California, Los Angeles, Prostate Cancer Index. This result reflects the lower incidence of nerve sparing in these patients, as confirmed by the multivariate analysis. Overall patient satisfaction was similar between those with and without PSA recurrence (76% and 79%, respectively). CONCLUSIONS: Our study demonstrates small health related quality of life differences in patients with biochemical PSA recurrence versus those without. These findings provide a baseline assessment of general and disease specific health related quality of life domains among these patients. Future studies should focus on differences in the measure of cancer anxiety before and after administration of adjuvant therapy in these asymptomatic patients.     

DIGITAL RECTAL EXAMINATION AND IMAGING STUDIES ARE UNNECESSARY IN MEN WITH UNDETECTABLE PROSTATE SPECIFIC ANTIGEN FOLLOWING RADICAL PROSTATECTOMY

PURPOSE: We determine the probability of local or distant recurrence following radical prostatectomy in men with an undetectable prostate specific antigen (PSA) level. MATERIALS AND METHODS: The clinical course of 1,916 consecutive men followed during a 14-year period after radical prostatectomy was reviewed. Average followup plus or minus standard deviation is 5.5+/-3.5 years, and 326 men (17%) have been followed for more than 10 years. In total this population of men has been followed for 10,540 patient-years. RESULTS: Of 1,916 men 56 (2.9%) had local recurrence an average of 6.1+/-2.7 years (range 1 to 12) after surgery. No man had local recurrence with an undetectable serum PSA. Mean serum PSA at the time of local recurrence was 5.8 ng./ml. Of the 56 men 13 (25%) who had local disease recurrence had an undetectable serum PSA at 5 years of followup but had progression to biochemical and local disease recurrence later. Of 1,916 men 118 had distant metastases with a mean serum PSA of 28.6 ng./ml. No man has had distant metastasis with an undetectable serum PSA. CONCLUSIONS: Disease can recur after radical prostatectomy even after an extended biochemical disease-free interval. None of the 1,916 men followed for an average of greater than 5 years after surgery had local recurrence or distant metastasis with an undetectable serum PSA. Based on these observations, we recommend no further evaluation, that is digital rectal examination or imaging studies, in men with an undetectable PSA following radical prostatectomy.     

ACCURACY OF PREDICTING LONG-TERM PROSTATE SPECIFIC ANTIGEN OUTCOME BASED ON EARLY PROSTATE SPECIFIC ANTIGEN RECURRENCE RESULTS AFTER RADICAL PROSTATECTOMY

PURPOSE: We determined how prostate specific antigen (PSA) doubling time changed with time and whether an early measure of doubling time would accurately predict long-term PSA values and clinical outcome in a cohort of patients followed expectantly after radical prostatectomy. MATERIALS AND METHODS: We analyzed data on 121 patients with PSA recurrence after radical retropubic prostatectomy. Group and individual analyses were performed on 60 patients who met study inclusion criteria. PSA doubling time was calculated and a curve was plotted using logarithmic transformation with linear regression and least squares analysis. In analysis 1 patients were placed into 3 subgroups according to doubling time. Doubling time was calculated per subgroup and the slopes of the aggregate curves were compared to determine how doubling time changed with time. In analysis 2 we calculated early doubling time per patient using only the initial 2 detectable PSA values and compared it with eventual doubling time in each using all PSA values. In addition, we analyzed how doubling time correlated with the clinical course. RESULTS: Using the group methodology there was no statistically significant acceleration or deceleration with time in doubling time slope in any of the 3 subgroups. On individual analysis we noted a weak correlation of early with eventual doubling time (correlation coefficient 0.69, p = 0.01). In 88% of patients eventual doubling time was not within 10% of early doubling time. Metastasis developed in 60% of patients with an eventual DT of 0 to 6 months, while 80% with an eventual doubling time of 6 to 12 months had no evidence of local or metastatic disease. No patients with an eventual doubling time of greater than 12 months have had metastatic disease and only 4 (16%) had local recurrence, which was treated with radiation therapy. In 8 of the 14 patients (23%) with local recurrence or metastatic disease early doubling time predicted eventual doubling time. Early doubling time was more rapid and slower than eventual doubling time in 5 and 1, respectively, of the remaining cases, which would have placed them in a different subgroup. CONCLUSIONS: On group analysis PSA doubling time appeared to be constant with time and there was no evidence that it accelerated with time in our dataset of PSA recurrence after radical prostatectomy. On individual analysis early doubling time showed a weak but statistically significant correlation with eventual doubling time. However, there was significant inaccuracy when predicting PSA doubling time based on early PSA values in individuals. Generally early projections of doubling time tend to over predict tumor biological aggressiveness, that is local recurrence or metastasis. A need remains for more accurate predictors of the rate of disease progression at initial PSA recurrence to determine accurately early in the clinical course the patients who may benefit from additional therapy. Currently no patient in our study has died of prostate cancer.     

VALIDITY OF THE PROSTATE SPECIFIC ANTIGEN TEST FOR PROSTATE CANCER SCREENING: FOLLOWUP STUDY WITH A BANK OF 21,000 SERA IN FINLAND

PURPOSE: We investigate the validity of prostate specific antigen (PSA) as a screening test for prostate cancer. MATERIALS AND METHODS: A registry of serum samples drawn from 1968 to 1976 from 21,387 men was linked to the Finnish Cancer Registry. During followup from 1968 to 1991, 104 prostate cancers were identified. A matched case control design with incidence density sampling and nested in the serum sample bank was applied, and PSA was assessed. RESULTS: The estimated sensitivity of the test was 44% and specificity 94% at a cutoff of 4.0 microg./l. in the total material. The sensitivity had improved to 86% in patients diagnosed in 5 years after the sample drawing. The test had a better sensitivity (93%) and specificity (96%) in men younger than 65 years at the time of the sample drawing compared to those older. The sensitivity further improved to 100% with a cutoff of 2.5 microg./l. CONCLUSIONS: PSA is a valid screening test for prostate cancer, which compares favorably with mammography for breast cancer. However, until an effect on mortality has been shown, routine screening cannot be recommended.     

ROLE OF EARLY ADJUVANT HORMONAL THERAPY AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER

PURPOSE: Recent prospective randomized studies have shown that adjuvant hormonal therapy combined with local treatment can significantly improve overall survival in patients with locally advanced disease. This finding challenges the previous belief that adjuvant hormonal therapy may not be beneficial for minimal stages TxN + M0 or less prostate cancer, particularly when combined with local treatment. We reviewed the benefits of adjuvant hormonal therapy in patients at risk for disease progression, especially when administered after radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the current literature and evaluated clinical information on stage pT3b cancer from a large single institution prostate cancer database to determine the current role of adjuvant hormonal therapy after radical prostatectomy for prostate cancer. RESULTS: Retrospective experimental and clinical studies have proved the impact of adjuvant hormonal therapy for decreasing prostate specific antigen (PSA) and clinical disease progression in patients with regionally limited prostatic cancer. This finding applies to stage pT3b as well as to lymph node positive cancer. Our literature review and current data from the Mayo Clinic database show that adjuvant hormonal therapy after prostatectomy has a significant impact on prostate specific antigen (PSA) progression but it also decreases systemic progression and cause specific death in patients with stage pT3b and lymph node positive disease. After adjusting for preoperative PSA, margins, grade, ploidy and patient age the risk ratio for stage pT3b disease in 707 cases was 0.3 (95% confidence interval 0.2 to 0.7). A recent prospective randomized trial showed a significant decrease in cancer death in N+ cases when adjuvant hormonal therapy was administered after radical prostatectomy, supporting previous Mayo Clinic data on N+ disease that favors combination therapy. In the PSA era, that is 1987 and after, our database data on stage pTxN+ cancer indicates that radical prostatectomy and hormonal therapy for single node positive disease resulted in 94% 10-year cause specific survival, which was not significantly different from the rate in patients with N0 disease after adjusting for local stage, Gleason grade, margins, ploidy, PSA and adjuvant hormonal therapy. CONCLUSIONS: Our literature review, including prospective randomized studies, and more recent results in the PSA era from our database indicate that early adjuvant hormonal therapy has a significant impact on time to progression and cause specific survival in patients with seminal vesicle invasion and limited lymph node disease who undergo radical prostatectomy, although in a retrospective nonrandomized study. Future prospective studies with longer followup are needed to evaluate the potential benefit of adjuvant treatment in regard to survival for stages pT2 and pT3a disease with unfavorable pathological variables.     

PREDICTION OF POST-RADICAL PROSTATECTOMY PATHOLOGICAL OUTCOME FOR STAGE T1c PROSTATE CANCER WITH PERCENT FREE PROSTATE SPECIFIC ANTIGEN: A PROSPECTIVE MULTICENTER CLINICAL TRIAL

PURPOSE: Prostate specific antigen (PSA) exists in bound (complexed) and unbound (free) forms in serum. The percentage of free PSA enhances the specificity of PSA testing for prostate cancer detection. We evaluated the use of percent free PSA preoperatively to predict pathological stage. MATERIALS AND METHODS: A total of 379 men with prostate cancer and 394 with benign prostatic disease 50 to 75 years old were enrolled in this prospective study at 7 medical centers. All subjects had a palpably benign prostate gland, serum PSA 4.0 to 10.0 ng./ml. and a histologically confirmed diagnosis. The Hybritech Tandem PSA and free PSA assays were used. Of the 379 cancer patients 268 (71%) underwent radical prostatectomy. RESULTS: Higher percent free PSA levels were associated with more favorable histopathological findings in prostatectomy specimens. A value of 15% free PSA provided the greatest discrimination in predicting favorable pathological outcome. Organ confined cancer, Gleason sum less than 7 and small tumors (10% or less involvement of the prostate) were noted in 75% of patients with greater than 15% and only 34% with 15% or less free PSA (p<0.001). Multivariate logistic regression analysis revealed percent free PSA to be the strongest predictor of postoperative pathological outcome (odds ratio 2.25), followed by biopsy Gleason sum (2.06) and patient age (1.35). Total PSA was not predictive in this cohort but has been shown in prior studies to be predictive of outcome when a broader range of PSA values is evaluated. CONCLUSIONS: Percent free PSA may be used for risk assessment of the presence (diagnosis) and stage of prostate cancer in men with PSA between 4 and 10 ng./ml. Percent free PSA may be combined with PSA, digital rectal examination and biopsy findings to help predict postoperative pathological stage and grade, and may assist the patient and physician in making more informed treatment decisions.     

PREDICTING PROSTATE SPECIFIC ANTIGEN OUTCOME PREOPERATIVELY IN THE PROSTATE SPECIFIC ANTIGEN ERA

PURPOSE: We evaluated the ability of previously defined risk groups to predict prostate specific antigen (PSA) outcome 10 years after radical prostatectomy in patients diagnosed with clinically localized prostate cancer during the PSA era. MATERIALS AND METHODS: Between 1989 and 2000, 2,127 men with clinically localized prostate cancer underwent radical prostatectomy, including 1,027 at Hospital of the University of Pennsylvania (study cohort) and 1,100 at Brigham and Women's Hospital (validation cohort). Cox regression analysis was done to calculate the relative risk of PSA failure with the 95% confidence interval (CI) in patients at intermediate and high versus low risk. The Kaplan-Meier actuarial method was used to estimate PSA outcome 10 years after radical prostatectomy. RESULTS: Compared with low risk patients (stages T1c to 2a disease, PSA 10 ng./ml. or less and Gleason score 6 or less) the relative risk of PSA failure in those at intermediate (stage T2b disease or PSA greater than 10 to 20 ng./ml. or less, or Gleason score 7) and high (stage T2c disease, or PSA greater than 20 ng./ml. or Gleason score 8 or greater) risk was 3.8 (95% CI 2.6 to 5.7) and 9.6 (95% CI 6.6 to 13.9) in the study cohort, and 3.3 (95% CI 2.3 to 4.8) and 6.3 (95% CI 4.3 to 9.4) in the validation cohort. The 10-year PSA failure-free survival rate in the 1,020 patients in the low, 693 in the intermediate and 414 in the high risk groups was 83%, 46% and 29%, respectively (p <0.0001). CONCLUSIONS: Based on 10-year actuarial estimates of PSA outcome after radical prostatectomy 3 groups of patients were identified using preoperative PSA, biopsy Gleason score and 1992 clinical T category.     

LAPAROSCOPIC RADICAL PROSTATECTOMY WITH THE HEILBRONN TECHNIQUE: AN ANALYSIS OF THE FIRST 180 CASES

PURPOSE: In 1998 Guillonneau and Vallancien introduced laparoscopic radical prostatectomy with primary access to the seminal vesicle. In 1999 we developed a different laparoscopic technique similar to the classic retropubic radical prostatectomy. We focus on early results and the learning curve of the procedure in the first 180 patients. MATERIALS AND METHODS: A transperitoneal approach is used with immediate access to Retzius' space. After the dorsal vein complex is endoscopically sutured, the urethra is incised and distal pedicles of the prostate with or without the neurovascular bundle transected. The apex is then pulled ventrally followed with incision at the bladder neck, and transvesical access to vas deferens and seminal vesicle. After completing the posterior wall of the urethrovesical anastomosis with 5 interrupted endoscopic sutures, the Foley catheter is placed, bladder neck closed and specimen extracted via the umbilical incision. From March 1999 to December 2000 we have performed 180 procedures, including 3 for stage pT1 tumor, 88 pT2, 82 pT3 and 7 pT4. Mean preoperative PSA was 13.3 ng./ml. (range 1.4 to 148), mean specimen weight 37.4 gm. (10 to 125) and median Gleason score 6 (3 to 9). For evaluation of the learning curve a separate analysis of 3 groups with 60 patients in each was done. Differences between groups 1 (first 60 patients) and 3 (last 60) were analyzed for statistically significant differences. RESULTS: Mean operating time was 271 minutes (range 150 to 500) and transfusion rate 31%. The reintervention rate was 4.4% and complication rate 18.8%. Of the patients 92% did not require any analgesia on postoperative day 2. Positive margins were found in 16% of the patients. The rate of positive margins in pT2 tumors was 2.3%, pT3a 15% and pT3b 34%. After a median followup of 12 months (range 3 to 23) in 9 (5%) patients a prostate specific antigen relapse was observed. The anastomosis was tight after removal of the catheter in 83% of patients, with a median time of 7 days (range 5 to 30). An anastomotic stricture had to be treated with laser incision in 3.3% of patients. On discharge from the hospital 33% of patients were continent, after 6 months 74% and after 12 months 97%. Analysis of the learning curve revealed significant differences in operating time (324 versus 265 minutes), conversion rate to open surgery (8.1% versus 1.7%), complication rate (23.3% versus 11.7%) and rate of prolonged catheterization (31.6% versus 10%, respectively), whereas the percentage of positive margins and continence rates showed no influence. CONCLUSIONS: Laparoscopic radical prostatectomy requires significant laparoscopic expertise with an ongoing learning curve. Morbidity is low, oncological control similar to results of open surgery and functional results are promising. The procedure should be performed only at dedicated centers with adequate training and expertise.     

SERUM HETEROPHILE ANTIBODIES INTERFERE WITH PROSTATE SPECIFIC ANTIGEN TEST AND RESULT IN OVER TREATMENT IN A PATIENT WITH PROSTATE CANCER

PURPOSE: We evaluated how naturally occurring heterophile antibodies in patient serum interfered with prostate specific antigen (PSA) immunoassay, resulting in over treatment for prostate cancer. MATERIALS AND METHODS: Serum samples were treated with heterophilic blocking reagent (Scantibodies Laboratory, Inc., Santee, California). Treated and untreated samples were tested by the Medics (Tosoh, Foster City, California ) Tandem-R (Beckman-Coulter Inc., Chaska, Minnesota) and Elecsys (Roche Molecular Biochemical, Indianapolis, Indiana) PSA assays. Heterophile antibodies were measured directly in treated and untreated samples by the human anti-mouse antibody immunoradiometric assay and heterophilic antibody identification enzyme immunoassay (Scantibodies Laboratories, Inc.). RESULTS: Human anti-mouse Ig heterophile antibodies in patient serum caused false-positive PSA test findings after radical prostatectomy, resulting in over treatment for presumed disease recurrence. CONCLUSIONS: If PSA is detectable after radical prostatectomy and the likelihood of incomplete resection or systemic disease is low, the presence of heterophile antibodies should be considered.     

HEALTH RELATED QUALITY OF LIFE DIFFERENCES BETWEEN BLACK AND WHITE MEN WITH PROSTATE CANCER: DATA FROM THE CANCER OF THE PROSTATE STRATEGIC UROLOGIC RESEARCH ENDEAVOR

PURPOSE: Understanding the potential consequences of racial differences in prostate cancer outcomes, from survival rates to quality of life considerations, is important for the clinician and patient. We examined demographic, clinical and health related quality of life data comparing black with white patients just after treatment of prostate cancer and 1 year later. MATERIALS AND METHODS: We analyzed data on 1,178 patients who were newly diagnosed with prostate cancer in the Cancer of the Prostate Strategic Urologic Research Endeavor, a national observational database of men recruited from 35 community and academic urology practices throughout the United States. Patient demographics, clinical characteristics and validated health related quality of life questionnaires were reviewed. A total of 958 white and 161 black patients with prostate cancer who completed at least 2 surveys were compared. RESULTS: The black patients were younger, and had lower income and education levels than white patients. Controlling for age, education and income differences, black patients generally had worse clinical characteristics at presentation and lower baseline health related quality of life data scores in most generic and disease specific categories at treatment. The most notable exception was sexual function, which was the only score that was higher in black patients at treatment. With time, health related quality of life improved in both groups but black patients had slower rates of improvement for general health, bodily pain, physical function, role function, disease worry and bowel function. They continued to have higher sexual function. CONCLUSIONS: Significant differences exist in clinical presentation, sociodemographic characteristics, and health related quality of life between black and white men with prostate cancer. These health related quality of life differences remain after treatment. Physicians should not assume that outcomes in black men would be similar to other patients.     

SERIAL PROSTATE SPECIFIC ANTIGEN, FREE-TO-TOTAL PROSTATE SPECIFIC ANTIGEN RATIO AND COMPLEXED PROSTATE SPECIFIC ANTIGEN FOR THE DIAGNOSIS OF PROSTATE CANCER

Purpose: The free-to-total prostate specific antigen (PSA) ratio and complexed PSA have been introduced as adjuncts to total PSA for prostate cancer screening. Little data exist on the use of these tests for serial PSA screening. We compared serial total PSA, the free-to-total PSA ratio and calculated complexed PSA in men diagnosed with prostate cancer and matched controls in a population based study.Materials and Methods: We identified 90 men diagnosed with prostate cancer between 1988 and 1996 with at least 3 serial serum samples obtained at 2-year intervals who were participants in the beta-Carotene and Retinol Efficacy Trial for the prevention of lung cancer. Samples were available up to 10 years before diagnosis. A total of 90 age matched men from the same cohort without prostate carcinoma were identified as controls. Free and total PSA was measured by the Abbott AxSYM system.Results: Baseline demographics of cases and controls were similar. At baseline and diagnosis the men with prostate cancer had higher total and complexed PSA, and a lower free-to-total PSA ratio than controls. Mean followup was 5.2 years in cases and 5.5 in controls. The yearly change in PSA parameters in cases versus controls was 20.7% versus 3.5% for total, -3.4% versus 0.2% for free-to-total and 21.5% versus 3.4% for complexed PSA (p <0.0001). At diagnosis PSA alone was estimated to perform with more than 90% specificity in our model.Conclusions: In this population based study total PSA was superior to the free-to-total PSA ratio for predicting the development of prostate cancer. While serial changes in free-to-total PSA ratios with time were statistically significantly different in men diagnosed with prostate cancer and controls, the magnitude of these serial changes were slight enough to render them clinically insignificant.     

CLASSIFICATION OF LOCALIZED UNTREATED PROSTATE CANCER BASED ON 791 MEN TREATED ONLY WITH RADICAL PROSTATECTOMY: COMMON GROUND FOR THERAPEUTIC TRIALS AND TNM SUBGROUPS

Purpose

We examined cancer volume, percent Gleason grade 4/5 cancer, cancer location (peripheral versus transition zone), capsular penetration and biochemical cure rates in men undergoing radical prostatectomy to determine differences among clinical stages T1c, T2a, T2b and T2c.

Materials and Methods

Detailed chart reviews confirmed the precise clinical stages assigned to 791 consecutive men treated only with radical prostatectomy. All prostates were examined prospectively by the Stanford technique of 3 mm. step sections. For biochemical cure rates a subset of 366 men were followed for a minimum of 5 years. Failure was defined as prostate specific antigen Tosoh [dagger] 0.07 ng./ml. or greater and rising. T1c was defined as impalpable cancer.[dagger] TOSOH Medics, Foster City, California.

Results

T1c and T2a stages had half as much cancer volume as T2b and T2c cancers, 10 versus 25% Gleason grade 4/5 and half as much capsular penetration (30 versus 61%). Biochemical cure rates were 70 and 72% for T1c and T2a compared to 37 and 27% for T2b and T2c, respectively. Of T1c cancers 25% were in the transition zone compared to 7.9 to 9.9% of T2a to c cancers.

Conclusions

T1c cancers are similar to T2a cancers in tumor volume and percent Gleason grade 4/5, the primary determinants of therapeutic failure. Minimal 5-year cure rates for T1c and T2a cancers are similar. Transition zone cancers are 2.5 times more common in T1c cancers than in palpable T2 tumors. T2a cancers like T1c cancers are highly favorable tumors and should be retained in TNM classifications. These data suggest that the 4 clinical stages of T1c to T2c can serve as a valid basis for comparing different therapeutic strategies.     

TREATMENT FOR BENIGN PROSTATIC HYPERPLASIA AMONG COMMUNITY DWELLING MEN: THE OLMSTED COUNTY STUDY OF URINARY SYMPTOMS AND HEALTH STATUS

PURPOSE: We describe treatments for benign prostatic hyperplasia (BPH) among men participating in the Olmsted County study of urinary symptoms and health status among men during 10,000 person-years of followup. MATERIALS AND METHODS: A cohort of 2,115 men 40 to 79 years old was randomly selected from an enumeration of the Olmsted County, Minnesota population (55% response rate). Participants completed a previously validated baseline questionnaire to assess symptom severity and voided into a portable urometer. A 25% random subsample underwent transrectal sonographic imaging of the prostate to determine prostate volume and measurement of serum prostate specific antigen. Followup included retrospective review of community medical records and completion of a biennial questionnaire to determine the occurrence of medical and surgical treatment for BPH in the subsequent 6 years. RESULTS: During more than 10,000 person-years of followup 167 men were treated, yielding an overall incidence of 16.0/1,000 person-years. There was a strong age related increase in risk of any treatment from 3.3/1,000 person-years for men 40 to 49 years old to more than 30/1,000 person-years for those 70 years old or older. Men with moderate to severe symptoms (American Urological Association symptom index greater than 7), depressed peak urinary flow rates (less than 12 ml. per second), enlarged prostate (greater than 30 ml.) or elevated serum prostate specific antigen (1.4 ng./ml. or greater) had about 4 times the risk of BPH treatment than those who did not. After adjustment for all measures simultaneously an enlarged prostate (hazard ratio 2.3, 95% confidence interval [CI] 1.1, 4.7), depressed peak flow rate (hazard ratio 2.7, 95% CI 1.4, 5.3) and moderate to severe symptoms (hazard ratio 5.3, 95% CI 2.5, 11.1) at baseline each independently predicted subsequent treatment. CONCLUSIONS: While repeat contact and availability of urological measurements during the study period may have influenced treatment decisions in this cohort, the data demonstrate that treatment is common in elderly men with nearly 1 in 4 receiving treatment in the eighth decade of life. Furthermore, these data suggest that men with moderate to severe lower urinary tract symptoms, impaired flow rates or enlarged prostates are more likely to undergo treatment, with increases in risk of similar magnitude to those associated with adverse outcomes, such as acute urinary retention.