Results of transrectal ultrasound-guided biopsies and clinical significance of Japanese prostate cancer

BACKGROUND: We review the outcomes of ultrasound-guided biopsy in consecutive patients and assess clinical significance of Japanese prostate cancer. METHODS: Examination was made of 1469 patients subsequent to transrectal ultrasound-guided biopsy of the prostate gland. For 84 patients, two or more sets of ultrasound-guided biopsies were conducted following the initial negative results during this period. Two hundred and thirty-two patients with benign histology at the initial biopsy underwent transurethral resection of the prostate (TURP). The clinical significance of the cancers was assessed based on patient age and calculated tumor volume at diagnosis, assumed cancer volume doubling time and life-expectancy in the Japanese male population. RESULTS: Overall, 327 of the 1469 patients (22.3%) had prostate carcinoma. Positive biopsy rates in patients with PSA 2.0 ng/ml or lower, 2.1-4.0 ng/ml, 4.1-10.0 ng/ml and 10.1 ng/ml or greater were 4.6%, 8.6%, 15.8% and 59.5%, respectively. Of the 232 patients who underwent TURP, 15 (6.5%) had cancer. Of the 84 patients subjected to the multiple sets of biopsies, 19 (22.6%) cancers were detected. Of the 203 cancers without distant metastasis at initial biopsy, 13.3%, 25.1%, 32.5% and 40.4% of tumors for 2-, 3-, 4- and 6-year tumor doubling times gave no indication of clinical significance. Nearly half these patients (43-52%) had clinical stage T1c disease. The estimated proportion of clinically insignificant tumors in repeat biopsy was virtually the same as first set biopsies. CONCLUSIONS: Low PSA was not necessarily an indication of indolent cancer and repeat biopsy did not often demonstrate clinically unimportant cancers. Many patients with stage T1c disease may eventually prove to require no treatment.     

Autonomic neuropathy: clinical and instrumental findings

A good staging system should be able to accurately reflect the natural history of a malignant disease, to express the extent of the disease at the time of diagnosis, and stratify patients in prognostically distinctive groups. The staging system for prostate cancer, as it is today, fails to fulfill these requirements. Approximately one third of the patients who undergo surgery for complete excision of prostate cancer in fact do not have a localize disease. The incidence of tumor at the inked margin may reach 30% for T1 stage and up to 60% for clinical T2b prostate cancer according to comparison with pathologic examination of resected specimen. Several concepts have been recently proposed as a means of improving the accuracy of the available staging system. In this paper, we review current aspects of clinical and pathological staging of prostate cancer, and the importance of these new concepts on the early stages of prostate cancer.     

Transurethral needle ablation of the prostate: a minimally invasive treatment for symptomatic benign prostatic hyperplasia

Transurethral needle ablation of the prostate, a relatively new minimally invasive treatment modality for patients with bladder outlet obstruction attributable to an enlarged prostate gland, has undergone extensive evaluation by numerous investigators worldwide. The results to date indicate that needle ablation is safe and effective for relieving symptoms in patients with benign prostatic hyperplasia, and the effect has been demonstrated to be durable for at least 2 years. Nevertheless, additional investigations with longer follow-up data are needed to address the important issues of extended durability (5 to 10 years) and biophysiologic mechanism of action. Comparisons between transurethral needle ablation of the prostate and transurethral resection of the prostate (TURP) have revealed that the subjective and objective measures of response are comparable, although TURP has consistently displayed a slight advantage over needle ablation for most variables analyzed, except quality of life score. The advantages of needle ablation over TURP are (1) performance in the office as an outpatient procedure, (2) no need for general or spinal anesthesia, (3) rapid recovery, (4) minimal side effects, and (5) one-time intervention. The following disadvantages exist with needle ablation: (1) it may not be indicated or effective in patients with large prostate glands (75 g or more); (2) no prostate tissue is available for histologic evaluation; and (3) no long-term efficacy or re-treatment rate data have been published. Overall, the available information indicates that transurethral needle ablation is a viable minimally invasive treatment that may be applicable in men with moderate to severe bladder outlet obstruction as a result of an enlarged prostate gland.     

Low risk of urinary incontinence following prostate brachytherapy in patients with a prior transurethral prostate resection

PURPOSE: To review post implant morbidity in patients with prior transurethral prostate resection (TURP). METHODS AND MATERIALS: Nineteen patients with stage T1-T2 prostatic carcinoma and prior TURP were treated with I-125 or Pd-103 implantation from 1991 through 1994. Follow-up ranged from 1 to 6 years (median: 3 years). The time from TURP to implantation ranged from 2 months to 15 years (median: 3 years). RESULTS: Only one patient developed mild urinary stress incontinence, 6 months following his I-125 implant. The actuarial freedom from permanent urinary incontinence at 3 years after implantation was 94%. No patient required urethral dilatation for urethral stricture. Eleven patients were sexually potent prior to implantation. At 3 years after treatment, all patients had maintained potency. CONCLUSION: In our experience, there has been remarkably little adverse sequelae following I-125 or Pd-103 implantation in patients with a prior history of TURP.     

Can insignificant prostate cancer be predicted preoperatively in men with stage T1 disease?

This study reviews the pathological findings in nonpalpable prostate cancer detected on transurethral resection (TUR) (stages T1a and T1b) and on needle biopsy (stage T1c) to determine whether insignificant cancers can be predicted preoperatively. The majority of stage T1a cancers are insignificant and all stage T1b cancers are significant. Preoperative pathological parameters cannot identify the minority of T1a cancers that are more significant and the minority of T1b cancers with relatively little residual cancer. Although most nonpalpable tumors diagnosed by screening techniques are usually significant tumors, which would be treated aggressively if they were palpable, 12% to 26% of cancers removed from nonpalpable disease are relatively insignificant. There is conflicting data as to whether a combination of needle biopsy findings and PSA density measurements can aid in the prediction of insignificant cancers. If conservative management is considered, a patient should undergo repeat biopsies (including transition zone biopsies) to detect those more significant cancers that may have been undersampled. In addition, serial serum PSA measurements should be performed to detect whether serum PSA levels increase to a point where these tumors would be reclassified as significant. When planning therapy for T1 patients, the age, comorbidity, and treatment preferences of the patient are key factors that must also be taken into account.     

Experience with radical prostatectomy as treatment of localized cancer of the prostate at the Fundación Santa Fe de Bogotá, Colombia

OBJECTIVE: To analyze the experience of the Fundación Santa Fe de Bogotá with radical prostatectomy in the treatment of localized prostatic cancer. METHODS: A retrospective study was conducted on 108 patients with localized carcinoma of the prostate stage T1-T2NxM0 submitted to radical prostatectomy from 1989 to 1994. RESULTS: Preoperatively, 50% of the patients had a PSA < 10 ng/ml and 14% had values that fell within the normal ranges of 0-4 mg/ml. A family history of prostate cancer was detected in 9.3% of the patients. The prostate cancer was clinically understaged in 75% of the patients, particularly those with stages T2a and T2b, and less significantly in those with stage T2c. Considering only those patients in whom the pathological staging had disclosed the cancer was not localized, this incidence accounted for 52% (n = 57). The presence of surgical margins was approximately 36%. The tumor recurrence rate was 26.9% and the complication rate was 6.8%. CONCLUSION: The relatively low complication rate in the present series shows that radical prostatectomy is a safe procedure that achieves good results if the cases are carefully selected and the diagnostic test are widely utilized.     

Prostate cancer: local staging with endorectal magnetic resonance imaging

BACKGROUND: Prostate cancer has received increasing attention during the past decades. Staging of tumors before treatment is imperative for planning appropriate therapy. The purpose of this study is to assess the role of endorectal magnetic resonance imaging (MRI) in local staging of prostate cancer. METHODS: Endorectal MRI was performed in 31 patients with histologically-proven prostate cancer. MRI was done three to 100 days (mean, 32.1 days) after either transrectal ultrasonography (TRUS) with biopsy or transurethral resection of the prostate (TURP). Radical prostatectomies were performed within two weeks after MRI. The diagnostic accuracy of endorectal MRI for local tumor staging, specifically for extracapsular extension (ECE) and seminal vesicle invasion (SVI), was evaluated by correlating MRI results with histopathologic findings of whole-mount specimens. RESULTS: The accuracy of endorectal MRI for the detection of tumor presence and estimation of tumor volume was 48%. Sensitivity, specificity and positive predictive value for evaluation of ECE were 88%, 69% and 80%, respectively, and for SVI, were 66%, 84% and 50%, respectively. The overall accuracy of MRI in local tumor staging (using the TMN system) was 61%. Accuracy in differentiating localized from invasive cancer was 84%. CONCLUSION: Endorectal MRI is not accurate enough to detect tumor presence or estimate tumor volume. Diagnostic accuracy for local tumor staging is unsatisfactory. However, endorectal MRI is highly accurate in differentiating localized (stage B) from invasive (stage C) cancer.     

Outcome based staging for clinically localized adenocarcinoma of the prostate

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.     

Extraorganic hepatic artery aneurysm: failure of transcatheter embolization

BACKGROUND: We evaluated the safety and efficacy of transurethral electrovaporization of the prostate (TVP) as a new alternative treatment for patients with benign prostatic hyperplasia. METHODS: A total of 22 patients with symptomatic benign prostatic hyperplasia, including 4 with urinary retention, underwent TVP. If enough of a cavity was not created after 60 minutes of vaporization, transurethral resection of the prostate (TURP) was performed successively. International Prostate Symptom Score (I-PSS) with quality-of-life index, maximum flow rate, and postvoid residual volume were measured at baseline and at 2 weeks, 1, 3, and 6 months. A pressure-flow study was performed at baseline and at 3 or 6 months after surgery. RESULTS: TURP was required in 10 of 22 patients. At 6 months, mean I-PSS decreased from 20.0 to 5.2, quality-of-life index decreased from 4.6 to 1.1, mean maximum flow rate increased from 6.9 to 16.7 mL/s, and postvoid residual volume decreased from 152 to 32 mL. Detrusor pressure at maximum flow decreased from 108 to 39 cm H2O, with a significant relief of bladder outlet obstruction in 93% of the patients. Mean decrease in hematocrit was 4.4%, and in serum sodium, 4.8 mEq/L. None of the patients required transfusions or had TUR syndrome. A urethral stricture and a severe stress incontinence developed in 1 patient. CONCLUSION: TVP seems to be a safe and effective alternative to a standard TURP associated with fewer intraoperative complications. Although preliminary clinical results have been promising, further study is necessary to establish long-term efficacy and safety of this procedure.     

Analyzing outcome-based staging for clinically localized adenocarcinoma of the prostate

BACKGROUND: A clinical staging system based on the prostate-specific antigen (PSA) and the calculated prostate carcinoma volume (cVCa) construct previously has been proposed. This study was performed to assess whether this proposed clinical staging system was valid in an independent surgical and radiation data set in patients with clinically localized disease. METHODS: Cox regression multivariable analyses were used to assess the significance of staging systems (1992 American Joint Commission on Cancer Staging [AJCC] clinical and pathologic stage, versus cVCa-PSA clinical stage) to predict time to posttherapy PSA failure in 441 and 465 patients managed by surgery and radiation, respectively. Significant staging systems identified using Cox regression were tested further using established comparative measures to define the most clinically useful system. RESULTS: Both the 1992 AJCC pathologic stage and the cVCa-PSA clinical stage were significant predictors of time to postoperative PSA failure (P = 0.0001), whereas only the cVCa-PSA clinical stage was a significant predictor of time to postradiation PSA failure (P = 0.0001) using a Cox regression multivariable analysis. Further analyses using a pairwise comparison of the 1992 AJCC pathologic stage and cVCa-PSA clinical stage found the cVCa-PSA staging system provided a more clinically useful prediction of time to postoperative PSA failure. Specifically, the cVCa-PSA staging system was able to identify surgically managed patients with pathologic AJCC T2 disease who did poorly (3-year bNED = 22%) while also selecting patients with clinical AJCC T2b,c disease that was managed by radiation who did well (3-year bNED = 100%). CONCLUSIONS: A clinical staging system based on parameters obtained during the routine evaluation for AJCC clinical T1,2 prostate carcinoma provided a clinically useful stratification of both postoperative and postradiation PSA failure free survival.     

Immuno-hemolytic transfusion reactions. II Physiopathologic basis and diagnosis

Prostatic intraepthelial neoplasia (PIN) is a putative premalignant change that bears a morphological similarity to prostatic cancer and shows increased frequency, severity, and extent in patients with prostate cancer. This article discusses the evidence for PIN as a premalignant lesion, reviews the morphology, terminology, appropriate grading system, and diagnostic significance of PIN, as well as describes management recommendations for further evaluation when PIN is diagnosed in prostate resection and biopsy specimens. Clinical management of high-grade PIN found in transurethral resection of the prostate (TURP) or prostate biopsy specimens should include repeat transrectal ultrasound (TRUS) and prostate biopsy for early detection of prevalent coexistent prostate cancer. In cases of high-grade PIN, increased surveillance methods have the potential to decrease morbidity and mortality by early cancer diagnosis.     

Enterocolitis after the surgical treatment of Hirschsprung''s disease: risk factors and financial impact

OBJECTIVE: To determine whether anterograde ejaculation is preserved after transurethral resection of both the prostate and bladder neck (TURP and TURBN). PATIENTS AND METHODS: Between 1994 and 1997, 45 patients (mean age 53.2 years, range 42-62) with bladder neck obstruction and small obstructive adenomas (< 35 g) underwent TURP/TURBN, preserving part of the supramontanal prostate and prostatic urethra for > 1 cm from the verumontanum. They were assessed before and after 0.5-2 years to determine the type of ejaculation, symptom scores and sexual function, and compared with 10 similar patients who had undergone a conventional TURP. RESULTS: With preservation of > 1 cm of the supramontanal prostate, anterograde ejaculation was maintained in 80% of the patients, whereas only one patient in the control group retained anterograde ejaculation. CONCLUSIONS: The preservation of anterograde ejaculation after TURP (in approximately 20% of cases) and after transurethral incision of the prostate (> 90% cases) reported in the literature probably relates more to the presence of an adequate amount of residual prostatic tissue than to the existence of a hypothetical 'pre-prostatic sphincter'.     

Clinical staging of prostate cancer

Clinical staging of prostate cancer was reviewed on the basis of TNM classification edited by UICC in 1997. In this revision, (1) T1c was newly categorized among T1 for cases of high PSA level without any abnormal sign of DRE, (2) T2 was subdivided into T2a and T2b in accordance with unilateral or bilateral nodule in the prostate, respectively, (3) T3 was also subdivided into T3a with capsular invasion and T3b with seminal vesicle invasion. It is hoped that present classification will become useful tools for the detection of the tumor burden cancer patients.     

Unusual structural stability and ligand induced alterations in oligomerization of a galectin

OBJECTIVE: To evaluate the balloon-occluded arterial infusion (BOAI) of cisplatin and adriamycin as a preoperative adjuvant chemotherapy in patients with bladder cancer of stage > or = T2 or in those with stage T1 and multiple large tumours. PATIENTS AND METHODS: The study comprised 120 patients with bladder cancer who underwent BOAI from November 1984 to December 1995. BOAI chemotherapy (adriamycin and cisplatin) was administered under ischaemia through a 7 F torque-control balloon catheter, both sides of which were inserted into the contralateral internal iliac artery. The regression rate of tumours and any improvement in tumour stage was assessed. RESULTS: The clinical response rate (complete or partial) was 66% and the tumour stage improved in 39% of the patients after BOAI. Of 26 patients with stage T3 a diagnosed before BOAI, 12 were diagnosed as T2 or less after treatment. Of 27 patients who underwent total cystectomy because the tumour was diagnosed as T2 after BOAI, the post-operative histopathological examination showed that 22 (82%) were stage pT1 or below. The features associated with a good response to BOAI in patients with up to pT3a disease were grade 3, non-papillary tumours with a diameter of < 3 cm. CONCLUSION: In patients diagnosed as stage T2 and T3a, or stage T1 with multiple large tumours difficult to be treat by transurethral resection, BOAI should be considered as the first choice to decrease the stage or to confirm the pathological staging.     

Reduced space hidden Markov model training

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.     

Novel staging tool for localized prostate cancer: a pilot study using genetic adaptive neural networks

PURPOSE: An estimated $1.5 billion is spent annually for direct medical expenses and an additional $2.5 billion for indirect costs for the management of prostate cancer. Today there are several procedures for staging prostate cancer, including lymph node dissection. Despite these procedures, the accuracy of predicting extracapsular disease remains low (range 37 to 63, mean 45%). Use of multiple staging procedures adds significantly to the costs of managing prostate cancer. Recently artificial intelligence based neural networks have become available for medical applications. Unlike traditional statistical methods, these networks do not assume linearity or homogeneity of variance and, thus, they are more accurate for clinical data. We applied this concept to staging localized prostate cancer and devised an algorithm that can be used for prostate cancer staging. MATERIALS AND METHODS: Our study comprised 1,200 men with clinically organ confined prostate cancer who underwent preoperative staging using serum prostate specific antigen, systematic biopsy and Gleason scoring before radical prostatectomy and lymphadenectomy. The performance of the neural network was validated for a subset of patients and network predictions were compared with actual pathological stage. Mean patient age was 62.9 years, mean serum prostate specific antigen 8.1 ng./ml. and mean biopsy Gleason 6. Of the patients 55% had organ confined disease, 27% positive margins, 8% seminal vesicle involvement and 7% lymph node disease. Of margin positive patients 30% also had seminal vesicle involvement, while of seminal vesicle positive patients 50% also had positive margins. RESULTS: The sensitivity of the network was 81 to 100%, and specificity was 72 to 75% for various predictions of margin, seminal vesicle and lymph node involvement. The negative predictive values tended to be relatively high for all 3 features (range 92 to 100%). The neural network missed only 8% of patients with margin positive disease, and 2% with lymph node and 0% with seminal vesicle involvement. CONCLUSIONS: Our study suggests that neural networks may be useful as an initial staging tool for detection of extracapsular extension in patients with clinically organ confined prostate cancer. These networks preclude unnecessary staging tests for 63% of patients with clinically organ confined prostate cancer.     

Neuroendocrine differentiation in prostatic carcinoma during hormonal treatment

OBJECTIVES: Neuroendocrine differentiation (NED) is a common feature in adenocarcinoma of the prostate. Several studies suggest that NED may have a major impact on cancer progression as neuroendocrine (NE) secretory products have been shown to possess growth stimulatory effects. NED has also been proposed to constitute part of the mechanism by which a prostate cancer cell progresses toward androgen independence as NE tumor cells have been demonstrated to be devoid of androgen receptor immunoreactivity. In this retrospective study, we evaluated NED status in prostate cancer specimens from patients undergoing androgen ablation therapy. METHODS: The degree of NED in transurethral resection of the prostate (TURP) samples from 53 patients with prostate cancer was investigated by immunocytochemistry using polyclonal rabbit immunoglobin G (IgG) against chromogranin A (CgA). Changes in NED with time were determined by a manual semiquantitative cell counting method. RESULTS: During androgen withdrawal therapy, 21 tumors (40%) displayed increased NED concomitant with histopathologic tumor progression, whereas 29 carcinomas (55%) showed no change in NED status. However, a majority of the histopathologically unchanged tumors displayed marked NED at the first TURP and an increase in NED was by definition not possible. In only 3 cases (5%) was a decrease in NED observed with time. CONCLUSIONS: Androgen ablation therapy may be a contributing factor to the increase in NED of prostatic adenocarcinoma with time, and our findings imply that androgen withdrawal therapy enhances the selection and progression of NED, androgen-independent tumor cells.     

Failure to void after transurethral resection of the prostate and mode of presentation

OBJECTIVES: Contemporary audits and reviews of outcome after transurethral resection of the prostate (TURP) make little reference to failure to void following catheter removal after this operation. There have been few reports of the likelihood of a successful trial without a catheter after TURP related to mode of presentation. We report the results of a retrospective review of outcome of TURP related to mode of presentation, age, and prostate histologic findings in a consecutive series of patients in a London Teaching Hospital. METHODS: A consecutive series of 379 patients (381 TURPs) was reviewed to document the incidence of and risk factors for failure to void following initial trial without a catheter after TURP. RESULTS: Twelve percent of men failed to void after TURP on the initial trial without a catheter. In those patients presenting with lower urinary tract symptoms, there were no instances of failure to void. Ten percent of patients with acute retention (painful inability to void, urine volume less than 800 mL), 38% with chronic retention (maintenance of spontaneous voiding, bladder volume greater than 500 mL), and 44% with acute on chronic retention (painful retention, urine volume greater than 800 mL) failed to void after TURP. Only 1% of patients required management by long-term catheterization. Failure to void on catheter removal was not related to age or prostate histologic findings. CONCLUSIONS: Bladder volume at initial presentation in patients with urinary retention provides important information about the likelihood of re-establishing spontaneous voiding catheter removal following TURP. Patients should be warned that there is a significant chance of failure to void after TURP, the exact risk depending on their mode of presentation, but that most will ultimately not require a permanent indwelling catheter.     

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% 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-toal 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% 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.