Diffraction and coherence in breast ultrasound tomography: a study with a toroidal array.

Ultrasound is commonly used as an adjunct to mammography for diagnostic evaluation of suspicions arising from breast cancer screening. As an alternative to conventional sonography that uses hand-held transducers, toroidal array probes that encircle the breast immersed in a water bath have been investigated for ultrasound tomography. In this paper, two sets of experiments performed with a prototype ultrasound scanner on a phantom and a human breast in vivo are used to investigate the effects of diffraction and coherence in ultrasound tomography. Reconstructions obtained with transmission diffraction tomography (TDT) are compared with conventional reflection imaging and computerized ultrasound tomography showing a substantial improvement. The in vivo tests demonstrate that TDT can image the complex boundary of a cancer mass and suggest that it can reveal the anatomy of milk ducts and Cooper's ligaments.

Cryoablation of benign breast tumors: evolution of technique and technology.

We report on improvements in cryoprobe design and techniques of cryoablation as a minimally invasive alternative to open surgery for the treatment of benign breast tumors. In the study, which was conducted in 12 centers, 124 lesions in 102 patients were monitored for a period of 12 months after cryoablation. Two different treatment techniques were used: Double HI FREEZE and Tailored Freeze. In patients treated with the Tailored Freeze technique significantly better results were recorded 12 months after the procedure: the median reduction in tumor volume was 91%, 73% of all tumors treated were nonpalpable, 84% of lesions less than 2.5 cm in maximum diameter were nonpalpable, and none of the 31 mammograms performed yielded abnormal findings. Patient satisfaction was good to excellent in 92% of the patients. The safety profile of this technique was excellent; all complications were minor. Evolution of cryoablation freezing techniques, coupled with improvements in cryoprobe design, has resulted in significant improvements in both safety and effectiveness.

Imaging and prostate cancer chemoprevention: Current diagnosis and future directions.

Identifying appropriate patients as targets for prostate cancer chemoprevention is a daunting task due to the multiple known and unknown factors contributing to patients' risk profiles. Confirmation of the extent and location of early prostate cancers, as well as prostatic intraepithelial neoplasia (PIN), also requires improved image guidance of biopsy to contain costs. Prostate-specific antigen (PSA) in conjunction with transrectal ultrasound (TRUS) and digital rectal examination (DRE) have been the front-line tests for early prostate cancer. Although advances in MRI continue to improve its accuracy, limited availability and higher costs preclude its widespread use for chemoprevention trials. Improved biopsy risk assessment has been achieved by categorizing TRUS grayscale and vascular findings for each biopsy region. In addition, concomitant suspicious TRUS findings also improved cancer yield per biopsy, as well as the amount and grade of tumor per core. However, TRUS remains operator dependent despite advancements in grayscale and vascular imaging. Additional risk parameters are needed to better localize small disease foci and improve the overall diagnostic performance while containing costs. Future work may improve the specificity of tissue characterization to produce reliable noninvasive biomarkers for monitoring chemoprevention responses of early prostate cancer or PIN.

Prostate cancer: the role of transrectal ultrasound and its impact on cancer detection and management.

With the advent of higher-frequency transducers as well as Doppler technologies, TRUS has become a valuable tool in the detection and management of prostate cancer. When combined with the other risk identifiers, an informed patient, and an experienced operator, it cannot only reduce the number of missed cancers by effective targeting of biopsies, but also reduce the number of unnecessary biopsies.

Patients with abnormal ultrasound of the prostate but normal digital rectal examination should be classified as having clinical stage T2 tumors.

PURPOSE: The current TNM staging system classifies prostate tumors with abnormal transrectal ultrasound but normal digital rectal examination as clinical stage T2. However, most urologists consider these tumors as clinical stage T1c due to the perceived inaccuracy of transrectal ultrasound in clinical staging. To determine the role of transrectal ultrasound in the clinical staging of prostate cancer we evaluated the pathological stage and disease-free survival of patients undergoing radical prostatectomy who had tumor detected by needle biopsy because of elevated serum prostate specific antigen with or without transrectal ultrasound abnormalities. MATERIALS AND METHODS: Between 1991 and 1996, 738 patients underwent radical retropubic prostatectomy as monotherapy for clinically localized prostate cancer. Patients were classified into group 1-normal digital rectal examination and transrectal ultrasound (138), group 2-normal digital rectal examination but abnormal transrectal ultrasound (366) and group 3 -abnormal digital rectal examination (234). We compared pathological parameters and disease-free-survival among the 3 groups. RESULTS: Tumors were organ confined in 61%, 42% and 41% of patients in groups 1, 2 and 3, respectively (p = 0.0001). Overall disease-free survival was 80% with a mean followup of 68 months. Disease recurred in 8%, 22% and 25% of patients in groups 1, 2 and 3, respectively (p = 0.007). Group 1 had better disease-free survival compared to groups 2 and 3 (p = 0.003 and p = 0.002, respectively), and there was no difference in disease-free survival between groups 2 and 3 (p = 0.39). CONCLUSIONS: We provide evidence to support the use of transrectal ultrasound findings in the clinical staging system for prostate cancer. Patients with normal digital rectal examination, elevated serum prostate specific antigen and abnormal transrectal ultrasound should be considered as having clinical stage T2 disease.

Vesicourethral anastomosis biopsy after radical prostatectomy: predictive value of prostate-specific antigen and pathologic stage.

OBJECTIVES: To assess the role of clinical parameters and pathologic stage in predicting a positive vesicourethral anastomosis (VUA) biopsy in patients with a rising prostate-specific antigen (PSA) level after radical prostatectomy. METHODS: Forty-five patients were referred for a rising PSA level after radical prostatectomy. Transrectal ultrasound evaluation included visualization of the VUA and VUA quadrant biopsies. The rate of positive biopsies (per core and per patient) was correlated with race, PSA level, and the radical prostatectomy pathologic stage. RESULTS: Overall, 53% of patients had a positive biopsy. In multivariate analysis, the dominant independent and synergistic clinical parameters determining positive biopsy rates were a PSA greater than 1 ng/mL at the time of biopsy and the pathologic stage (P = 0.04 and P = 0.02, respectively). Using a PSA cutoff point of 1.0 ng/mL, those patients with organ-confined disease and a PSA of 1.0 ng/mL or less showed no positive cancer cores (low-risk group). Conversely, 89% of patients with extraprostatic extension and a PSA greater than 1.0 ng/mL had a positive biopsy (P <0.01) (high-risk group). Patients with organ-confined disease and a PSA greater than 1.0 ng/mL or extraprostatic extension and a PSA 1.0 ng/mL or less (intermediate-risk group) had a significantly higher chance of having residual cancer than the low-risk group (P <0.025). CONCLUSIONS: The PSA level at the time of biopsy and the pathologic stage of the radical prostatectomy specimen were the strongest determinants of a positive biopsy. A combination of PSA and pathologic stage is useful for decisions regarding VUA biopsy. Patients with organ-confined disease and a PSA of 1.0 ng/mL or less do not appear to benefit from a VUA biopsy, and patients with extraprostatic extension and a PSA greater than 1.0 ng/mL have such a high probability (89%) of local recurrence at the VUA that biopsy may be unnecessary. It appears that VUA biopsy can be restricted to those patients with an intermediate risk (organ-confined disease with PSA greater than 1 ng/mL or extraprostatic extension with a PSA less than 1 ng/mL).

CT-monitored percutaneous cryoablation in a pig liver model: pilot study.

PURPOSE: To determine the safety and feasibility of percutaneous cryoablation with computed tomographic (CT) guidance in a pig liver model. MATERIALS AND METHODS: Nine angiographic balloons (mean diameter, 9 mm) were placed in the livers of seven domestic pigs (mean weight, 30.0 kg +/- 14.0 [SD]) as tumor-mimicking lesions. By using ultrasonographic and CT guidance, two 2.4- or 3.0-mm cryoprobes were placed flanking the balloon, and a 15-20-minute freezing process was performed. Hemostasis was achieved by placing absorbable cellulose fabric down the probe tract. After 24-96 hours, animals were sacrificed, and their livers were removed and were sectioned axially at 5-mm intervals for comparison with CT images. RESULTS: All animals survived the procedure without complication. No serious hemorrhage was found in any case. Ice balls were readily visualized at CT because they appeared as areas of decreased attenuation (1.0 HU +/- 20.7) when compared with areas of normal liver (48.2 HU +/- 6.3, P < .05). The mean ablative margin was 1.7 cm, and only one of nine cases, the one with probe failure, had a positive margin. Beam-hardening artifact from the metal probes was present but did not interfere with the procedure. Ice-ball size and shape corresponded closely to the area of necrosis determined at histopathologic analysis. CONCLUSION: CT-monitored percutaneous cryoablation is feasible and safe in this pig liver model.

Hepatic cryosurgery via minilaparotomy in a porcine model: an alternative to open cryosurgery.

BACKGROUND: Cryosurgery of liver lesions is becoming increasingly accepted for the ablation of liver tumors. Attempts at laparoscopic cryosurgery have been very limited and often need to be converted to open laparotomy due to the complexity of the procedure. METHODS: Seven domestic pigs were anesthetized, and 17 small (0.7 cm mean diameter) tumor mimicking agar "lesions" were percutaneously placed in the liver. Two small subcostal incisions ( approximately 2.0 cm) were placed, and an endocavitary ultrasound transducer (with a 2. 4-mm cryoprobe mounted on it) was placed on the liver surface. Lesions were localized and directly punctured with one or two cryoprobes under ultrasound guidance, and a single 15-min freeze was undertaken. The animals were then killed, and their livers were removed and serially sectioned. RESULTS: Total time for probe placement was approximately 10 min after incisions had been made. Animals tolerated the procedure well and all survived until they were killed. No intraabdominal complications were detected at exploration. Mean cryolesion dimensions were 3.0 cm (single probe) and 3.3 cm (dual probe) (p > 0.05). Positive margins were detected in one lesion treated with a single probe, and in none of the lesions treated with dual probes. Mean margins were 0.9 cm: 1.2 cm for the single probe and dual probe techniques, respectively. Liver surrounding control agar lesions demonstrated a thin rim of necrosis, approximately 0.5 mm wide. CONCLUSIONS: We conclude that minilaparotomy is an effective, safe, and simple method for performing hepatic cryosurgery in this animal model. This minimally invasive technique may benefit a subset of patients with lesions in accessible locations. Lesions in posterior locations may not be as amenable to this technique due to deterioration of ultrasound image quality in the far field.

Expression of bcl-2, p53, and p21 in benign and malignant prostatic tissue before and after radiation therapy.

Abnormalities in genes of the apoptotic pathway might contribute to survival in prostatic cancer (PCa) cells after radiation therapy (RT). We investigated the immunohistochemical expression of the products of the p53, p21WAF1, and bcl-2 genes in pre-RT and post-RT biopsy specimens from 38 patients with locally advanced PCa. All of the 38 patients underwent a uniform protocol of RT with or without neoadjuvant hormonal therapy. Immunohistochemical staining for expression of the products of the p53, p21WAF1, and bcl-2 genes was performed on material from pre-RT and post-RT specimens. Sufficient tissue for analysis was available from 25 of the pre-RT and 38 of the post-RT biopsy specimens. In benign prostatic epithelium, RT resulted in expression of p53 (2 [8%] of 25 pre-RT specimens vs. 15 [71%] of 21 post-RT specimens; P < .001) and increased expression of bcl-2 (1 [5%] of 18 pre-RT vs. 18 [86%] of 21 post-RT; P < .001). There was no change in the expression of p21WAF1 (1 [4.5%] of 22 pre-RT vs. 4 [17%] of 23 post-RT; P = NS). Post-RT specimens were positive for PCa in 24 (63%) of 38 cases. In the PCa tissue, p53 expression was seen in 10 (42%) of 24 pre-RT and 12 (63%) of 19 post-RT samples (P = NS). A significant upregulation of p53 was seen in the subgroup of patients who did not receive neoadjuvant hormonal therapy (9 [82%] of 11 vs. 3 [38%] of 8; P = .05). No significant change in p21WAF1 (5 [21%] of 24 vs. 5 [33%] of 15; P = NS), or bcl-2 (4 [18%] of 22 vs. 3 [21%] of 14; P = NS) expression was detected. There was no significant correlation between immunohistochemical expression of apoptosis-related markers and treatment failure. We concluded that RT induced upregulation of the bcl-2 and p53 gene products in benign prostatic tissue and that this likely reflected a protective mechanism in genetically unaltered epithelium. Increased p53 expression in PCa was only seen in patients without neoadjuvant hormonal treatment, indicating that the cancer cells with abnormal p53 were at least partially protected from RT-induced cell death.

Correlation of color Doppler flow in the prostate with tissue microvascularity.

BACKGROUND: The pathophysiology of increased color Doppler (CD) flow has not previously been addressed in histologic evaluations of microvascular parameters. In this study, the authors attempted to define the differences between benign and malignant biopsy cores found in regions of the prostate with normal and high CD flow. METHODS: Forty patients were retrospectively chosen for CD histologic comparison, each of whom had a core from a sextant biopsy with the following characteristics: malignant tissue with distinct increased CD flow (n=11), malignant tissue with normal CD flow (n=10), benign tissue with distinctly increased CD flow (n=9), or benign tissue with normal CD flow (n=10). All biopsy cores were stained with factor VIII-related antigen to identify microvasculature and to determine the number of microvessels per square millimeter (mm2) in an average cross-sectional area of microvessels, the percentage of tissue occupied by microvasculature, and the Gleason score. RESULTS: In biopsies of benign tissue, high CD flow was associated with greater numbers (P < 0.025) of vessels of similar size than in normal flow benign biopsies. Biopsies of malignant tissue contained significantly greater numbers (P < 0.01) of much smaller vessels (P < 0.0005) than biopsies of benign tissue. In biopsies of malignant tissue, no significant differences in microvasculature parameters were noted between high and normal CD flow, yet biopsies with high CD flow had average Gleason score of 6.7 compared with only 5.9 for biopsies with normal CD flow (P < 0.025). CONCLUSIONS: Increased CD flow in biopsies of benign tissue was correlated with a greater number of vessels/mm2, yet all biopsies of malignant tissue had more vessels/mm2 than those of benign tissue. Increased CD flow in biopsies of malignant tissue cannot be explained by standard microvasculature analysis but significantly guides biopsies to regions with a greater Gleason score.

Minimally invasive alternatives to traditional operative hepatic cryoablation: works in progress.

Primary and secondary malignant disease of the liver remains a major health problem in the United States and abroad. It is estimated that over 130,000 new cases and 55,000 deaths will result from colorectal carcinoma in 1997. In this same year, 13,600 new cases and 12,400 deaths are also expected to result from primary hepatic tumors. Worldwide, hepatocellular carcinoma results in approximately 250,000 deaths yearly.

Observations on the early detection of prostate cancer from the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society National Prostate Cancer Detection Project (ACS-NPCDP) was established in 1987. The experience of the ACS-NPCDP demonstrates the yield and impact of periodic examinations for the early detection of prostate cancer. METHODS: A cohort of 2999 well men ages 55-70 years was tested annually at 10 clinical centers by prostate specific antigen (PSA), transrectal ultrasound (TRUS), and digital rectal examination (DRE). Biopsies were performed on men with suspicious findings. Pathologic findings were reviewed. The initial study outcomes were the detection yield of multimodality testing and the comparative sensitivity and specificity of the different tests employed. Longer term outcomes included patient quality of life and survival. RESULTS: The cancer detection rate declined significantly across the years of intervention. DRE had lower sensitivity than TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that of DRE. Fewer than 9% of the cancers detected in this study were clinically advanced at the time of diagnosis. Ninety-four percent of patients in whom cancer was detected are alive after an average follow-up of 54 months. In one case, death occurred after surgery. Two deaths were attributed to prostate cancer, and eleven other deaths were unrelated to prostate cancer or its treatment. CONCLUSIONS: Results of the ACS-NPCDP indicate that a combined-modality approach to prostate cancer detection yields high levels of early detection with infrequent adverse outcomes. Continued follow-up is required to evaluate long term morbidity and mortality.

Future benefits and cost-effectiveness of prostate carcinoma screening. American Cancer Society.

BACKGROUND: Estimates of cost-effectiveness for prostate carcinoma screening require a review of current data, modeling efforts, and perspectives on societal impact and costs. METHODS: Recent data from the cancer registry of the Michigan Department of Community Health was assessed for incidence trends in relation to age groups and racial differences. Differences in tumor biology between African-American men (AAM) and white men were assessed from a large clinical biopsy series. A review of the literature addressing Markoff modeling to obtain estimates of treatment, screening efficacy, and costs were evaluated. RESULTS: The decline in the incidence of prostate carcinoma since 1992 primarily affected men age > 70 years whereas younger men (age 45-70 years) maintained a 100% greater incidence of localized disease than in 1989, when prostate specific antigen screening became more common. The rate of distant disease has decreased by 60% for both age groups. In the current biopsy series, AAM have distinctly more cores involved with carcinoma and have a higher number of carcinoma cores involved with a Gleason score > or = 7 in men age < or = 70 years with a PSA level < or = 10 ng/ mL (P < 0.05). Markoff models reviewed in the literature demonstrated significant sensitivity to progression, complication, and comorbidity rates. Recent models suggested significant increases in quality-adjusted life expectancy for men choosing radical prostatectomy over watchful waiting if they were age < 70 years and had no severe comorbidities. Original cost estimates from benefit-cost analysis showed similar results of cost per carcinoma and cost per quality-adjusted life-year extension as later cost-effectiveness models. CONCLUSIONS: Current diagnostic trends toward the persistent increased detection of localized prostate carcinoma in younger men, combined with a marked reduction in distant stage disease, suggest significant potential mortality reductions. These trends may have greater implications for AAM, but further research is needed to produce models of mortality reduction from emerging data.

Outcome of African American men screened for prostate cancer: the Detroit Education and Early Detection Study.

PURPOSE: Will early detection impact on stage of disease and recurrence of prostate cancer in a high risk population? We initiated a community based study to educate and recruit African American men for early diagnosis of prostate cancer, that is the Detroit Education and Early Detection (DEED) study. Our objective was to evaluate our recruitment process for this target population, examine the percentage of organ confined prostate cancer in men undergoing radical prostatectomy and measure recurrence biochemically. MATERIALS AND METHODS: A community based study from February 1993 to February 1995 through the African American churches in metropolitan Detroit was initiated. We compared the early detection group treated with radical prostatectomy to the population presenting to our urological clinic during the same period. We tested and followed 1,105 African American men using the prostate specific antigen blood test. RESULTS: Pathologically organ confined prostate cancer was diagnosed in 11 of 17 men (65%) who underwent radical prostatectomy in the DEED project. Within the clinic population 35% of the African American men were diagnosed with pathologically organ confined prostate cancer. The difference between the 2 populations was statistically significant (p = 0.033). Disease recurred in 1 of 15 (7%) and 39 of 157 (25%) men in the DEED and clinic populations, respectively (p = 0.97). CONCLUSIONS: We demonstrated our ability to recruit African American men into a prostate cancer early detection program. We diagnosed early but clinically significant prostate cancers among African American men with characteristics similar to prostate cancers diagnosed in other early detection studies in which the overwhelming majority of men were white.

Conformal mixed neutron and photon irradiation in localized and locally advanced prostate cancer: preliminary estimates of the therapeutic ratio.

PURPOSE: To determine the incidence of chronic toxicity and the probability of biochemical and histologic complete response among patients with nonmetastatic prostate cancer, treated with three dimensional (3D) conformal mixed neutron and photon irradiation. METHODS AND MATERIALS: Between November 1991 and December 1994, 151 patients with prostate cancer were entered in three prospective dose-finding studies of conformal mixed neutron and photon irradiation. Patients with low stage, low to intermediate grade prostate cancer (T1-2NXM0, Gleason Score < or = 7) received 38 Photon Gy (PhGy) plus 9 (51 patients) or 10 (53 patients) Neutron Gy (NGy) to the prostate and seminal vesicles. Forty-seven patients with locally advanced prostate cancer (T3-4 N0-1 M0 and/or Gleason Score > or = 8) received 15 NGy + 18 PhGy to the prostate and seminal vesicles and 9 NGy + 18 PhGy to the pelvic lymph nodes. RESULTS: The median follow-up was 16 months (range: 3-30 months). There was no Grade 3-5 GI or GU toxicity recorded. At 20 months, the actuarial rates of Grade 2 GI morbidity were 6 and 29% for the 9-10 and 15 NGy protocols, respectively (p = 0.07). At 20 months, the incidences of Grade 2 GU morbidity were 4 and 16%, respectively (p = 0.08). Stiffness in flexing or abducting the hips was seen in 20 and 42% of patients receiving 9-10 and 15 NGy, respectively (p = 0.01). Potency was maintained in 65% of all patients. Among patients with an initial PSA < or = 10, 100% had a 12-month PSA < 2 and 78% < 1 ng/ml. Negative postradiation biopsies were seen in 30% of patients 6 months, 79% at 12 months, and 84% of patients at 18 months. CONCLUSION: The use of conformal mixed neutron and photon irradiation has been well tolerated with no severe bladder or rectal complications observed. However, because of the enhanced toxicity seen with 15 NGy, the current maximum dose levels of neutron irradiation have been limited to 11 NGy.

The results of a five-year early prostate cancer detection intervention. Investigators of the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: The American Cancer Society-National Prostate Cancer Detection Project (ACS-NPCDP) is a multidisciplinary evaluation of early prostate cancer detection interventions. This report summarizes the experience of the investigators to date and describes the overall and relative performance of the different detection modalities studied in this project. METHODS: Two thousand nine hundred ninety-nine men aged 55 to 70 years at entry who were not already under evaluation for prostate cancer were recruited to participate in up to 5 annual examinations by prostate specific antigen (PSA), digital rectal examination (DRE), and transrectal ultrasound (TRUS). In the course of 5 years of intervention, ACS-NPCDP investigators have completed 9937 examinations, recommended 1215 biopsies, and detected 203 cancers. RESULTS: Loss to cohort follow-up was greatest in the first year. Overall, TRUS led to twice the number of recommendations for biopsy compared with DRE (8.9% versus 4.4%). Elevated PSA was observed in 13.0% of 9535 measurements performed. The overall cancer detection rate declined significantly during the five years of intervention. Detection was significantly associated with age and symptom status at entry. DRE had lower sensitivity compared with TRUS or PSA, particularly in later years of follow-up. The specificity of TRUS was lower than that for DRE. PSA was elevated in 69.2% of examinations that led to cancer detection, compared with only 10.9% when cancer was not found. PSA level, PSA density, and PSA change were all related to the presence of cancer. Less than 6% of the cancers detected in this study were clinically advanced at the time of diagnosis. CONCLUSIONS: These data quantify the yield of early cancer detection that may be expected when PSA, DRE, and TRUS are used in populations comparable to the men participating in the ACS-NPCDP. Continued follow-up and further research is needed to assess whether men receiving early prostate cancer interventions benefit as a result.

Cost-effective prostate cancer detection. Reduction of low-yield biopsies. Investigators of the American Cancer Society National Prostate Cancer Detection Project.

BACKGROUND: In hopes of limiting low-yield prostate biopsies, results of digital rectal examination (DRE), transrectal ultrasound (TRUS), prostate specific antigen (PSA) and age-related PSA values, gland-volume-adjusted PSA levels, and longitudinal PSA changes were analyzed to identify their cost-effectiveness as prognostic indicators in screening, biopsy, and follow-up of patients with prostate cancer. METHODS: Twenty-nine hundred men with complete data sets from an initial cohort of 2999 men with an annual follow-up for up to 5 years were examined. Intrapatient PSA and gland-volume variability, optimal PSA operating points (o.p.), and test performance scores were determined for each parameter. Decision analysis was then applied retrospectively to each parameter to determine the cancer detection yield, biopsy requirements, and costs for commonly used detection strategies. RESULTS: For the initial screening decision, the optimal PSA o.p. was 3.0 ng/ml but increased to 5.0 ng/ml in combination with DRE, whereas age-related PSA performed no better than did PSA. The mean intrapatient variability in TRUS gland volume (+5.5 cc) relative to mean volume (34 cc) was 16%, which was less than the 28% (0.64/2.3 ng/ml) relative variability for PSA. For biopsy decisions, using PSA density (PSAD) with a level of 0.12 ng/ml/cc there was no significant difference in accuracy compared with the systematic biopsy of all patients with elevated PSA or age-related PSA levels. Rather than perform systematic biopsy on all patients with PSA levels greater than 4 ng/ml, decision analysis showed that a 16-55% reduction in biopsies could be achieved with a respective cancer loss of 4-25% by limiting biopsy to patients with an increased PSAD level and/or abnormal results of DRE. Using age-related PSA criteria in combination with DRE reduced biopsies by 12% but resulted in minimal cost reductions. The greatest biopsy reduction relative to cancer yield and lowest cost per cancer detected occurred with PSAD-driven biopsy strategies. During follow-up, longitudinal changes in absolute PSA and PSAD levels were significantly better (P < 0.05) than the percentage change in PSA levels per year. CONCLUSIONS: Cost-effective prostate cancer detection with PSA as a parameter is better achieved if screening and biopsy decisions are not linked intimately. A tailored-biopsy approach for patients with disproportionately elevated PSA levels of suspicious DRE results in the greatest biopsy reduction by selecting lower risk groups for more conservative follow-up.

Characteristics of prostate cancer detected in the American Cancer Society-National Prostate Cancer Detection Project.

The American Cancer Society-National Prostate Cancer Detection Project is a prospective, comparative study of a cohort of 2,999 men 55 to 70 years old not suspected on entry of having prostate cancer. A total of 164 prostate cancers is available from this project for analysis. A small proportion of tumors detected were advanced in terms of the clinical stage at diagnosis. Cancer detected by digital rectal examination tended to be more advanced than that found on the basis of only transrectal ultrasound or prostate specific antigen (PSA). A large proportion of patients received curative therapy involving radical prostatectomy in 67.1% and radiotherapy in 18.3%. Of 103 men presumed to have organ confined disease and treated by prostatectomy 64 (37.9%) actually had locally extensive cancer pathologically. PSA level and PSA density were associated with the detection of organ confined cancer but several advanced tumors had PSA levels in the normal range. Age referenced PSA, compared to conventional standards, demonstrated lower sensitivity to cancer with little improvement in specificity. The disease resulting from this multimodality detection effort represented a spectrum of pathological conditions. Further followup and evaluation are needed to determine whether these benefits are reflected in long-term mortality and survival experience.