Usefulness of prostate-specific antigen velocity in screening for prostate cancer

BACKGROUND: The cut-off value of prostate-specific antigen velocity (PSAV) was investigated in relation to the initial prostate-specific antigen (PSA) value in subjects with initial values of 1.0-4.0 ng/mL, and the usefulness and limitations of PSAV as a screening test for prostate cancer were examined. METHODS: In this study, 4883 men who underwent mass screening for prostate cancer two or more times between 1987 and 1998 and had initial PSA levels of 1.0-4.0 ng/mL were investigated. The subjects ranged in age from 42 to 96 years (mean: 68.0 +/- 6.6 years). The cut-off value of PSAV was set at 0.1-1.5 ng/mL per year, and the sensitivity, specificity, efficiency and positive predictive value (PPV) of PSAV for detecting prostate cancer were determined according to the initial PSA value. A similar examination of the average PSAV was carried out in 2888 subjects with three or more visits for mass screening for prostate cancer. RESULTS: The diagnostic efficiency of PSAV was optimal with cut-off values of 0.3 and 0.75 ng/mL per year in those subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 1.8% in subjects with initial PSA levels of 1.0-1.9 ng/mL. When the cutoff value of PSAV was set at 1.2 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV increased to 7.3% and the sensitivity was 40%. The diagnostic efficiency of the average PSAV was optimal at the cut-off values of 0.2 and 0.4 ng/mL per year in subjects with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively, but the PPV was low at 2.2% in the subjects with initial PSA values of 1.0-1.9 ng/mL. When the cut-off value of PSAV was set at 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 ng/mL, the PPV was 9.8% and the sensitivity was 46%. CONCLUSION: It is possible to improve the diagnostic accuracy of prostate cancer screening using the cut-off value of PSAV and average PSAV in subjects with initial PSA levels of 1.0-4.0 ng/mL. The cut-off values of PSAV should be set at 1.2 and 0.75 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively. The cut-off values of the average PSAV should be set at 0.75 and 0.4 ng/mL per year in individuals with initial PSA levels of 1.0-1.9 and 2.0-4.0 ng/mL, respectively.     

The utility of prostate-specific antigen velocity thresholds in clinical practice: a population-based analysis

OBJECTIVE

To investigate the ability of prostate‐specific antigen velocity (PSAV) to predict prostate cancer, and assess the test characteristics of several PSAV thresholds for identifying prostate cancer and high‐grade cancers.

PATIENTS AND METHODS

From a population‐based database of PSA results, men with an initial PSA level of <10.0 ng/mL, taken between I January 1994 and 31 December 2003, were identified. Those with three or more PSA tests before diagnosis, taken over ≥18 months, were included. Men were followed for a diagnosis of prostate cancer or histologically confirmed benign disease until 31 December 2003.

RESULTS

In all, 24 709 men were included, with 716 (2.9%) diagnosed with prostate cancer and 1488 (6.0%) with benign histology. The mean (10.38 vs 0.43 ng/mL/year) and median (1.47 vs 0.03 ng/mL/year) PSAV were considerably higher in men with prostate cancer than in those with no cancer (P < 0.001). There was no PSAV threshold that could reliably identify prostate cancer or high‐grade cancers without requiring many men to proceed to prostate biopsy.

CONCLUSION

In this population, PSAV had additional value over one PSA value in identifying men with prostate cancer. Many men with prostate cancer might have a ‘normal’ (<0.75 ng/mL/year) PSAV. As with total PSA level, there was no PSAV threshold that could reliably predict prostate cancer, but rather a continuum of risk of cancer associated with PSAV level.     

Prostate-specific antigen velocity (PSAV) risk count improves the specificity of screening for clinically significant prostate cancer

Study Type – Prognosis (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? PSA screening reduces prostate cancer mortality but also may lead to unnecessary biopsies and overdiagnosis of insignificant tumours. PSA velocity (PSAV) risk count (number of serial PSAV exceeding 0.4 ng/ml/year) significantly improves the performance characteristics of screening for overall prostate cancer and high‐grade disease on biopsy. Risk count may be useful to reduce unnecessary biopsies and prostate cancer overdiagnosis compared to PSA alone.

OBJECTIVE

• ? To determine whether the prostate‐specific antigen velocity (PSAV) risk count (i.e. the number of times PSAV exceeds a specific threshold) could increase the specificity of screening for prostate cancer and potentially life‐threatening tumours.

PATIENTS AND METHODS

• ? From 1989 to 2001, we calculated two serial PSAV measurements in 18 214 prostate cancer screening‐study participants, of whom 1125 (6.2%) were diagnosed with prostate cancer.
• ? The PSAV risk count was determined as the number of PSAV measurements of >0.4 ng/mL/year (0, 1, or 2).
• ? We used receiver operating characteristic (ROC) and reclassification analyses to examine the ability of PSAV risk count to predict screen‐detected and high‐grade prostate cancer.

RESULTS

• ? The PSAV was >0.4 ng/mL/year twice (risk count 2) in 40% of prostate cancer cases compared with only 4% of those with no cancer (P < 0.001).
• ? After adjusting for age and PSA level, a PSAV risk count of 2 was associated with an 8.2‐fold increased risk of prostate cancer (95% confidence interval 7.0–9.6, P < 0.001) and 5.4‐fold increased risk of Gleason score 8–10 prostate cancer on biopsy.
• ? Compared with a model with age and PSA level, the addition of the PSAV risk count significantly improved discrimination (area under the ROC curve 0.625 vs 0.725, P= 0.031) and reclassified individuals for the risk of high‐grade prostate cancer (net reclassification, P < 0.001).

CONCLUSIONS

• ? Sustained rises in PSA indicate a significantly greater risk of prostate cancer, particularly high‐grade disease.
• ? Compared with men with a risk count of ≤1, those with two PSAV measurements of >0.4 ng/mL/year (risk count 2) had an 8‐fold increased risk of prostate cancer and 5.4‐fold increased risk of Gleason 8–10 disease on biopsy, adjusting for age and PSA level.
• ? Compared to PSA alone, PSAV risk count may be useful in reducing unnecessary biopsies and the diagnosis of low‐risk prostate cancer.

     

PSA velocity for assessing prostate cancer risk in men with PSA levels between 2.0 and 4.0 ng/ml

Objectives. To evaluate the use of prostate-specific antigen (PSA) velocity (PSAV) in assessing prostate cancer risk among men with PSA levels less than 4.0 ng/mL.Methods. The relative risk of, and cumulative probability of freedom from, prostate cancer by PSAV was evaluated in 89 male participants (21 with cancer and 68 controls) of a longitudinal aging study—the Baltimore Longitudinal Study of Aging (National Institute on Aging)—who had serial PSA levels between 2.0 and 4.0 ng/mL for at least 18 months. The relative risk was estimated from a Cox proportional hazards regression model, and the disease-free probability was determined by Kaplan-Meier survival analysis. The sensitivity and specificity of PSAV were calculated as a measure of test validity.Results. The sensitivity and specificity of a PSAV of 0.1 ng/mL per year was 81% and 50%, respectively. The relative risk of prostate cancer was 6.53 (range 1.90 to 22.51) when the PSAV was 0.1 ng/mL per year or more compared with a PSAV of less than 0.1 ng/mL per year (P = 0.0029). At 10 years, the cumulative probability of freedom from prostate cancer was 97.1% (range 91.4% to 100%) and 35.2% (range 14.0% to 56.4%) when the PSAV was less than and greater than 0.1 ng/mL per year, respectively. Survival curves began to differ at less than 5 years after the baseline PSAV determination.Conclusions. The association between PSAV and the subsequent risk of prostate cancer suggests that the PSAV may be useful in the risk assessment of men with lower PSA levels.     

Methods of calculating prostate-specific antigen velocity

OBJECTIVES: Numerous methods of calculating PSA velocity (PSAV) are used and have the potential to produce differing PSAV results from the same PSA data. We calculated PSAV using three common methods and compared differences between the methods and their predictive value for prostate cancer diagnosis. METHODS: From a population-based database of PSA results, men with initial PSA<10.0 ng/ml and a subsequent diagnosis of prostate cancer or benign histology were identified. Those with > or =3 PSA tests before diagnosis carried out over a minimum of 18 mo were included. PSAV was calculated by using three methods: The differences between the methods and test characteristics of each method were compared. RESULTS: Of the 2204 men included, 716 (32.5%) were diagnosed with prostate cancer and 1488 (67.5%) benign histology. PSAV differed markedly in each method of calculation. The LR and FL methods had similar predictive values, which were higher than the AE method. There was strong agreement for cancer diagnosis between LR and FL (kappa=0.85), with weaker agreement between LR/AE and FL/AE (kappa=0.69 and 0.66, respectively). CONCLUSIONS: Methods used to calculate PSAV using the same PSA data can produce markedly different results. Linear regression should be the method of choice for calculating PSAV. Using first and last PSA values only may be adequate for everyday clinical use, as long as measurements are separated by a sufficiently long time period.     

Is the utility of prostate‐specific antigen velocity for prostate cancer detection affected by age?

OBJECTIVE

To determine whether prostate‐specific antigen velocity (PSAV) is useful for prostate cancer detection in men from different age groups, and whether the same PSAV thresholds can reasonably be applied to all men aged ≥40 years.

PATIENTS AND METHODS

From a large prostate cancer screening study, 13 615 men had data on age and a calculable PSAV. We used statistical analysis to examine the ability of PSAV to predict prostate cancer risk in each age decade.

RESULTS

For men of all ages, the median PSAV was 0.6–0.7 ng/mL/year in men with prostate cancer, and 0–0.1 ng/mL/year in men with no prostate cancer (P < 0.005 for all). On receiver operating characteristic (ROC) analysis, the area under the curve was 0.800, 0.697, 0.693, and 0.668 for predicting prostate cancer risk using PSAV for men aged 40–49, 50–59, 60–69 and ≥70 years, respectively. In the multivariate model controlling for race, family history, and the total PSA level, both PSA and PSAV were significant independent predictors of prostate cancer risk in men of all ages.

CONCLUSIONS

The PSAV is significantly higher in men of all ages with prostate cancer compared with men with no prostate cancer; although on ROC analysis it performed the best in young men. Interestingly, the median PSAV in men with prostate cancer was <0.75 ng/mL/year regardless of age, suggesting that this threshold may be too high. Overall, this data confirms that PSAV is a useful tool for prostate cancer detection for men aged ≥40 years.     

Prostate-specific antigen (PSA) and PSA velocity for prostate cancer detection in men aged <50 years

OBJECTIVE: To identify threshold values of prostate-specific antigen (PSA) levels and PSA velocity (PSAV) to optimize the assessment of the risk of prostate cancer in young men, as prostate cancer is detected increasingly in men aged <50 years. PATIENTS AND METHODS: Data for a group of 12 078 men, including 1622 with prostate cancer, were retrieved from the Duke Prostate Center Database. Based on the latest date for a PSA assay, these men were divided into two age groups of <50 and >/= 50 years, with 904 and 11 174 men in each group, respectively. Receiver operating characteristic curves (ROC) of PSA and PSAV were calculated and the cancer risk was assessed. RESULTS: The prevalence of prostate cancer was 4.4% (40 men) for men aged <50 years and 14.2% (1582 men) for men aged >/= 50 years. For the group with cancer the median PSA in men aged <50 years was significantly lower than that in men aged >/= 50 (1.3 vs 6.3 ng/mL, P < 0.001). ROC curves of PSA and PSAV showed a breakpoint at a PSA level of 2.3 ng/mL and a PSAV of 0.60 ng/mL/year for men aged <50 years. Both the sensitivity and specificity in the younger group at a PSA level of 2.5 ng/mL were higher than in the older group. CONCLUSIONS: In men aged <50 years the operating characteristics of PSA are more sensitive and specific than in older men. Diagnostic PSA levels in men aged <50 years are significantly lower than suggested by guidelines. Using a 2.0-2.5 ng/mL PSA level threshold for biopsy in men aged <50 years and a PSAV threshold lower than the traditional 0.75 ng/mL/year is reasonable in contemporary practice. Further studies are warranted to validate these thresholds.     

Does PSA velocity predict prostate cancer in pre-screened populations?

PSA-driven screening has been applied to a large part of the male population in many countries. An elevated PSA in secondary screens may indicate benign enlargement of the prostate rather than prostate cancer. In such cases the yearly rate of increase of PSA (PSA velocity [PSAV]) may improve the test characteristics of PSA. MATERIALS AND METHODS: Data from the European Randomized Study of Screening for Prostate Cancer Rotterdam are used to study the issue. Relative sensitivity, relative specificity, and positive predictive value (PPV) are calculated. Logistic regression analysis is used to compare odds ratios for positive biopsies. The relationship between PSAV and parameters of tumour aggressiveness is investigated. RESULTS: Five hundred eighty-eight consecutive participants were identified who presented at their first screening with PSA values <4.0 and who progressed to PSA values >4.0 ng/ml four years later. None were biopsied in round one, all were biopsied in round two. Relative sensitivity and specificity depend strongly on PSAV cut-offs of 0.25-1.0 ng/ml/yr. The use of PSAV cut-offs does not improve the PPV of the PSA cut-off of 4.0 ng/ml, nor do any of the PSAV cut-offs improve the odds ratio for identifying prostate cancer with respect to the cut-off value of 4.0 ng/ml. The rate of aggressive cancers seems to increase with increasing PSAV. CONCLUSIONS: PSAV does not improve the detection characteristics of a PSA cut-off of 4.0 ng/ml in secondary screening after four years.     

Community‐based prostate cancer screening in Japan: Predicting factors for positive repeat biopsy

Objectives: To assess possible predictors in determining criteria for repeat biopsy in a prostate cancer screening population. Methods: A total of 50 207 men over 55 years‐of‐age have participated in a prostate cancer screening program in Otokuni, Kyoto, Japan for 12 years. Transperineal systematic biopsy was carried out in case of positive digital rectal examination (DRE) or positive transrectal ultrasonography (TRUS) or a prostate‐specific antigen (PSA) value greater than 10.0 ng/mL. For those with a PSA level from 4.1 to 10.0 ng/mL, and negative DRE and TRUS findings, biopsy was indicated only when PSA density (PSAD) was greater than 0.15. The same indication was applied for the repeat biopsy. Results: A repeat biopsy after an interval of more than 2 years was carried out in 140 patients and was positive in 50 (36%) patients. The PSA value at the diagnosis of cancer declined from the initial value in six (12%) patients. On multivariate logistic regression analysis, PSA velocity (PSAV) as well as PSAD and DRE findings at latest screening were independent predictors for positive repeat‐biopsy outcome. The odds ratio (95% confidence intervals) of PSAV >0.48, latest PSAD >0.33 and positive latest DRE were 4.17 (1.05–18.5), 4.15 (1.31–14.0), and 3.62 (1.06–13.2), respectively. A combination of three variables defined as positive if any of these were positive, reduced 31% of unnecessary biopsies while missing 8% of low volume, low grade cancers. Conclusions: A combination of latest PSAD, PSAV and positive DRE at latest screening might help to reduce unnecessary repeat biopsies in high‐risk patients with an initial negative biopsy.     

Diagnostic significance of digital rectal examination and transrectal ultrasonography in men with prostate-specific antigen levels of 4 ng/mL or less

Objectives. To investigate the usefulness of digital rectal examination (DRE) and transrectal ultrasonography (TRUS) for prostate cancer diagnosis and to propose a diagnostic algorithm for individual-based cancer screening in subjects with prostate-specific antigen (PSA) levels of 4.0 ng/mL or less.Methods. Between January 1992 and March 2000, 129 subjects with PSA levels of 4.0 or less and abnormal findings on DRE or TRUS underwent prostate biopsy. The subjects were divided into four groups according to the PSA range: 0 to 0.9 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL. The reliability of the DRE and TRUS and the clinicopathologic features of prostate cancer were investigated among these four groups.Results. Of the 129 subjects, 17 (13.2%) patients with prostate cancer were diagnosed. The detection rate was 2.2% (1 of 45), 0% (0 of 27), 20.6% (7 of 34), and 39.1% (9 of 23) in subjects with PSA levels of less than 1.0 ng/mL, 1.0 to 1.9 ng/mL, 2.0 to 2.9 ng/mL, and 3.0 to 4.0 ng/mL, respectively. The proportion of patients with Stage II, III, and IV was 58.8%, 41.2%, and 0%, respectively. The percentage with Gleason scores of 8 to 10 was 17.6%. The detection rate of abnormal findings on DRE and TRUS was 14.4% (13 of 90) and 9.5% (7 of 74), respectively. Adding TRUS to DRE in the screening program of subjects with PSA levels of 2.0 to 4.0 ng/mL, increased the detection rate of prostate cancer to 30.8% (4 of 13).Conclusions. Routine prostate biopsy should not be undertaken except for highly suspicious DRE findings in subjects with PSA levels less than 2.0 ng/mL. The additional use of TRUS in subjects with PSA levels of 2.0 to 4.0 ng/mL would improve the sensitivity of prostate cancer detection. The diagnostic algorithm proposed in the present study is useful as a screening method for prostate cancer in subjects with PSA levels of 4.0 ng/mL or less.     

The role of prostate-specific antigen velocity in prostate cancer early detection

Prostate-specific antigen velocity (PSAV) is the rate of change in prostate-specific antigen (PSA) values with repeated measurement over time. Accurate use of PSAV for prostate cancer early detection requires the use of two or more PSA levels collected over approximately 1.5 to 2 years. When these specimen collection criteria are met, more than 95% of men without prostate cancer will have a PSAV less than 0.75 ng/mL/y, whereas approximately 70% of men with prostate cancer will have a PSAV above this threshold. PSAV is thus more specific than routine PSA testing for the presence of prostate cancer, because few men (< 5%) without prostate cancer have a PSAV sufficient to trigger prostate biopsy. The use of PSAV in the increasing number of men with lengthy PSA histories obtained in systematic efforts at prostate cancer early detection may aid in diagnosing prostate cancer and spare some men unnecessary prostate biopsy. This review briefly summarizes the theoretic basis and clinical utility of PSAV in prostate cancer early detection.     

Longitudinal PSA changes in men with and without prostate cancer: assessment of prostate cancer risk

BACKGROUND: To determine longitudinal PSA changes over a period of 10 years in patients with and without prostate cancer. METHODS: Serial PSA measurements performed over 10 years were evaluated in 353 men who eventually developed prostate cancer and in 2.462 participants of a screening program without prostatic malignancy. RESULTS: In men with cancer, mean tPSA increased from 2.28 ng/ml at 10 years before diagnosis to 6.37 ng/ml at the time of postive biopsy (PSA velocity: 0.409 ng/ml/year). PSA velocity was significantly associated with Gleason scores and pathologic stage. In the benign group (n=2.462), mean tPSA increased from 1.18 to 1.49 ng/ml over a period of 10 years (PSA velocity of 0.03 ng/ml/year). Of the subjects with tPSA levels of 2 ng/ml or less, 2 years prior to cancer diagnosis, 11.4% had tPSA values of more than 4 ng/ml at the time of biopsy. Of the 972 men with tPSA below 1 ng/ml 2 years before the most recent measurement was obtained, 966 (99.4%) had no evidence of prostate cancer 2 years later, while six were found to have malignancies (0.6%). CONCLUSIONS: Longitudinal PSA changes in men with and without prostate cancer are significantly different. Annual testing may not be required in men with baseline tPSA levels of 1 ng/ml or below, whereas in patients with levels higher than 1 ng/ml, it seems to be indicated because of the significant percentage of men presenting with tPSA levels of more than 4 ng/ml two years later.     

Routine bone scans in patients with prostate cancer related to serum prostate-specific antigen and alkaline phosphatase

OBJECTIVE: To evaluate the need for a bone scan as a routine staging procedure in patients with newly diagnosed prostate cancer in relation to serum prostate-specific antigen (PSA) and alkaline phosphatase (ALP) levels, and thus determine whether a reduction of the use of this staging method is possible in patients with a low probability of osseous metastasis. PATIENTS AND METHODS: The results of bone scans were related retrospectively to levels of serum PSA and ALP in 363 patients with prostate cancer newly diagnosed between 1989 and 1997. RESULTS: Of 363 consecutive patients, 111 had a positive bone scan. In 19 of 144 (13%, "missed diagnosis") patients with a PSA level of < 20 ng/mL the bone scan was positive. In 125 patients (49%, "false-positives") with a PSA level of > 20 ng/mL the bone scan was negative. A threshold level of 100 U/L for ALP gave a better balance for the number of "false-positives" and "missed diagnosis". ALP values correlated better with an abnormal bone scan than did PSA levels; ALP levels of > 90 U/L indicated a 60% chance for the presence of bone metastases. CONCLUSION: Patients with newly diagnosed and untreated prostate cancer should undergo bone scintigraphy if there is bone pain or if ALP levels are > 90 U/L. Recent reports discourage the routine use of a bone scan when the serum PSA level is <20 ng/mL. However, the present series suggests there is a greater chance of a positive bone scan in patients with low PSA levels; these findings need further confirmation.     

Early diagnosis of prostate cancer in patients with prostate symptoms by DRE, PSA, TRU and DPSA

Presentation of our experience in the early diagnosis of prostate cancer in patients with signs and symptoms of prostatism. Over a one year period (96-97), 316 patients underwent biopsy based on clearly defined criteria according to the diagnostic algorithm used in our centre: suspicious DRE and/or PSA > or = 10 ng/mL, and in patients with PSA between 4 and 10 ng/mL in the presence of suspicious TRU or when DPSA was > or = 0.15. The ratio of the 136 (43%) prostate cancer diagnosed relative to biopsy +/- was 1:1.32. It is concluded that early diagnosis in a selected population is useful and shows good diagnostic yield. The diagnostic algorithm used is more than acceptable with 43% positive biopsies and a good ratio between biopsy +/-. With a cutoff of 0.15 DPSA is a good method to improve PSA significance in patients in the difficult PSA range of 4 to 10 ng/mL.     

Clinical features of prostate cancer patients younger than 50 years: Report of seven cases

BACKGROUND: The incidence of prostate cancer increases with age and latent cancer is common in older men. But clinical prostate cancer is rare in men aged < 50 years. METHODS: Between 1988 and 2000, we studied seven cases of prostate cancer in men aged under 50 years. The clinicopathological results included: the first sign or symptom; prostate-specific antigen (PSA) at the time of diagnosis; existence of abnormal digital rectal examination (DRE); the differentiation of the cancer and Gleason score; and the outcome of treatment. RESULTS: Six cases were diagnosed as stage D2. One case was diagnosed as stage B2 and the patient underwent radical prostatectomy. None of the cases were detected by mass screening. The PSA at diagnosis was < 10 ng/mL in only one case and that patient underwent radical prostatectomy. Six cases were diagnosed pathologically as poorly differentiated adenocarcinoma. The only patient who survived more than 5 years underwent radical prostatectomy. CONCLUSION: Six of seven cases of prostate cancer were detected at advanced stage. Only one case was thought to be curable and this patient's cancer was detected by chance occult blood test. Because young prostate cancer patients are potential candidates for radical prostatectomy and the sensitivity of PSA might be higher in young men, high-risk groups could be screened by PSA.     

Prostate-specific antigen velocity based risk-adapted discontinuation of prostate cancer screening in elderly men

Study Type – Prognostic (cohort)
Level of Evidence 2b What’s known on the subject? and What does the study add? Currently, the U.S. Preventive Services Task Force (USPSTF) recommends against PSA screening for prostate cancer in men aged ≥75 years as it concluded that “the harm of screening for prostate cancer in men age ≥75 years may outweigh the potential benefits”. Our findings suggest that elderly men with a PSA velocity of ≥0.45 ng/ml/year have higher risk of death from prostate cancer. Continuing PSA testing may be beneficial for these men.

OBJECTIVE

? To evaluate weather prostate‐specific antigen (PSA) velocity could be used to stratify patients at risk of death from prostate cancer (PCa) and be useful in aiding decision making regarding PSA screening in elderly men, as previous studies have shown that PSA velocity can predict PCa risk.

PATIENTS AND METHODS

? The cohort included 3,525 patients aged ≥ 75 years with two or more PSA tests before a diagnosis of PCa. Cox proportional hazard model was used to evaluate which variables at time of last PSA measurement were associated with death from PCa. ? The rates of death from PCa after diagnosis in different PSA velocity groups were calculated. Kaplan‐Meier and log rank test were used to assess the significant difference in death from PCa after diagnosis, stratified by PSA velocity cutoff.

RESULTS

? On multivariate analysis, men with a PSA velocity of PSA velocity ≥0.45 ng/mL/year had a 4.8‐fold higher risk of death from PCa as compared to men with a PSA velocity of <0.45 ng/mL/year (p value = 0.013). After a median 6.5 (up to 16.9) years of follow‐up from diagnosis, 1.4% of the men with a PSA velocity <0.45 ng/mL/year had died of PCa as compared to 8.7% of those with a PSA velocity ≥0.45 ng/mL/year. ? The cumulative rate of death from PCa after diagnosis, stratified by a PSA velocity of 0.45 ng/mL/year, was statistically different (log rank test, P < 0.001).

CONCLUSION

? Men age ≥ 75 years old with a PSA velocity of <0.45 ng/mL/year are unlikely to die of PCa. It may be safe to discontinue PSA screening in these men.     

Value of prostate-specific antigen in the staging of Taiwanese patients with newly diagnosed prostate cancer

Records of 71 patients diagnosed with prostate cancer were reviewed retrospectively regarding clinical stage, prostate-specific antigen (PSA), Gleason score, CT scan of pelvis, bone scan, and pelvic lymph node dissection. Fourteen patients had pelvic lymphadenopathy based on the CT scan. Of these, no patient had a PSA level <4 ng/mL, 1 patient had a PSA level between 4 and 10 ng/mL, and 3 had a PSA level between 10 and 20 ng/mL. Twelve of 13 patients with positive bone scan results had a PSA level >20 ng/mL, and 1 patient had a PSA level between 10 and 20 ng/mL. PSA can be cost-effective in selecting and identifying appropriate staging for patients with newly diagnosed prostate cancer. CT scans are not indicated in men with clinical localized prostate cancer when PSA levels are < or =10 ng/mL. Bone scan is not required for staging asymptomatic men with PSA levels of < or =20 ng/mL. Pelvic lymphadenectomy for localized prostate cancer may not be necessary if PSA levels is < or =20 ng/mL and Gleason score is < or =5.     

The clinical potential of pretreatment serum testosterone level to improve the efficiency of prostate cancer screening

OBJECTIVES: The aim of the present study was to evaluate the clinical value of the pretreatment serum testosterone (T) level as a potential predictor of prostate cancer risk in screening for prostate cancer. MATERIALS AND METHODS: The subjects were 420 patients suspected of having prostate cancer who underwent prostate biopsy, and whose pretreatment T levels were recorded. We checked for association between the presence of prostate cancer and the following clinical factors: pretreatment serum T level, age, pretreatment prostate-specific antigen (PSA) level, digital rectal examination findings, ratio of free to total PSA, prostate volume, and PSA density (PSAD). RESULTS: Overall, there was no significant difference in mean pretreatment T level between patients diagnosed with cancer (3.9+/-2.4 ng/ml) and patients diagnosed with benign prostate disease (BPD; 3.7+/-1.7 ng/ml); diagnosis was based on prostate biopsy. However, among patients with PSA <10 ng/ml, the pretreatment T level was significantly higher in patients diagnosed with prostate cancer (4.2+/-2.6 ng/ml) than in patients diagnosed with BPD (3.6+/-1.4 ng/ml) (p=0.007); a similar trend was observed among patients with PSAD <0.15 ng/ml/cc. Multivariate analysis indicated that pretreatment T level was an independent significant predictor of positive prostate biopsy (p=0.020). Additionally, the serum T level was significantly lower in patients with a Gleason score >or=7 (3.7+/-2.1 ng/ml) versus a score <7 (4.2+/-1.7 ng/ml) (p=0.030). Also, serum T levels were significantly higher in well-differentiated prostate cancer (4.8+/-2.1 ng/ml) versus moderately differentiated (3.8+/-1.3 ng/ml) or poorly differentiated (3.7+/-1.4 ng/ml) (p<0.01). CONCLUSIONS: Among relatively low-risk patients, serum T level was an independent significant predictor of positive prostate biopsy, suggesting that the efficiency of prostate cancer screening can be improved by including measurement of serum T level.     

Diagnostic value of percent free prostate-specific antigen: retrospective analysis of a population-based screening study with emphasis on men with PSA levels less than 3.0 ng/mL

OBJECTIVES: To retrospectively investigate the use of percent free prostate-specific antigen (PSA) compared with total PSA in serum as predictor of prostate cancer in men selected randomly from the general population who underwent biopsy on the basis of abnormal findings on digital rectal examination (DRE) or transrectal ultrasound (TRUS) and/or serum PSA levels greater than 10 ng/mL. METHODS: A single intervention, population-based screening study was undertaken in 1988 and 1989. Of the 2400 men aged 55 to 70 years invited to participate, 1782 men responded and were examined with DRE, TRUS, and PSA testing (Tandem-Hybritech). In 1995, frozen serum samples from 1748 men were analyzed for percent free PSA (Prostatus, Wallac OY). Five-year follow-up data on new cancers in the screened population were obtained from the Swedish Cancer Registry (SCR). RESULTS: Of the 1748 men, 367 underwent TRUS-guided biopsies because of abnormal findings on either DRE or TRUS or serum PSA levels of greater than 10 ng/mL. This resulted in the diagnosis of 64 cases of prostate cancer (3.7%). PSA levels of 3.0 ng/mL or greater were found in 55 (86%) of 64 cancer cases and in 399 (24%) of the 1684 benign cases. Among the 1294 men with PSA less than 3.0 ng/mL, 9 prostate cancers were diagnosed (14% of all prostate cancers). All 9 patients with cancer and with PSA less than 3.0 ng/mL had a percent free PSA of 18% or less. In the group of 1109 patients with PSA less than 3.0 ng/mL and a percent free PSA greater than 18%, 159 biopsies were performed because of abnormal DRE or TRUS. However, no prostate cancer was diagnosed in this category of patients. Five years after the screening intervention, 7 more cases of prostate cancer were clinically diagnosed in the screened population according to the SCR. CONCLUSIONS: The combination of PSA levels less than 3.0 ng/mL and percent free PSA greater than 18% defines a large part of the population at a very low risk of cancer of the prostate both at the time of screening and during the following 5 years. Men in this group may be spared DRE, and longer screening intervals may be considered. However, the risk of having prostate cancer is not negligible in men with PSA less than 3.0 ng/mL and percent free PSA of 18% or less. The results of this study indicate that biopsy should be recommended to men fulfilling these criteria, although these results should be confirmed in larger prospective studies because of the limited number of patients with prostate cancer in the present series.     

Prostate-specific antigen (PSA) kinetics in untreated, localized prostate cancer: PSA velocity vs PSA doubling time

OBJECTIVE

To compare the accuracy of prostate‐specific antigen (PSA) velocity (PSAV) vs PSA doubling time (DT) for predicting the repeat biopsy results in men with localized prostate cancer on active surveillance (AS), as the utility of PSAV vs PSADT in untreated prostate cancer has not been well studied.

PATIENTS AND METHODS

Eligible patients had favourable‐risk localized prostate cancer (T1/2a, PSA level ≤15 ng/mL, Gleason score ≤3 + 4, and percentage positive biopsy cores ≤50%), and consented to AS between 2002 and 2005. Repeat biopsies were taken after 18–24 months, with adverse histology defined as any of: primary Gleason grade ≥4, >50% cores positive, or initial Gleason score 3 + 3 upgraded to ≥3 + 4. Using all PSA values for the 2 years preceding repeat biopsy, the PSAV and PSADT were calculated using linear regression and the log‐slope method (DT = ln2/slope), respectively.

RESULTS

In all, 199 patients were assessable; the median PSAV and PSADT were 0.71 ng/mL/year and 5.29 years, respectively. Fifty‐three patients (27%) had adverse histology on repeat biopsy. On univariate analyses, PSAV (P < 0.001) and PSADT (P = 0.019) were associated with adverse histology. The area under the receiver operating characteristic curve for predicting adverse histology was 0.70 and 0.63 for PSAV and PSADT, respectively. The mean difference was 0.07 (95% confidence interval 0.03–0.12; P < 0.001).

CONCLUSIONS

PSAV is more accurate than PSADT for predicting adverse histology on repeat biopsies. These data suggest that PSAV should be used in preference to PSADT to describe PSA kinetics in untreated, localized prostate cancer.