Prevalence of undiagnosed prostate cancer in men with erectile dysfunction

OBJECTIVE: To explore the prevalence of prostate cancer in men presenting with erectile dysfunction (ED). PATIENTS AND METHODS: In a prospective study, 127 men with ED of at least 6 months duration underwent screening for prostate cancer using prostate specific antigen (PSA) and a digital rectal examination (DRE). Men with a high PSA level (> 4 ng/mL) had sextant biopsies taken under sedoanalgesia. The serum testosterone level was measured in all the men. RESULTS: Twenty-six men were aged < 50 years and all had a normal PSA level; of 101 men aged > 50 years, 20 had an abnormal PSA. The detection rate for prostate cancer using PSA and DRE was 5%, which was not significantly higher than in the general population. All the detected cancers were clinically significant (> T2a, Gleason grade > 4). Two of the five men diagnosed with prostate cancer were Afro-Caribbean. Of the 127 men, 31% had a low serum testosterone level, but there was no association between testosterone and PSA levels. CONCLUSIONS: Prostate cancer is no more common in men with ED than in the normal male population. Therefore, routine screening for prostate cancer in men with ED is not indicated.     

Serum testosterone levels in African-American and white men undergoing prostate biopsy

Objectives. Because androgen levels are known to influence prostate growth, we performed a prospective analysis of serum testosterone levels in all African-American and white men who underwent transrectal ultrasound-guided prostate biopsies to evaluate an abnormal digital rectal examination (DRE) and/or serum prostate-specific antigen (PSA) level greater than 4 ng/mL.Methods. From June 1996 through July 1998, we evaluated 453 men (189 African-American and 264 white men) who underwent prostate needle biopsy because of an abnormal DRE or serum PSA greater than 4 ng/mL, or both. All men had morning serum testosterone levels determined just before undergoing prostate needle biopsy. Serum testosterone levels were compared on the basis of the prostate biopsy result (positive or negative for prostate cancer) and by race.Results. A total of 453 men underwent prostate biopsy and had morning serum testosterone levels available for comparison. Of the 264 white men who underwent biopsy, 88 (33%) were found to have prostate cancer compared with 67 (35%) of 189 African-American men who underwent biopsy. In the white men without cancer, the mean serum testosterone level was 380.19 ng/dL; those with prostate cancer had a mean serum testosterone level of 419.52 ng/dL. The mean serum testosterone level in African-American men without cancer was 424.30 ng/dL; it was 386.55 ng/dL in those with prostate cancer. There was no statistical difference in serum testosterone levels based on biopsy result or race.Conclusions. Although several studies have suggested that African-American men have higher serum testosterone levels than white men, these differences were noted only in men 40 years of age or younger. As was noted in our study, after age 40, African-American and white men have comparable serum testosterone levels. In addition, although prostate growth is androgen dependent, we found no difference in serum testosterone levels in men with and without prostate cancer.     

Prostate‐specific antigen changes and prostate cancer in hypogonadal men treated with testosterone replacement therapy

OBJECTIVES

To retrospectively review hypogonadal men receiving testosterone replacement therapy (TRT), and evaluate the changes in prostate‐specific antigen (PSA) levels over an extended period, and thus evaluate the occurrence of prostate cancer, as a primary concern in treating late‐onset hypogonadism (LOH) is the potential increased risk of prostate cancer; we also recorded the cardiovascular effects of TRT.

PATIENTS AND METHODS

In all, 81 hypogonadal men (mean age 56.8 years) were followed for a mean (range) of 33.8 (6–144) months after starting TRT. All men had a normal baseline PSA level before TRT and had routine laboratory investigations, including measurements of body mass index (BMI), haematocrit, lipid profile, and liver function tests (LFTs). Testosterone and PSA levels were assessed every 6–12 months. Patients with a biopsy‐confirmed or recent history of prostatitis before treatment were excluded. TRT was discontinued in men who developed prostate cancer.

RESULTS

Before and 36 months after treatment the total testosterone levels were 241.1 and 379.8 ng/dL (P < 0.05), respectively. Four men (4.9%) developed prostate cancer at a mean (range) of 32.5 (22–41) months after starting TRT. In men without prostate cancer (95.1%), PSA levels did not increase significantly at 1‐year intervals for 5 years. There was no statistical difference in PSA level change from baseline to 36 months when patients without prostate cancer were stratified into groups according to age (≤50, 55–65 and ≥70 years). In men with prostate cancer there was an increase in mean PSA level from baseline to 18 months of 1.8 ng/mL, and to 36 months of 3.2 ng/mL (P < 0.05). Total cholesterol improved from 203.8 to 166.6 mg/dL (P < 0.05) after 36 months of TRT; the BMI, haematocrit and LFTs did not change significantly.

CONCLUSIONS

LOH is an increasingly prevalent disease characterized by a symptomatically low testosterone level, and TRT is effective in normalizing serum testosterone levels, providing a beneficial cardiovascular effect, and improving sexual function and overall quality of life. PSA levels remain stable after normalization of testosterone for ≥5 years, prostate cancer can be effectively diagnosed and treated in men taking TRT, and the incidence of prostate cancer among men with LOH on TRT is no greater than that in the general population.     

Prostate specific-antigen distribution in asymptomatic Canadian men with no clinical evidence of prostate cancer

OBJECTIVE: To examine prostate specific-antigen (PSA) levels and percentage free/total PSA (f/tPSA) distributions as well as digital rectal examination (DRE) profiles in asymptomatic Canadian men with no established prostate cancer diagnosis, as recent data indicate that a man's risk of developing prostate cancer is higher if his baseline PSA level is above the median for his age group. SUBJECTS AND METHODS: We used data obtained during an early prostate cancer-detection event. An invitation to an onsite DRE, PSA level and f/tPSA assessment was accepted by 313 men. Serum PSA level and f/tPSA were measured before the DRE. A suspicious DRE and/or PSA level of > or = 2.5 ng/mL or f/tPSA of < or = 15% represented indications for a systematic 12-core ultrasonography-guided prostate biopsy. RESULTS: Of all the 313 men, most (235, 75%) had PSA levels of 0.01-1.53 ng/mL and an f/tPSA of >15% (285, 91.1%). The median (range) PSA level was 0.8 (0-34.2) ng/mL and f/tPSA was 27.4 (6.7-100)%. Age-specific median PSA levels and f/tPSA were, respectively, 0.7, 0.9, 1.0, 1.5 ng/mL and 31%, 27%, 26%, 25% for men aged 40-49, 50-59, 60-69 and 70-79 years. A suspicious DRE was recorded in 55 (17.6%) men, with eight (8.8%), 26 (20.0%), 14 (20.6%), and seven (28.9%) having suspicious DRE findings according to above age categories. Overall, seven (2.2%) prostate cancers were detected. CONCLUSION: The median age-specific baseline PSA levels and f/tPSA represent valuable indicators of prostate cancer risk. The population-specific baseline median PSA level should not be >1.0 ng/mL and the baseline f/tPSA should be >30%. Men with values outside of these ranges should be considered at greater risk of prostate cancer.     

Correlation between simultaneous PSA and serum testosterone concentrations among eugonadal, untreated hypogonadal and hypogonadal men receiving testosterone replacement therapy

The primary objective of this study was to correlate simultaneous measures of prostate-specific antigen (PSA) and serum testosterone among large samples of eugonadal, untreated hypogonadal and hypogonadal men treated with testosterone replacement therapy (TRT). From 2001 to 2007, laboratory records were reviewed to identify men who underwent simultaneous measurement of PSA and serum testosterone levels. The data were stratified based on three groups of men: group 1 consisted of eugonadal men (T>300 ng per 100 ml) evaluated for BPH, reproductive failure or sexual dysfunction; group 2 consisted of untreated hypogonadal men (T<300 ng per 100 ml); and group 3 comprised symptomatic hypogonadal men receiving TRT. Correlations were found between PSA (total and free fractions) and total serum testosterone levels among the three groups. Group 1: eugonadal men (n=385 patients), mean PSA and serum testosterone were 1.60 ng ml(-1) and 484 ng 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=-0.01, P=0.8). Group 2: untreated hypogonadal men (n=229 patients), mean PSA and serum testosterone were 1.49 ng ml(-1) and 269 ng per 100 ml, respectively. There was no significant correlation between PSA and total serum testosterone levels (r=0.03, P=0.6). Group 3: hypogonadal men on TRT (n=229 patients and 994 individual samples analyzed) mean PSA and serum testosterone were 1.50 ng ml(-1) and 555 ng per 100 ml, respectively. There was no significant correlation between PSA and serum testosterone levels (r=-0.005, P=0.9). Mean total serum testosterone levels were increased significantly (P<0.001) following treatment. Mean PSA levels did not increase in a statistically or clinically significant manner following TRT (mean PSA increase from baseline 0.05 ng ml(-1), P=0.6). In conclusion, TRT does not appear to significantly influence serum PSA expression and no significant correlation was identified between PSA and serum testosterone among eugonadal, untreated hypogonadal and hypogonadal men receiving TRT.     

Prostate-specific antigen testing in hypogonadism: implications for the safety of testosterone-replacement therapy

Hypogonadal men have lower prostate volumes and serum prostate-specific antigen (PSA) levels than age-matched controls. When present, prostate cancer in hypogonadal men is more aggressive than in eugonadal men, and given the lack of specificity of PSA for diagnosing prostate cancer, a more accurate test would be desirable in hypogonadal men. Once testosterone-replacement therapy is started in hypogonadal men, PSA levels should be measured regularly; however, there is often an initial rise 3-6 months after starting treatment. A rise of >0.5 ng/mL within this time requires further investigation.     

Problems with prostate specific antigen screening for prostate cancer in the primary healthcare setting in South Africa

OBJECTIVES: To assess the feasibility of detecting early-stage prostate cancer in the primary healthcare setting, and to investigate whether there is a higher incidence of prostate cancer in Black African men. PATIENTS AND METHODS: The study was a collaboration with registrars in the authors' institutions and primary healthcare centres serving mainly a Black African or mixed ancestry (Coloured) population in the semi-urban Cape Town metropolitan area of South Africa. Men aged 50-70 years attending the clinics were counselled about prostate cancer and invited to have a digital rectal examination (DRE), serum prostate-specific antigen (PSA) assay and transrectal ultrasonography-guided sextant prostate biopsy if the DRE was clinically suspicious of malignancy or the serum PSA was > or = 4.0 ng/mL. An American Urological Association Symptom Index (AUA-SI) was obtained, and urine analysed using dipsticks. RESULTS: From May 2000 to November 2001, 660 men were assessed (mean age 59.4 years, range 30-82); 60.6% were Black African, 37.3% mixed (Coloured), 1.8% White (Caucasian) and 0.2% Asian (Indian). The mean (range) AUA-SI was 5.98 (0-35) in the whole group; the DRE was recorded as clinically suspicious of malignancy in 3.2%. The mean PSA was 20.39 (0.04-10 000) ng/mL in the whole group, but when two outliers (1865 and 10 000 ng/mL) were disregarded, it was 2.4 ng/mL. In Black patients the mean PSA was 31.8 (0.04-10 000) ng/mL, and without the outliers, 2.1 ng/mL; in Coloured patients it was 2.94 (0.05-50) ng/mL. The PSA was > or = 4.0 ng/mL in 9.6% of the whole group, in 7.8% of Black and in 13% of Coloured patients. Prostate biopsies were taken in 21 patients (3.2% of the whole group and a third of those with a PSA of > or = 4.0 ng/mL); in Black patients, biopsies were taken in 1.5% and 19.4%, respectively, and in Coloured patients in 6.1% and 46.9%, respectively. The prostate biopsy showed cancer in 43% of the whole group, in a third of Black and in 47% of Coloured patients; prostate cancer was detected in 1.4%, 0.5% and 2.8%, respectively. CONCLUSIONS: That prostate biopsies were obtained in only 19% of Black and in only 47% of Coloured men with a serum PSA of > or = 4.0 ng/mL is of concern. This indicates that there is a significant problem in getting men with an elevated serum PSA level to undergo a prostate biopsy in the primary healthcare setting in South Africa.     

Elevated serum prostate specific antigen levels in conjunction with an initial prostatic biopsy negative for carcinoma: who should undergo a repeat biopsy?

OBJECTIVE: To determine the outcome of repeated prostatic biopsies in men attending with suspected prostate cancer but an initial negative biopsy. PATIENTS AND METHODS: Patients who had undergone two or more transrectal ultrasonography (TRUS)-guided prostate biopsies were identified from the Hospital Information Support System database. Indications for TRUS were a raised prostate-specific antigen (PSA) level (>4.0 ng/mL), with or without an abnormal digital rectal examination (DRE). Sextant prostate biopsies plus biopsies of any suspicious hypoechoic area or area of DRE abnormality were obtained for histology. Forty-eight patients underwent repeat TRUS-guided prostatic biopsies (mean age 67.5, sd 7. 25, range 53-82 years). RESULTS: The mean (sd, median, range) PSA level was 16.9 (13.5, 11.6, 5.2-61.8) ng/mL. Fifteen patients (31%) had carcinoma on repeat biopsy, 11 after the second and four after a third biopsy. The positive repeat biopsy rate was 24% where the PSA level was 4.0-9.9 ng/mL, 33% if the level was 10.0-19.9 ng/mL and 39% if it was >/=20.0 ng/mL. There was no significant difference in age or initial PSA concentration between those men with positive and those with negative repeat biopsies. However, patients with cancer had significantly higher PSA levels before repeat biopsy than at first biopsy (P=0.0043) and had greater PSA velocities than had patients with no diagnosis of cancer (P=0.0067). CONCLUSION: Where sufficient clinical suspicion exists, despite an initial negative biopsy, repeat TRUS-guided prostate biopsies should be carried out to exclude carcinoma of the prostate.     

Testosterone replacement therapy after primary treatment for prostate cancer

PURPOSE: A history of prostate cancer has been an absolute contraindication for testosterone supplementation. We studied a cohort of hypogonadal patients treated with radical retropubic prostatectomy (RRP) for organ confined prostate cancer to determine if testosterone replacement therapy (TRT) could be efficacious and administered safely without causing recurrent prostate tumor. MATERIALS AND METHODS: Ten hypogonadal patients previously treated with RRP for organ confined prostate cancer were identified. They presented with low serum total testosterone (TT) and symptoms of hypogonadism after RRP. Patients had baseline serum determinations of prostate specific antigen (PSA) and TT, and were started on testosterone supplementation. They were assessed periodically for changes in PSA and TT, and for symptomatic improvement using the hormone domain of the Extended Prostate Inventory Composite Health Related Quality of Life questionnaire. RESULTS: At a median followup of 19 months no patient had detectable (greater than 0.1 ng/ml) PSA. TT increased significantly after starting TRT from a mean +/- SD of 197 +/- 67 to 591 +/- 180 ng/dl (p = 0.0002). The Hormone Domain of the Extended Prostate Inventory Composite Health Related Quality of Life questionnaire increased significantly from 38 +/- 5 to 49 +/- 3 (p = 0.00005), primarily due to a decrease in hot flashes and an increase in energy level. CONCLUSIONS: At a median of 19 months of TRT hypogonadal patients with a history of prostate cancer had no PSA recurrence and had statistically significant improvements in TT and hypogonadal symptoms. In highly select patients after RRP TRT can be administered carefully and with benefit to hypogonadal patients with prostate cancer.     

Population-based screening for prostate cancer by measuring total serum prostate-specific antigen in Iran

OBJECTIVE: To report the results from an Iranian large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer. MATERIALS AND METHODS: A total of 3758 Iranian men older than 40 years were mass checked by PSA-based screening. Men with an abnormal digital rectal examination (DRE) and serum total PSA level of greater than 4 ng/mL, underwent transrectal ultrasonography (TRUS)-guided extended prostate biopsy. RESULTS: The PSA value (mean +/- standard deviation, SD) in all men without prostate cancer was 1.6 +/- 1.1 ng/mL and in those with cancer 18 +/- 44.8 ng/mL (P = 0.001). PSA values increased with age. In those aged 40-49, 50-59, 60-69 and > or = 70 years, the mean +/- SD PSA values were 1.3 +/- 0.7, 1.4 +/- 0.8, 1.8 +/- 1 and 2.2 +/- 1.6 ng/mL, respectively. Among the screened men, 323 (8.6%) had a serum PSA concentration greater than 4 ng/mL. Of patients who underwent prostate biopsy (230, 71.2%), 129 (positive predictive value, 56.1%) had prostate cancer. Additionally, nine cancers were detected among 16 patients with PSA of less than 4 ng/mL who had a doubtful DRE finding. The overall cancer detection rate was 3.6%; 1.4% at 40-49, 1.6% at 50-59, 4.2% at 60-69 and 12.9% at >/=70 years. Conventional systematic sextant biopsies, which accounted for six of the 10 cores in our biopsy scheme, detected 98 (71%) of the cancers. CONCLUSIONS: The Iranian male population develops prostate cancer quite commonly if their serum PSA levels are greater than 4.0 ng/mL. In this study, 65.9% of the detected cancers were clinically significant. The conventional systematic sextant technique may be inappropriate for detection of all prostate cancers. The results need to be confirmed in other randomized trials.     

Diagnostic value of serum prostate-specific antigen in hemodialysis patients

BACKGROUND: The value of serum prostate-specific antigen (PSA) screening was examined to detect prostate cancer in men receiving hemodialysis. METHODS: Forty-one male patients age 60-95 (median age, 70 years) receiving hemodialysis were investigated for PSA levels. We set the cut-off point at 4 ng/mL (the usual reference range). Digital rectal examination (DRE) and transrectal ultrasonography (TRUS) of the prostate were performed in patients whose PSA was more than 4 ng/mL and/or who expected further examination of the prostate. When prostate cancer was suspected, biopsy of the prostate was performed. In patients with prostate cancer, magnetic resonance imaging, computed tomography and bone scintigraphy were performed to diagnose the clinical stage. RESULTS: The mean serum level of PSA was 2.10 +/- 0.49 ng/mL. In this screening study, four of 41 men required further examinations for prostate cancer. Two of four refused further examinations. The other two were diagnosed with prostate cancer. The incidence of prostate cancer was at least 5% in our hemodialysis patients. One man, whose clinical stage was T2aN0M0, was treated with radical retropubic prostatectomy. Another man, whose clinical stage was T2bN0M0, was treated with luteinizing hormone-releasing hormone analogue. CONCLUSION: In our preliminary study, prostate cancer screening with PSA was useful for the early detection of prostate cancer in hemodialysis patients. If possible, DRE and TRUS should be performed in conjunction with PSA tests.     

Serendipity in detecting disease in low prostate-specific antigen ranges

OBJECTIVE: To assess the magnitude of prostate cancer detection by serendipity (the coincidental detection of prostate cancer during the evaluation of an abnormal screening test result) when a digital rectal examination (DRE) and transrectal ultrasonography (TRUS) are used as initial screening tests for prostate cancer in men with low levels of prostate-specific antigen (PSA; 0.0-3.9 ng/mL). PATIENTS AND METHODS: In all, 117 participants of a population-based screening study were diagnosed with prostate cancer after a standard evaluation of an abnormal screening test result; 49 underwent radical prostatectomy. Serendipity was defined as either: (i) the presence of prostate cancer opposite to the side that raised suspicion for cancer on DRE and/or TRUS; (ii) a negative lesion-directed biopsy while cancer was present in one or more of the cores of the sextant biopsy; (iii) a tumour volume of < 0.5 mL on radical prostatectomy. RESULTS: Depending on the definition, 27-63% of prostate cancers detected at low PSA values were detected coincidentally and not as a result of a true-positive test result. The proportion of cancers detected by serendipity was inversely correlated with serum PSA level. CONCLUSION: A relatively high proportion of prostate cancers diagnosed in men with low PSA levels, and in which a biopsy was prompted by a suspicious DRE and/or TRUS, are considered to be detected by chance only. As these cancers are mostly small (< 0.5 mL), with potentially low biological aggressiveness, relying on serendipity seems disadvantageous in prostate-cancer screening. The level of serendipity in prostate cancer detection, the poor performance of the screening test, and high inter-observer variability, casts further doubt on the utility of DRE (and TRUS) as initial screening tests for prostate cancer in population-based screening.     

Age, prostate-specific antigen, and digital rectal examination as determinants of the probability of having prostate cancer

Objectives. The decision to perform prostate biopsy has traditionally been based on an abnormal prostate-specific antigen (PSA) level or abnormal digital rectal examination (DRE) findings. For example, a 60-year-old man with a benign DRE and PSA level of 4.1 ng/mL would be counseled for biopsy, and the same man with a PSA level of 3.9 ng/mL might be counseled against biopsy. However, the difference in these PSA levels and in the likelihood of these two men having prostate cancer is not significant. We constructed a probability nomogram for the likelihood of detecting prostate cancer, thus aiding in the decision of whether to perform a prostate biopsy.Methods. Using multivariate logistic regression analysis and data from 2054 men (mean age 64 years) participating in the Tyrol Screening Project between January 9, 1993 and January 9, 1997, patient age, PSA level, and DRE findings were analyzed for their ability to determine the likelihood of finding prostate cancer on transrectal ultrasound-guided biopsy.Results. DRE was suspicious in 278 men (13.5%). Overall, 498 (24.5%) of 2054 men biopsied had prostate cancer. The probability of discovering cancer on biopsy was calculated using patient age, DRE findings, and PSA level.Conclusions. DRE status had a large influence on the likelihood of positive biopsy across all PSA and age ranges. A combination of PSA, DRE result, and age better defined the probability of a positive biopsy than any factor alone. Using this nomogram, the decision to proceed with or defer prostate biopsy can be based on an actual probability of discovering prostate cancer rather than a single PSA-based cutpoint. These data may aid physicians and patients in decision-making.     

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.     

Is a digital rectal examination necessary in the diagnosis and clinical staging of early prostate cancer?

OBJECTIVE: To assess the role of a digital rectal examination (DRE) in the clinical diagnosis of prostate cancer and in predicting the pathological stage, as the diagnosis of early prostate cancer usually comprises prostate-specific antigen (PSA) testing, a DRE and transrectal ultrasonography (TRUS)-guided biopsies. PATIENTS AND METHODS: Over the 4 years between 2000 and 2004, 408 consecutive patients (mean age 63.8 years) referred with age-specific PSA levels of 2.5-10.0 ng/mL and who had a TRUS-guided 12-core prostate biopsy were included in the study. They had a DRE by either of two experienced consultant urologists. The results of the DRE and core biopsy histology were compared with the histology and the radical prostatectomy specimen in a subset (82 men) of the study population. RESULTS: Cancer was detected on biopsy in 152 patients; of the 196 with an abnormal DRE, 47% had cancer on biopsy. In the patients with a normal DRE, 59 cancers were detected. Men with cancer were older and had a higher median PSA level. There was no correlation between the DRE and biopsy findings, and none between an abnormal DRE and histological diagnosis of cancer. Of the patients who had a radical prostatectomy, 38% had a normal DRE. CONCLUSION: There was no correlation between the DRE, biopsy findings and pathological staging. The DRE did not contribute to managing patients with prostate cancer, but this does not mean that there is no longer a place for the DRE in assessing the urological patient. If patients are appropriately counselled before PSA testing, a DRE may not be essential for patients with a PSA level of 2.5-10 ng/mL.     

Testosterone administration to men with testosterone deficiency syndrome after external beam radiotherapy for localized prostate cancer: preliminary observations

OBJECTIVE

To assess the effects of testosterone supplementation in men with testosterone deficiency syndrome (TDS) after external beam radiotherapy (EBRT) for localized prostate cancer.

PATIENTS AND METHODS

Five men with significant signs of TDS after treatment for localized prostate cancer with EBRT were treated with testosterone once their prostate‐specific antigen (PSA) level had reached the nadir.

RESULTS

The mean (range) level of testosterone before supplementation was 5.2 (1.1–9.2) nmol/L and the duration of follow‐up while on supplementation was 14.5 (6–27) months. At the last visit, the testosterone levels were 17.6 (8.5–32.4) nmol/L. One of the five patients had a transitory increase in PSA level but none had levels of >1.5 ng/mL. All patients reported a marked response in the manifestations of TDS, i.e. four each reported decreased hot flushes, decreased fatigue and improved libido, and two reported improved erectile function.

CONCLUSION

Men with TDS after EBRT for localised prostate cancer are candidates for testosterone therapy. The patients must be aware of the advantages and disadvantages of the treatment. PSA levels must have reached a nadir before starting treatment and the follow‐up must be particularly close. In these few patients there were no adverse effects from testosterone supplementation. There is a need for more information about the safety and efficacy of testosterone therapy in men successfully treated for localized prostate cancer, because there is evidence indicating hypogonadism in these patients, compromising their quality of life and longevity, independent of the cancer.     

Are prostatic biopsies necessary in men aged > or =80 years?

OBJECTIVE: To examine whether prostatic biopsies are necessary in all men aged > or =80 years, as men found to have prostate cancer are frequently treated with a 'watch and wait' policy or with hormonal withdrawal alone, and biopsies are associated with a small but significant complication rate. PATIENTS AND METHODS: The findings on a digital rectal examination (DRE), the prostate-specific antigen (PSA) level, the biopsy and staging bone scan results for all men aged > or = 80 years who had prostatic biopsies over a 3-year period were reviewed, together with those in a group of men aged <80 years for comparison. All biopsy samples had been examined in one of three histopathology units, and 33 consultant urological surgeons contributed. RESULTS: In all, 210 biopsies from 205 men aged > or = 80 years were identified, of whom 163 (79%) had biopsy-confirmed prostate cancer. All 29 men with a PSA level of > or = 100 ng/mL, 98% of 47 with > or = 50 ng/mL, 97% of 76 with > or = 30 ng/mL and 92% of 101 with > or = 20 ng/mL had biopsy cores containing cancer; 63% of men with a PSA level of <20 ng/mL had cancer on biopsy. In men with cancer and a PSA level of > or = 30 ng/mL, 92% had Gleason grade > or = 7 and 93% were treated with hormonal withdrawal alone. In all men with cancer the DRE was abnormal in 91%, the mean number of positive cores was 59% and the bone scan was positive in 18%. The DRE was abnormal in 77% of men with benign biopsies. CONCLUSIONS: In men aged > or = 80 years with a PSA level of > or = 30 ng/mL, at least 97% had prostate cancer, >90% of whom had high-grade disease, and nearly all with cancer received active pharmacological treatment. In the vast majority of these men prostate biopsies did not alter their cancer management. The value of prostatic biopsy in this age group, with a PSA level of > or = 30 ng/mL, is questionable.     

Adenocarcinoma of the prostate in men younger than 40 years of age: diagnosis and treatment with emphasis on radical prostatectomy findings

Objectives. Prostate cancer is rarely diagnosed in men younger than 40 years of age. It is thought, although not documented, that these tumors behave particularly aggressively.Methods. We studied 87 men younger than 40 years old who underwent prostate needle biopsy and were from three populations: (a) 71 cases (63 benign, 7 cancer) from Dianon Systems; (b) 9 needle biopsies with cancer sent to one of us (J.I.E.) in consultation; and (c) 7 men with cancer who came to Johns Hopkins for consultation.Results. The median age of men with a benign biopsy was 35 years (mean 33.9, range 22 to 39); the median age of men with cancer was 38 years (mean 35.9, range 22 to 39) (P = 0.004). The most common indications for biopsy were abnormal digital rectal examination (DRE) (n = 61); elevated prostate-specific antigen (PSA) (n = 14), and inflammatory symptoms (n = 12). Other reasons cited included hematuria, abnormal ultrasound, pain, ejaculatory problems, obstructive symptoms, and family history of prostate cancer. The median PSA was 2.6 ng/mL (mean 4.8, range 0.3 to 66) for all men, 1.2 ng/mL (mean 3.4, range 0.3 to 19.9) for benign cases, and 4.4 ng/mL (mean 8.7, range 2.1 to 66) for cancer (P = 0.0004). Abnormal DRE was not predictive of cancer. Of the 55 patients whose family history was known, 40 men had no family history of prostate cancer, and of those, only 6 (15%) had cancer. Of the 15 patients with a family history of cancer, 6 (40%) were found to have cancer on biopsy (P = 0.05). Of the 23 patients with cancer, 3 were lost to follow-up, 1 was treated with hormones, and 3 chose watchful waiting. The remaining 16 patients underwent radical prostatectomy and had diverse pathologic findings. Tumor volume ranged from 0.01 to 6.35 cc. Pathologic stage was pT2 in 9 cases and pT3 in 7 cases (2 with positive pelvic lymph nodes). In 14 men, serum PSA values were available: of 4 men with PSA greater than 10 ng/mL, all had Stage pT3, and of 10 men with PSA less than 10 ng/mL, 3 had Stage pT3.Conclusions. Young men who are candidates for radical prostatectomy have potentially curable disease, particularly if PSA at the time of diagnosis is less than 10 ng/mL.     

Testosterone as a predictor of pathological stage in clinically localized prostate cancer

PURPOSE: Substantial controversy exists in the literature regarding the association between pretreatment testosterone and disease outcome in patients with prostate cancer. We explored the relationship between preoperative total testosterone, and pathological stage and progression in patients with clinically localized prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed the records of consecutive patients with clinically localized prostate cancer treated with radical prostatectomy between January 1990 and June 2003. A total of 326 patients with pretreatment testosterone levels available were eligible for this analysis. Biochemical progression (BCR) was defined by postoperative prostate specific antigen (PSA) greater than 0.4 ng/ml with a confirmatory increase and it occurred in 41 men. No men received adjuvant therapy. Univariate and multivariate logistic regression analyses were done to examine whether pretreatment testosterone was associated with pathological stage. Cox regression was used to assess the association of testosterone and BCR. RESULTS: Median PSA was 6.01 ng/ml (range 0.13 to 86), testosterone was 385 ng/dl (range 133 to 998) and followup was 36 months (range 4 to 136). In 245 patients (75%) disease was organ confined. Lower testosterone correlated with adverse pathological stage on multivariate analysis (p = 0.01), as did clinical stage, biopsy grade and PSA. However, we found no relationship between testosterone and BCR after adjusting for covariates. Furthermore, we found no evidence of an interaction between PSA and testosterone (p = 0.4). CONCLUSIONS: On multivariate analysis low preoperative total testosterone was associated with advanced pathological stage but not with BCR. Future studies are warranted with data on more patients who have progressed.     

Influence of demographic factors and biochemical characteristics on the prostate-specific antigen (PSA) response to testosterone replacement therapy

A retrospective study was performed to evaluate how the prostate-specific antigen (PSA) response to testosterone replacement therapy (TRT) varies with age, mode of testosterone treatment, and baseline levels of PSA and testosterone. In total, 48 consecutive hypogonadal men who completed 1 year of TRT were evaluated. All men had a negative prostate biopsy obtained prior to initiating TRT. Men received TRT in the form of intramuscular injections (n = 33) or topical gel (n = 25) based on clinical response. Comparisons in the change in PSA after 1 year of TRT were made based on various thresholds for age and baseline values of PSA, total testosterone (TT), and free testosterone (FT). Baseline levels of TT (297.7+/-156.6 vs 292.7+/-89.7 ng/dl; P = 0.88) and FT (0.95+/-0.3 vs 1.1+/-0.3 ng/dl; P = 0.08) were similar for the injection and transdermal groups, and both groups also had similar baseline PSA values (1.92+/-1.9 vs 1.71+/-1.9 ng/ml, respectively; P = 0.67). After 1 year of TRT, mean PSA values did not differ significantly between groups, nor did the mean increase in PSA (P > 0.05). The overall mean increase in PSA was 0.31+/-0.76 ng/ml. After one year of TRT, PSA was decreased in 21%, unchanged in 22%, and increased in 57%. Only 24% of the entire group demonstrated a PSA increase of 0.5 ng/ml or greater. No statistical difference was found in the change in PSA based on patient age, baseline PSA levels, or baseline levels of TT or FT. TRT causes only a mild increase in PSA in most hypogonadal men, and does not appear to be influenced by the mode of TRT, age, or baseline levels of PSA or testosterone.