Ove Gustafsson

Lead time associated with screening for prostate cancer

Screening serum levels of prostate‐specific antigen (PSA) is now a major strategy for early detection of prostate cancer (PC). Quantification of the lead time thus obtained is important both for understanding the development of PC and for evaluating the advantages and disadvantages of widespread screening. In our study, 1,233 randomly selected men living in Stockholm in 1988 were invited to participate in an early detection (ED) program, in which suspicious findings provided by digital rectal examination (DRE), transrectal ultrasonography (TRUS) and/or a PSA value ≥10.0 ng/mL were followed up by biopsy. The cumulative incidence (Kaplan‐Meier) of PC in the 946 participants (ED) during 12 years of follow‐up was compared to that of an age‐matched, randomly selected reference population (RP) of 657 men for whom PSA values (from frozen serum samples) could also be obtained. The PC incidence in men in the RP with PSA values ≥3.0 ng/mL reached the corresponding level for the ED group after 10.6 years (the “catch‐up” point). After 12 years of follow‐up, the estimated median lead time for men with PSA values in this interval was 4.5 years in the ED population, compared to 7.8 years in the RP. With 20 years of follow‐up, the estimated median lead time of the RP was enhanced to 10.7 years. The lead time in connection with PC was influenced by the initial PSA level (although with large variations), length of follow‐up and sensitivity of the ED procedure employed. The ED program described here was not associated with major overdetection.

Diagnostic Methods in the Detection of Prostate Cancer: A Study of a Randomly Selected Population of 2,400 Men

We investigated the value of digital rectal examination, transrectal ultrasonography and prostatic specific antigen (PSA) analysis as aids in general clinical practice and in the early detection of prostate cancer. Of a randomly selected population of 2,400 men 55 to 70 years old who were offered examination with digital rectal examination, transrectal ultrasound and PSA analysis, 1,782 (74%) accepted and prostate cancer was detected in 65 (3.6%). When the transrectal ultrasound results were also considered the detection rate of digital rectal examination (2.3%) was increased by 50% and the number of stage T2A or less tumors was doubled. At reexamination due to markedly high PSA values (7 micrograms/l. or more) only a few additional cancers (5%) were detected. However, it is noteworthy that 80% of the detected cancers were found among the subgroup with abnormal PSA values (4 micrograms/l. or more) and comprising 17% of the study population, which suggests the possibility of selecting a risk group at mass screening. Moreover, the positive predictive value increased from 4% (when only digital rectal examination was positive) to 71% for the combination of positive digital rectal examination, positive transrectal ultrasound and an increased PSA concentration (that is 7 micrograms/l. or greater).

15-year followup of a population based prostate cancer screening study.

PURPOSE We evaluated long-term survival in attendees and nonattendees of a 1-time screening for prostate cancer. MATERIALS AND METHODS A total of 2,400 men 55 to 70 years old in 1988 were randomly selected and invited to a screening for prostate cancer. Of the invited men 1,782 (74%) attended. Screening attendees were examined with digital rectal examination, transrectal ultrasound and prostate specific antigen analysis. When cancer was suspected, prostate biopsies were taken. A total of 65 men with prostate cancer were detected by this procedure. The entire source population comprising 27,204 men, including 618 nonattendees (26%), was followed for prostate cancer diagnosis and survival for 15 years. RESULTS Incidence rate ratios were calculated using Poisson regression models. We found no effect of this screening procedure on the risk of death from prostate cancer and other causes of death (incidence rate ratio 1.10, 95% CI 0.83-1.46 and 0.98, 95% CI 0.92-1.05, respectively) when comparing all invited men with the source population. However, attending the screening program was associated with a significantly decreased risk of death from causes other than prostate cancer (vs source population incidence rate ratio 0.82, 95% CI 0.76-0.90). In contrast, the corresponding incidence rate ratio in nonattendees was 1.53 (95% CI 1.37-1.71). CONCLUSIONS We found no evidence of a beneficial effect of this specific screening procedure but strong evidence of a difference in overall survival in screening attendees and nonattendees. These findings should be considered when interpreting previous and upcoming studies of the effect of screening programs.

Follow-up of Prostate Cancer Patients by On-demand Contacts with a Specialist Nurse: A Randomized Study

Objective: The effectiveness of traditional follow-up programs and the intensive search for disease progression in men with prostate cancer have been questioned. The aims of this randomized multi-centre study were to evaluate medical safety, patient satisfaction and resource utilization in an on-demand follow-up by a specialist nurse compared with traditional follow-up by a urologist. Material and methods: Four hundred consecutively approached men with newly diagnosed or previously known prostate cancer in any stage at three hospitals in Sweden were randomized to follow-up in the nurse group (NG, 200 patients) or the urologist group (UG, 200 patients). In the NG, the nurse contacted the patient by phone every 6 months unless the patient himself initiated the contact. Patient satisfaction was evaluated twice a year via questionnaire. The questionnaire included the validated Hospital Anxiety and Depression Scale (HADS). The costs of all medical interventions and adverse events related to prostate cancer were calculated for all patients. Results: Medical safety, measured as complication frequency and lag time from symptoms to intervention, during the first 3 years of the observation period, was similar in the NG and the UG. The total number of interventions due to symptoms from prostate cancer was also similar in both groups. The analysis of accessibility and the HAD scale showed no significant differences between the groups. The mean outpatient cost (excluding pharmaceutical costs) per patient was lower in the NG compared to the UG, especially among patients without metastases at inclusion (37% lower cost). Conclusions: Our study indicates that men with prostate cancer can be safely followed up by a specialist nurse. The study results show that this alternative follow-up is cost-effective, especially in men without metastases.

Open retropubic prostatectomy versus robot-assisted laparoscopic prostatectomy: A comparison of length of sick leave

Objective. It remains uncertain whether the increased direct costs of robot-assisted laparoscopic radical prostatectomy (RALP) are outweighed by cost savings due to shorter postoperative hospital care and shorter sick leave. This study compared the length of sick leave after RALP with that after radical retropubic prostatectomy (RRP). Material and methods. In a cohort study, information on length of sick leave was retrieved for 274 working men undergoing radical prostatectomy (127 RALP and 147 RRP). Data on confounders such as physical workload, average salary, body mass index and disease characteristics were collected from the medical records. Cox regression models were used to compare the treatment groups. Results. The median number of days with sick leave was 11 in the RALP group and 49 in the RRP group. After adjustment for confounders, patients in the RALP group were twice as likely to return to work at any time during follow-up (hazard ratio = 2.13, 95% confidence interval 1.62–2.80). High physical workload, low salary and high tumour grade were more common in the RRP group and associated with longer sick leave. Conclusions. Patients in the RALP group had shorter postoperative hospital stay and less need for paid sick leave than patients in the RRP group. These data indicate that RALP shortens the convalescence. Part of this difference may, however, be attributable to different selection of patients and different a priori expectations among patients and their doctors. A prospective randomized study is advocated, although blinding is unfeasible.

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.

Radical prostatectomy: Influence on serum and urinary androgen levels

The role of the prostate as an active endocrine organ and the hormonal changes after radical prostatectomy (RP) has not been well studied. The objective of this study was to investigate the serum and urine hormonal changes after RP.

Short-term Results after Robot-assisted Laparoscopic Radical Prostatectomy Compared to Open Radical Prostatectomy

BACKGROUND Robot-assisted laparoscopic radical prostatectomy has become a widespread technique despite a lack of randomised trials showing its superiority over open radical prostatectomy. OBJECTIVE To compare in-hospital characteristics and patient-reported outcomes at 3 mo between robot-assisted laparoscopic and open retropubic radical prostatectomy. DESIGN, SETTING, AND PARTICIPANTS A prospective, controlled trial was performed of all men who underwent radical prostatectomy at 14 participating centres. Validated patient questionnaires were collected at baseline and after 3 mo by independent health-care researchers. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The difference in outcome between the two treatment groups were analysed using logistic regression analysis, with adjustment for identified confounders. RESULTS AND LIMITATIONS Questionnaires were received from 2506 (95%) patients. The robot-assisted surgery group had less perioperative bleeding (185 vs 683 ml, p<0.001) and shorter hospital stay (3.3 vs 4.1 d, p<0.001) than the open surgery group. Operating time was shorter with the open technique (103 vs 175 min, p<0.001) compared with the robot-assisted technique. Reoperation during initial hospital stay was more frequent after open surgery after adjusting for tumour characteristics and lymph node dissection (1.6% vs 0.7%, odds ratio [OR] 0.31, 95% confidence interval [CI 95%] 0.11-0.90). Men who underwent open surgery were more likely to seek healthcare (for one or more of 22 specified disorders identified prestudy) compared to men in the robot-assisted surgery group (p=0.03). It was more common to seek healthcare for cardiovascular reasons in the open surgery group than in the robot-assisted surgery group, after adjusting for nontumour and tumour-specific confounders, (7.9% vs 5.8%, OR 0.63, CI 95% 0.42-0.94). The readmittance rate was not statistically different between the groups. A limitation of the study is the lack of a standardised tool for the assessment of the adverse events. CONCLUSIONS This large prospective study confirms previous findings that robot-assisted laparoscopic radical prostatectomy is a safe procedure with some short-term advantages compared to open surgery. Whether these advantages also include long-term morbidity and are related to acceptable costs remain to be studied. PATIENT SUMMARY We compare patient-reported outcomes between two commonly used surgical techniques. Our results show that the choice of surgical technique may influence short-term outcomes.

Prostate-specific Antigen (PSA), PSA Density and Age- adjusted PSA Reference Values in Screening for Prostate Cancer A Study of a Randomly Selected Population of 2,400 Men

Prostate cancer screening with DRE, TRUS, and PSA testing was offered to 2,400 randomly selected men 55-70 years old. Among 1,782 examined, 65 (3.6%) men with prostate cancer were diagnosed. The PSA results were correlated to the diagnosis, the mens age, and the prostate volume. Least square regression analysis was used to calculate the 95% upper confidence intervals for PSA in each year of age in men without prostate cancer. The PPV was calculated for: (i) PSA > 4 ng/ml, (ii) PSAD > 0.15, (iii) PSAD > 0.20 and (iv) age-adjusted PSA reference values. A significant correlation was found between PSA and prostate volume, between PSA and age, and between the prostate volume and age. The calculated annual growth of the prostate was 1.6% and the annual increase in PSA was 2.4%. The age-adjusted upper PSA reference values for the three age categories studied (55-59, 60-64 and 65-70 years) were 5.2, 5.8, and 6.7 ng/ml, respectively. The PPVs for PSA > 4 ng/ml, PSAD > 0.15, PSAD > 0.20, and the age-adjusted PSA reference values were 17%, 14%, 22%, and 27%, respectively. Age-adjusted PSA or PSAD may increase the PPV compared to PSA > 4 ng/ml. The detection rate is, however, inadequate. A PSA cut-off at 4 ng/ml could therefore be maintained in men 55-70 years old. The median PSA values and median prostate volumes calculated for men with benign findings may serve as a reference in future studies.

Correlation between circulatory, local prostatic, and intra-prostatic androgen levels.

Testosterone is converted to the more potent androgen dihydrotestosterone (DHT) in the prostate. DHT and androgen metabolites are inactivated by uridine diphospho (UDP)‐glucuronosyl transferase (UGT) enzymes. Here we have studied the influence of the prostate gland on the systemic levels of DHT. Moreover, genetic variation in androgen metabolizing UGT enzymes and the intra‐prostatic levels of glucuronidated DHT metabolites were investigated.