The significance of clinically insignificant residual fragments after percutaneous nephrolithotomy: an analysis into the relevance of complete stone clearance.

PURPOSE: After treatment for kidney stones, residual fragments with a diameter of ≤ 4 mm are traditionally referred to as 'clinically insignificant residual fragments'. We hypothesize that patients with these fragments are at an increased risk for stone-related morbidity, such as complaints, hydronephrosis, and stone regrowth, when compared to stone-free patients. This study aimed to investigate the relevance of complete stone clearance in surgical treatment of urolithiasis. METHODS: We conducted a single-center retrospective cohort study. Patients who underwent percutaneous nephrolithotomy between 2015 and 2020 were included if a CT-scan was available within 6 months after the procedure, and the follow-up duration was at least 1 year. The stone-free status at the end of the first stone episode during the study period was categorized as fully stone-free, not stone-free with small residual fragments (≤ 4 mm) and not stone-free with large residual fragments (> 4 mm). Follow-up data were collected, including stone-related events and re-intervention rates. RESULTS: A total of 103 subjects were included with a median follow-up of 21.4 months. Stone-related events occurred in 10 (29.4%) of the fully stone-free subjects, 20 (58.8%) of the subjects with small residual fragments and 25 (71.4%) of the subjects with large residual fragments. The stone-related event-free survival per subgroup resulted in a significantly different survival distribution in a log rank test (p = 0.008). CONCLUSION: A complete stone-free status seems to be of fundamental importance for decreasing stone-related morbidity. Further developments and research should focus on optimizing the full clearance of stone material during PCNL.

Cone Beam Computed Tomography-Assisted Percutaneous Nephrolithotomy in a Hybrid Operating Room: Optimization of Patient Selection.

Background: Cone beam computed tomography (CBCT) enables intraoperative cross-sectional and three-dimensional imaging of the urinary tract. CBCT in a hybrid operating room can be used for intraoperative detection of residual stones and potential additional stone extraction at the end of percutaneous nephrolithotomy (PCNL). This study describes our initial experience with intraoperative CBCT during PCNL and analyzes its role in potentially improving its outcomes. Methods: We conducted a single-center retrospective cohort study at a tertiary referral hospital between 2018 and 2021. The study aimed to evaluate the outcome of patients who underwent intraoperative noncontrast CBCT scan during PCNL. The CBCT scan was performed when the urologist determined the kidney to be endoscopically stone-free. In case any residual fragments were imaged, an additional effort was made to extract them. Patients were divided into three groups based on treatment outcome: stone-free upon CBCT, not stone-free with additional stone extraction after CBCT, and not stone-free without additional stone extraction. Procedure and patient characteristics were recorded to identify factors associated with additional stone extraction during CBCT-assisted PCNL. Results: A total of 102 procedures were included in this study. Intraoperative CBCT scans showed residual calcifications in 58 (57%) cases. In 39 cases, which is 38% of the total population and 61% of the cases with residual calcifications, one or more residual fragments imaged on the intraoperative CBCT-scan were extracted additionally within the same procedure. A higher Guy's Stone Score was associated with a higher likelihood of additionally extracting stones as a result of the CBCT. Conclusions: CBCT-assisted PCNL in a hybrid operating room can lead to additional stone extraction in the same procedure in 37% of all cases and in over 60% of the cases in which residual fragments are imaged. The value of CBCT-assisted PCNL appears to increase in the case of more complex stone surgery cases.

End-fire versus side-fire: a randomized controlled study of transrectal ultrasound guided biopsies for prostate cancer detection.

Objectives: To compare prostate cancer detection rates between end-fire and side-fire ultrasound guided prostate biopsy techniques.Methods: A prospective randomized controlled trial was performed in patients who underwent prostate biopsy between 2009 and 2014. Patients were randomly assigned to the end-fire or side fire biopsy groups and underwent transrectal ultrasound guided prostate biopsy. The overall prostate cancer detection rate was compared between the two probe configurations. Trial was registered at Clinical Trials.gov with identifier: NCT00851292.Results: A total of 730 patients were included and randomized, 371 patients underwent prostate biopsy with side-fire probe and 359 patients with the end-fire probe. Prostate cancer detection rates were 52.4% in the end fire group and 45.6% in the side fire group (p = .066).Conclusions: No significant difference was found in detection rate of prostate cancer between the end-fire and side-fire probe in transrectal ultrasound guided prostate biopsy, neither for detection rate of prostate cancer in the apex.

Effect of the correction for noncompliance and contamination on the estimated reduction of metastatic prostate cancer within a randomized screening trial (ERSPC section Rotterdam).

The European Randomized study of Screening for Prostate Cancer (ERSPC) has recently reported a 20% reduction in death from prostate cancer in a population-based prostate cancer screening (core age group: 55-69 years of age). The effect of screening may be diluted by noncompliance in the screening arm and contamination by PSA testing in the control arm. The purpose is to analyze the effect of prostate cancer screening on the incidence of metastatic prostate cancer, both with and without adjustment for noncompliance and contamination. We analyzed the occurrence of metastases in 42,376 men aged 55-75 years who were randomized in the Rotterdam section of the ERSPC between 1993 and 1999. Contamination adjustment was based on follow-up findings and questionnaire data from all men in the control group who developed prostate cancer and from a random sample of 291 men without cancer who had a PSA test. Prostate cancer screening significantly reduced the occurrence of metastatic prostate cancer in the intention-to-screen analysis [RR 0.75, 95% CI 0.59-0.95, p = 0.02] and more so in adjusted analyses; contamination adjusted RR 0.73, 95% CI 0.56-0.96; noncompliance adjusted RR 0.72, 95% CI 0.55-0.95 and fully adjusted analysis RR 0.68, 95% CI 0.49-0.94, p = 0.02. In the population of ERSPC Rotterdam (N = 42,376 men), screening reduces the risk to be diagnosed with metastatic prostate cancer considerably on population level, an effect which is even more pronounced in men who are in fact screened.

Short-term outcomes of the prospective multicentre 'Prostate Cancer Research International: Active Surveillance' study.

OBJECTIVE: To evaluate the short-term outcomes of the prospective international Prostate Cancer Research International: Active Surveillance ('PRIAS') study (Dutch Trial Register NTR1718), as active surveillance (AS) for early prostate cancer might provide a partial solution to the current overtreatment dilemma in this disease. PATIENTS AND METHODS: The first 500 (of >950) participants with asymptomatic T1c/T2 prostate cancer, with a prostate-specific antigen (PSA) level of < or =10.0 ng/mL, a PSA density of <0.2 ng/mL/mL, a Gleason score of < or =3 + 3 = 6, and one or two positive biopsy cores, were analysed. The follow-up protocol consisted of frequent PSA measurements, digital rectal examinations, and standard repeat biopsies (the first after 1 year). The primary outcome is survival free of active therapy; the secondary endpoints are reasons for stopping AS, findings in 1-year repeat biopsies, and outcomes after radical prostatectomy (RP). RESULTS: Patients were included between December 2006 and July 2008. The median (25-75th percentile) follow-up after diagnosis was 1.02 (0.6-1.5) years. The 2-year survival rate free from active therapy was 73%. Of the 82 men who changed to active therapy during the follow-up, 68 (83%) did so based on the protocol. Of the 261 repeat biopsies available for analysis, 90 (34%) showed no cancer, while 57 (22%) showed a Gleason score of >6 or more than two positive biopsy cores. There was a relatively unfavourable PSA doubling time of 0-10 years in 53% (102/194) and 62% (33/53) of men with favourable and unfavourable re-biopsy results, respectively. After RP, four of 24 (17%) men had T3 disease and 12 (50%) had a Gleason score of >6. CONCLUSION: AS seems feasible, but mortality outcomes are unknown. A strict follow-up protocol including standard 1-year repeat biopsies resulted in a quarter of men stopping AS after 2 years.

[The need for orchiopexy in the case of congenital undescended testis]. / De noodzaak van orchidopexie bij congenitale niet-scrotale testis.

Congenital undescended testis (UDT) is a common congenital anomaly among males. Since ectopic position of the testis is considered a risk factor for the development of testicular cancer and infertility, early diagnosis and treatment are essential. Careful physical examination after birth should indicate those patients with UDT who must be followed up for possible orchiopexy at an early age. Treatment consists of performing orchiopexy at the age of 6-12 months to reduce the risk of malignancy and/or infertility. Despite the necessity of treating UDT, isolated cases of intra-abdominal seminoma are found. In patients with abdominal complaints and UDT, the possibility of problems due to this condition must be considered. In the present case, a patient with an intra-abdominal seminoma in the presence of unilateral UDT is presented.

Gleason score 7 screen-detected prostate cancers initially managed expectantly: outcomes in 50 men.

OBJECTIVE To assess whether men newly diagnosed with Gleason 7 prostate cancer are eligible for active surveillance (AS) instead of radical treatment. AS is an appropriate initial strategy in selected men who are presently diagnosed with prostate cancer, as many tumours will not progress during a patient's lifetime. PATIENTS AND METHODS Cancer-specific-, overall and treatment-free survival were analysed retrospectively in men with Gleason score 7 cancer who were initially managed expectantly. All were screen-detected in four centres of the European Randomized Study of Screening for Prostate Cancer. RESULTS In 50 men active therapy was initially withheld if they had Gleason 7 disease; 29 of 50 (58%) would otherwise have been suitable for AS, as they had a prostate-specific antigen (PSA) level of < or =10.0 ng/mL, a PSA density of <0.2 ng/mL/mL, stage T1c/T2, and two or fewer positive biopsy-cores; 44 of 50 (88%) had a Gleason score 3 + 4 = 7. The mean (range) age of the men was 69.5 (59.6-76.2) years and the median (interquartile range) follow-up was 2.6 (0.8-5.0) years; the mean American Society of Anesthesiologists score was 1.8. The 6-year cancer-specific survival (nine patients at risk) was 100%, which sharply contrasted with the 68% overall survival. Men alive at the time of analysis had a favourable PSA level and PSA-doubling time. The 6-year treatment-free survival was only 59%, with most patients switching to active therapy, justified on the basis of their PSA level. However, men with otherwise favourable tumour characteristics and a Gleason score of 3 + 4 = 7 remained treatment-free significantly longer than their counterparts with unfavourable other tumour features and a Gleason score of 4 + 3 = 7. CONCLUSION In selected patients with screen-detected Gleason 3 + 4 = 7 prostate cancer, AS might be an option, especially in those with comorbidity and/or a short life-expectancy.

Outcomes of men with screen-detected prostate cancer eligible for active surveillance who were managed expectantly.

BACKGROUND: The incidence of small, localised, well-differentiated prostate cancer (PCa) is increasing, mainly as a result of screening. Many of these cancers will not progress, and radical therapy may lead to substantial overtreatment. Active surveillance (AS) has emerged as an alternative. OBJECTIVE: To retrospectively validate the currently used criteria for eligibility for AS. DESIGN, SETTING, AND PARTICIPANTS: For this cohort study, data from 616 men who were diagnosed with PCa between 1994 and 2007 at a mean age of 66.3 yr in four centres of the European Randomized Study of Screening for Prostate Cancer (ERSPC) were combined. All patients fit the criteria for AS (prostate-specific antigen [PSA] < or = 10.0 ng/ml, PSA-density < 0.2 ng/ml per ml, stage T1C/T2, Gleason score < or = 3 + 3 = 6, and < or = 2 positive biopsy cores), and initially they were managed expectantly. Median follow-up was 3.91 yr. MEASUREMENTS: Disease specific-, overall-, and treatment-free survival were studied. Present PSA characteristics were assessed and also compared between men who were switching to deferred active therapy during follow-up and men remaining untreated. RESULTS AND LIMITATIONS: The calculated (Kaplan-Meier) 10-yr PCa-specific survival (21 patients at risk) was 100%, which sharply contrasted with 77% overall survival. Men still alive showed favourable PSA characteristics. Although the calculated 10-yr treatment-free survival was only 43%, objective signs of progression often did not indicate the shift to radical treatment. The cohort consisted of men on AS and those on watchful waiting (WW); information on comorbidity or psychological distress was not available. CONCLUSIONS: AS seems justified in selected men with screen-detected PCa. Prospective protocol-based AS programs are necessary to optimise selection criteria and to find the appropriate trigger points for switching to active therapy. Possible negative psychological reactions with AS against improved quality of life by withholding side-effects from radical treatment should be considered.

Prostate-specific antigen kinetics in clinical decision-making during active surveillance for early prostate cancer--a review.

CONTEXT: The kinetics of prostate specific antigen (PSA) are generally assumed to be indicative of tumour progression and are therefore used in clinical decision-making in men on active surveillance for early prostate cancer. OBJECTIVE: This review aims to provide support for exploiting PSA kinetics in an active surveillance setting. EVIDENCE ACQUISITION: We searched the Medline database and reviewed the evidence on both the relation between PSA kinetics before radical treatment for prostate cancer and outcome, as well as the role of PSA kinetics during active surveillance. Furthermore, the benefits and setbacks of different derivatives of PSA kinetics, minimum required time interval and number of measurements, practical recommendations, and pitfalls of their use in clinical practice are discussed. EVIDENCE SYNTHESIS: The evidence concerning the prognostic value of the PSA velocity (PSA-V) and PSA doubling time (PSA-DT) is sparse, especially in active surveillance. PSA kinetics should therefore be combined with other diagnostic measures as the trigger for deferred radical treatment or repeat prostate biopsies. There seems to be consensus among several reports on the unfavourable outcome relating to a PSA-DT <3-4 yr and on the favourable prognostic value of a PSA-DT >10 yr or a decreasing PSA level. Online tools provide help with calculations and insight on disease development. The best method of calculation, number of measurements, and time interval between measurements is unknown for now. CONCLUSIONS: Despite the current deficits in our understanding of the natural behaviour of early prostate cancer and its relation to serum PSA levels, and despite several secondary factors playing a role in PSA kinetics, PSA kinetics are a practical parameter we can offer men on active surveillance to assess the status of their disease.

The role of the digital rectal examination in subsequent screening visits in the European randomized study of screening for prostate cancer (ERSPC), Rotterdam.

BACKGROUND: The value of digital rectal examination (DRE) as a screening test for prostate cancer (PC) is controversial in the current prostate-specific antigen (PSA) era. OBJECTIVES: To determine (1) the additional value of a suspicious DRE for the detection of PC in men with an elevated PSA level in subsequent screenings and (2) the tumour characteristics of PCs detected in men with a suspicious DRE. DESIGN, SETTING, PARTICIPANTS: Within the screening study, from 1997-2006 men aged 55-75 years were invited for an every 4-yr PSA determination. A PSA level > or =3.0ng/ml prompted a DRE and a transrectal ultrasound (TRUS)-guided, lateralized sextant biopsy. Throughout the three screenings of the ERSPC, Rotterdam, 5040 biopsy sessions were evaluated. MEASUREMENTS: We determined the positive predictive values (PPVs) of a suspicious DRE and normal DRE, which entailed, respectively, the proportion of PCs detected in men with a suspicious DRE or normal DRE divided by, respectively, all biopsied men with a suspicious DRE or normal DRE. RESULTS AND LIMITATIONS: At initial screening, the PPV of a suspicious DRE, in conjunction with an elevated PSA level, to detect PC was 48.6% compared to 22.4% for men with a normal DRE. Both PPVs decreased in consecutive screens: respectively, 29.9% versus 17.1% (screen 2) and 21.2% versus 18.2% (screen 3). Respectively, 71.0% (p<0.001), 68.8% (p<0.001), and 85.7% (p=0.002) of all PCs with a Gleason score >7 were detected in men with a suspicious DRE at screens 1, 2, and 3. A limitation is that only biopsied men were evaluated. CONCLUSIONS: At initial and subsequent screenings, the chance of having cancer at biopsy was higher in men with a suspicious DRE compared to men with a normal DRE (to a lesser extent in subsequent screenings), and the combination of a PSA level > or =3.0ng/ml with a suspicious DRE resulted in detecting significantly more PCs with Gleason score >7. DRE may be useful in more selective screening procedures to decrease unnecessary biopsies and overdiagnosis.

The value of an additional hypoechoic lesion-directed biopsy core for detecting prostate cancer.

OBJECTIVE: To determine the value of a hypoechoic lesion (HL)-directed biopsy in addition to a systematic sextant biopsy for detecting prostate cancer. SUBJECTS AND METHODS: Within the European Randomized study of Screening for Prostate Cancer, 37 627 assays for prostate-specific antigen (PSA) were done in men aged 55-75 years (screening round 1-3, interval 4 years). A PSA level of >or=3.0 ng/mL prompted a systematic transrectal ultrasonography (TRUS)-guided lateralized sextant biopsy (4986 biopsy sessions were evaluated). If there was a HL, an additional lesion-directed biopsy was taken. RESULTS: At the initial screening, 1840 men were biopsied and 532 cancers were detected (28.9%). Of the men biopsied, 436 had a HL and an additional biopsy (23.7%). In these men, 230 cancers were detected (52.8%). In 3.5% (eight of 230) only the HL-directed core showed malignancy. At the repeat and third screening, respectively, 19.3% and 18.9% of the men biopsied had prostate cancer, 16.8% and 9.3% had an HL and the additional core detected two (2.2%) and one (5.9%) cancers. At the first screen most cancers found by the additional core were clinically relevant. In later screens these cancers seemed to be minimal. CONCLUSION: The performance of TRUS as a screening tool is poor. The value of the additional core was limited as only 3.5% of the visible cancers were detected solely by the additional biopsy (round 1). However, a substantial part of these cancers were clinically relevant and would have been missed without the additional biopsy. This finding was less clear in screening round 2 and 3, even in men who were not previously biopsied.

Can non-malignant biopsy features identify men at increased risk of biopsy-detectable prostate cancer at re-screening after 4 years?

OBJECTIVES: To identify pathological features in non-malignant sextant prostate needle biopsies and assess their predictive value for detecting prostate cancer on biopsy 4 years later. PATIENTS AND METHODS: We selected and reviewed the biopsy specimens of 121 men that were diagnosed as non-malignant during the first screening round of the European Randomized Study of Screening for Prostate Cancer (ERSPC), Rotterdam section. Of these 61 (50.4%) were positive for cancer during the second round (the result of a matched random sample). The biopsies were indicated by prostate-specific antigen levels of >or= 3.0 ng/mL. Specimens were scored for high-grade prostatic intraepithelial neoplasia (HGPIN), active and chronic inflammation, biopsy core length and glandular core length. The predictive value of the pathological features for detecting prostate cancer after 4 years was assessed. RESULTS: In the first-round biopsies the incidence of HGPIN was 7.1%; there was active inflammation in 22.4% and chronic inflammation in 51.0%. The mean core length was 9.3 mm and mean glandular core length 7.4 mm; the mean total biopsy length (sum of core lengths) was 56.3 mm and mean total glandular length (sum of glandular core lengths) was 44.6 mm. None of the pathological features in the initial round was significantly related to the detection of cancer in the second round. CONCLUSIONS: In this study of non-malignant prostate biopsy specimens from a screened population, no pathological features could be identified that were predictive for detecting prostate cancer on biopsy 4 years later.

Overall survival in the intervention arm of a randomized controlled screening trial for prostate cancer compared with a clinically diagnosed cohort.

OBJECTIVES: This population-based study provides comparisons of prostate cancer characteristics at diagnosis of two cohorts of men from two well-defined geographical areas exposed to different intensities of prostate cancer screening. Overall survival in both cohorts was compared with that in the general population. METHODS: A cohort of 822 men randomized to the intervention arm of a prostate cancer screening trial and subsequently diagnosed with prostate cancer was compared with a nonrandomized cohort of 947 men who were clinically diagnosed with prostate cancer in a geographically neighboring region. In both cohorts, cases were diagnosed with prostate cancer between January 1989 and December 1997. A partitioning of overall survival by variables associated with cancer onset such as age at diagnosis, stage at diagnosis, and grade at diagnosis was performed. RESULTS: Age at diagnosis, tumor extent at diagnosis, and grade at diagnosis were significantly different between the screened and clinically diagnosed cohort. The 5- and 10-yr survival rates were higher in the screened cohort than in the clinically diagnosed cohort (88.8% vs. 52.4%, and 68.4% vs. 29.6%, respectively). Significant differences in survival were evident for all age, stage, and grade subgroups, except for metastatic disease at diagnosis. CONCLUSIONS: Differences in overall survival favoring the screened population were observed for all baseline characteristics (age, stage, and grade of disease), and these variables may all explain differences in overall survival because screening achieves early diagnosis as well as a stage and grade shift. As observed survival rates in the screened population mirrored those within the general population, the contribution of lead time and overdiagnosis to final patient outcome is considered to be large as well.

Nomogram use for the prediction of indolent prostate cancer: impact on screen-detected populations.

BACKGROUND: Screening for prostate cancer has resulted in an increased incidence-to-mortality ratio. Not all cancers deserve immediate treatment. It has therefore become more important to be able to identify those cases of screen-detected prostate cancer most likely to show indolent behavior. METHODS: The Kattan-nomogram for the prediction of indolent prostate cancer was validated and recalibrated for use in a screening setting. The recalibrated nomogram was used to calculate the number of men who were predicted to have indolent cancer in a screen-detected cohort from the European Randomized study of Screening for Prostate Cancer (ERSPC), section Rotterdam. RESULTS: Of 1629 cancers detected in 2 subsequent screening rounds 825 were suitable for nomogram use. The remainder were very unlikely to have indolent cancer. A total of 485 men (485 of 825 = 59%) were predicted to have indolent cancer, which is 30% (485 of 1629) of all screen-detected cases. Cancers found at repeated screening after 4 years had a higher probability of indolent cancer than cases from the prevalence screening (44% vs 23%; P < .001). CONCLUSIONS: The current nomogram can identify substantial groups of screen-detected cancers that are likely indolent and can therefore be considered for active surveillance.

Feasibility study of adjustment for contamination and non-compliance in a prostate cancer screening trial.

BACKGROUND: The use of PSA as a screening test has become increasingly prevalent in the general population and therefore also in the control arm of the European Randomized study of Screening for Prostate Cancer (ERSPC). We present a feasibility study and impact simulation of a secondary analysis, which imitates a situation where all participants in the study are managed according to their random assignment. METHODS: The results of the Rotterdam section of the ERSPC were adjusted for contamination and non-compliance according to Cuzick et al. [Stat Med 1997; 16:1017-1029]. Endpoints of this analysis were simulated reductions in prostate cancer mortality. RESULTS: Of the men allocated to the screen arm, 27.1% were non-compliant. In the control arm 30.7% had their PSA-level measured by a general practitioner (GP) (i.e., contamination). For a scenario in which the intention-to-screen analysis was assumed to give a decrease in the mortality in the men randomized to screening of 6.7%, the secondary analysis resulted in a decrease of 16.1% for those actually screened. CONCLUSION: Although the definition of contamination as "PSA ever tested" gives an indication of the proportion of contamination, it will be important to differentiate the screening use of PSA from its diagnostic use. For the rest, adjustment for non-compliance and contamination was shown to be feasible in this prostate cancer screening trial. It can therefore be used to carry out a secondary analysis on the definitive outcome of the ERSPC and will provide accurate information for those men who are in fact screened.

Overall and disease-specific survival of patients with screen-detected prostate cancer in the European randomized study of screening for prostate cancer, section Rotterdam.

INTRODUCTION: This report describes survival data of participants of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam, diagnosed with prostate cancer (pCA) during the first round of screening, the prevalence screen. PATIENTS AND METHODS: pCA characteristics from cases diagnosed during the first screening round from December 1993 to March 2000 are shown. During follow-up, data were collected by semiannual patient chart review for the first 5 yr and annually thereafter. The causes of death are scored according to the diagnosis of the treating physician and are not based on the review of the independent causes-of-death committee. Overall and disease-specific survival graphs are shown in Kaplan-Maier projections and compared with expected survival outcomes for males in the same age categories from the Dutch provinces of North Holland and Flevoland. Statistical evaluation was based on Cox regression analysis. RESULTS: During the prevalence screening, 1014 patients were diagnosed with pCA. Median follow up was 55 mo, 126 (12.4%) patients died, 20 (2.0%) of pCA. Overall 5-yr observed and expected disease-specific survival was 97.7% and 82%, respectively. In the multivariate analysis, a Gleason sum of 4+4 or higher (p=0.025) was predictive of pCA death. CONCLUSIONS: The observed survival data are in line with the literature and the expected favorable outcome for a screened population. The proportion of men dying from pCA is still small, and a 10-yr follow-up period for the final evaluation of the ERSPC may be too short.

Should we replace the Gleason score with the amount of high-grade prostate cancer?

OBJECTIVES: The stage and grade shift of currently diagnosed prostate cancer has led to a diminished prognostic power of the Gleason score system. We investigated the predictive value of the amount of high-grade cancer (Gleason growth patterns 4/5) in the biopsy for prostate-specific antigen (PSA) and clinical relapse after radical prostatectomy. METHODS: PSA-tested participants (N=281) of the European Randomized Study of Screening for Prostate Cancer (ERSPC) who underwent radical prostatectomy were analyzed. Besides clinical features, and serum-PSA, histopathologic features as determined in the diagnostic biopsy and matching radical prostatectomy specimen were related to patient outcome. RESULTS: At a median follow-up of 7 yr, 39 (13.9%), 24 (8.5%), and 12 (4.3%) patients had PSA >/=0.1 ng/ml, PSA >/=1.0 ng/ml, and clinical relapse after radical prostatectomy, respectively. Using Cox proportional hazards, PSA level (p=0.002), length of tumour (p=0.040), and length of high-grade cancer (p=0.006) in the biopsy, but not Gleason score, were independent prognostic factors for biochemical relapse (PSA >/=0.1 ng/ml) when assessed as continuous variables. In radical prostatectomies, the proportion of high-grade cancer (p<0.001) was most predictive of relapse (PSA >/=0.1 ng/ml). For PSA >/=1.0 ng/ml and clinical relapse, the amount of high-grade cancer, both in the biopsy specimen (p=0.016 and p=0.004, respectively) and radical prostatectomy specimen (p=0.002 and p=0.005, respectively), but not Gleason score, was an independent predictor. CONCLUSIONS: In biopsy and radical prostatectomy specimens of surgically treated prostate cancer, the amount of high-grade cancer is superior to the Gleason grading system in predicting patient outcome. We propose that, in addition to the Gleason score, the amount of Gleason growth patterns 4/5 in the biopsy (whether absolute length or proportion) should be mentioned in the pathology report.

Screening for prostate cancer at low PSA range: the impact of digital rectal examination on tumor incidence and tumor characteristics.

OBJECTIVES: To compare tumor characteristics of screen-detected prostate cancers (PCs) either by digital rectal examination (DRE) or by prostate-specific antigen (PSA) as biopsy indication at low PSA. METHODS: Two populations with PSA between 2.0 and 3.9 ng/ml were studied. Group-1 was biopsied if DRE was suspicious (1st screening round, N = 1877). In group-2 all men were offered biopsy, regardless of DRE result (side-study in 2nd screening-round, N = 801). We compared cancer detection rates (CDRs) and tumor characteristics. RESULTS: In group-1 abnormal DRE prompted biopsy in 253 (13.5%) men (236 (93.3%) actually biopsied). Forty-nine PCs were detected, CDR 49/1877 = 2.6%. In group-2 we found 120 cancers in 666 (83.1%) men actually biopsied, CDR = 120/801 = 15.0%. Of all cancers detected, organ confinement (clinical T2) was found in 77.5% (group-1) and 96.6% (group-2; of which 99 T1c). Of all PCs 46.9% in group-1 and 15.0% in group-2 had biopsy Gleason score (GS) > or = 7. In the latter, 15.2% of T1cs were classified GS > or = 7. Considering only PCs with organ confinement or GS > or = 7 for each group, CDRs amounted to 2.0% versus 14.5% and 1.2% versus 2.3% for group-1 and group-2, respectively. CONCLUSIONS: PSA-based screening detected a considerable amount (15.2%) of potentially aggressive tumors as T1cs, but in addition large numbers of possibly insignificant cancers (T1c, GS = 6) were diagnosed. DRE seemed to detect more selectively high-grade cancers, but also missed many of these. Considering both populations and the need to detect aggressive but confined cancers, PSA as biopsy indication outperformed DRE at the price of more biopsies (13.5% vs. 100% if all would comply).