Risk-adjusted Screening for Prostate Cancer-Defining the Low-risk Group by Data from the PROBASE Trial.

BACKGROUND: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr. OBJECTIVE: To identify men at age 45 yr with a low risk of PCa. DESIGN, SETTING, AND PARTICIPANTS: A population-based, risk-adjusted PCa screening trial was conducted in Germany using baseline prostate-specific antigen (PSA) starting in young men (PROBASE). INTERVENTION: PSA measurements starting at the age of 45 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The incidence of PCa within 5 yr was assessed in men with screen-negative baseline PSA <1.5 ng/ml compared with those with PSA 1.5-≤3.0 ng/ml. RESULTS AND LIMITATIONS: Of 23301 men who received a first PSA test at age 45 yr, 0.79% had a screen-positive PSA value of ≥3 ng/ml. Among the 89% of men who had a screen-negative baseline PSA value of <1.5 ng/ml, only 0.45% received a positive PSA test ≥3 ng/ml upon retesting after 5 yr. By contrast, for those with a screen-negative baseline PSA value of 1.5-3 ng/ml, 13% surpassed 3 ng/ml upon biennial testing within the next 4 yr. The incidence of PCa in subsequent screening rounds increased with increasing baseline PSA levels, from 0.13 per 1000 person-years for men with initial PSA level of <1.5 ng/ml to 8.0 per 1000 person-years for those with PSA levels of 1.5-3.0 ng/ml. A limitation is a follow-up time of only 5 yr, so far. CONCLUSIONS: Men with baseline PSA <1.5 ng/ml at age 45 yr are at a very low risk of PCa over the next 5 yr. PATIENT SUMMARY: The PROBASE study showed that men with baseline prostate-specific antigen (PSA) <1.5 ng/ml at age 45 yr have a very low prostate cancer detection rate over 5 yr and do not need PSA retesting during this time.

Multiparametric Magnetic Resonance Imaging in Prostate Cancer Screening at the Age of 45 Years: Results from the First Screening Round of the PROBASE Trial.

BACKGROUND: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening. OBJECTIVE: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA). DESIGN, SETTING, AND PARTICIPANTS: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores. mpMRI scans from the first screening round for men randomised to an immediate PSA test in PROBASE were evaluated by local readers and then by two reference radiologists (experience >10 000 prostate MRI examinations) blinded to the histopathology. The PROBASE trial is registered as ISRCTN37591328 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The local and reference Prostate Imaging-Data and Reporting System (PI-RADS) scores were compared, and the sensitivity, negative predictive value (NPV), and accuracy were calculated for both readings for different cutoffs (PI-RADS 3 vs 4). RESULTS AND LIMITATIONS: Of 186 participants, 114 underwent mpMRI and FBx. PC was detected in 47 (41%), of whom 33 (29%) had clinically significant PC (csPC; International Society of Urological Pathology grade group ≥2). Interobserver reliability between local and reference PI-RADS scores was moderate (k = 0.41). At a cutoff of PI-RADS 4, reference reading showed better performance for csPC detection (sensitivity 79%, NPV 91%, accuracy of 85%) than local reading (sensitivity 55%, NPV 80%, accuracy 68%). Reference reading did not miss any PC cases for a cutoff of PI-RADS <3. If PI-RADS ≥4 were to be used as a biopsy cutoff, mpMRI would reduce negative biopsies by 68% and avoid detection of nonsignificant PC in 71% of cases. CONCLUSIONS: Prostate MRI in a young screening population is difficult to read. The MRI accuracy of for csPC detection is highly dependent on reader experience, and double reading might be advisable. More data are needed before MRI is included in PC screening for men at age 45 yr. PATIENT SUMMARY: Measurement of prostate specific antigen (PSA) is an effective screening test for early detection of prostate cancer (PC) and can reduce PC-specific deaths, but it can also lead to unnecessary biopsies and treatment. Magnetic resonance imaging (MRI) after a positive PSA test has been proposed as a way to reduce the number of biopsies, with biopsy only recommended for men with suspicious MRI findings. Our results indicate that MRI accuracy is moderate for men aged 45 years but can be increased by a second reading of the images by expert radiologists. For broad application of MRI in routine screening, double reading may be advisable.

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer.

BACKGROUND: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial. OBJECTIVE: To determine DRE diagnostic performance in a screening trial. DESIGN, SETTING, AND PARTICIPANTS: This analysis was conducted within the multicentric, randomized PROBASE trial, which enrolled >46 000 men at age 45 to test risk-adapted prostate-specific antigen (PSA) screening for PCa. INTERVENTION: (1) DRE was analyzed as a one-time, stand-alone screening offer at age 45 in 6537 men in one arm of the trial and (2) PCa detection by DRE was evaluated at the time of PSA-screen-driven biopsies (N = 578). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: (1) True-/false-positive detection rates of DRE as compared with PSA screening and (2) DRE outcome at the time of a prostate biopsy were evaluated. RESULTS AND LIMITATIONS: (1) A prospective analysis of 57 men with suspicious DRE at age 45 revealed three PCa. Detection rate by DRE was 0.05% (three of 6537) as compared with a four-fold higher rate by PSA screening (48 of 23 301, 0.21%). The true-positive detection rate by DRE relative to screening by PSA was 0.22 (95% confidence interval [CI] = [0.07-0.72]) and the false-positive detection rate by DRE was 2.2 (95% CI = [1.50-3.17]). (2) Among PSA-screen-detected PCa cases, 86% had unsuspicious DRE (sensitivity relative to PSA was 14%), with the majority of these tumors (86%) located in the potentially accessible zones of the prostate as seen by magnetic resonance imaging. CONCLUSIONS: The performance of stand-alone DRE to screen for PCa is poor. DRE should not be recommended as a PCa screening test in young men. Furthermore, DRE does not improve the detection of PSA-screen-detected PCa. PATIENT SUMMARY: Our report demonstrated the poor diagnostic performance of digital rectal examination in the screening for prostate cancer in young men.

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.5-2.99 ng/ml, 2 yearly), and high risk (>3 ng/ml, recommendation for immediate biopsy). Over the first 6 years of study participation, attendance rates to scheduled screening visits varied from 70.5% to 79.4%, depending on the study arm and risk group allocation, in addition 11.2% to 25.4% of men reported self-initiated PSA tests outside the PROBASE protocol. 38.5% of participants had a history of digital rectal examination or PSA testing prior to recruitment to PROBASE, frequently associated with family history of PCa. These men showed higher rates (33% to 57%, depending on subgroups) of self-initiated PSA testing in-between PROBASE screening rounds. In the high-risk groups (both arms), the biopsy acceptance rate was 64% overall, but was higher among men with screening PSA ≥4 ng/ml (>71%) and with PIRADS ≥3 findings upon multiparameter magnetic resonance imaging (mpMRI) (>72%), compared with men with PSA ≥3 to 4 ng/ml (57%) or PIRADS score ≤ 2 (59%). Overall, PROBASE shows good acceptance of a risk-adapted PCa screening strategy in Germany. Implementation of such a strategy should be accompanied by a well-structured communication, to explain not only the benefits but also the harms of PSA screening.

Retroperitoneal lymph node dissection in the setting of elevated markers.

PURPOSE OF REVIEW: The management of residual tumor masses in patients with metastatic germ cell tumor and persistently elevated tumor marker levels after first- and second-line chemotherapy usually excludes surgical resection. The lack of benefit of salvage chemotherapy in patients with persistently elevated markers implies a degree of chemotherapy resistance. However, previous studies demonstrated therapeutic efficacy for a surgical approach in these very particular patients. Therefore, we evaluated pre and postoperative factors, which help to identify suitable candidates, who could potentially benefit from tumor resection. RECENT FINDINGS: Preoperative parameters, which predict favorable outcomes, include good prognosis according to the International Germ Cell Cancer Collaborative group, a high preoperative level of alpha-fetoprotein in contrast to a high level of ß-HCG, stable or decreasing preoperative tumor markers and teratomatous elements in the initial testicular tumor. Retroperitoneal and mediastinal lymph nodes as target lesions are predictive for good long-term outcome due to the higher chance of complete tumor resection. Teratoma or necrosis in the resected residual tissue and postoperative marker normalization additionally represent a favorable prognosis. SUMMARY: Even in advanced chemorefractory germ cell tumor patients with elevated tumor markers the disease remains curative with radical surgery as a salvage option, if a complete resection can be achieved. Thus, a surgical approach should always be considered in the management of selected patients to avoid unnecessary salvage chemotherapy.