Prostate cancer risk assessment by the primary care physician and urologist: transabdominal- versus transrectal ultrasound prostate volume-based use of the Rotterdam Prostate Cancer Risk Calculator.

Background: Our objective was to assess the accuracy of transabdominal ultrasound (TAUS) measured prostate volume in the primary care setting with transrectal ultrasound (TRUS) measured prostate volume by the urologist as the reference test. Furthermore, our objective was to assess whether risk-stratification using TAUS prostate volume by the primary care physician could reduce unnecessary referrals to the urologist. Methods: Men in two Dutch primary care offices with a prostate cancer (PCa) screening request received a digital rectal examination (DRE), prostate specific-antigen (PSA), and TAUS prostate volume measurement by the general practitioner, followed by Rotterdam Prostate Cancer Risk Calculator (RPCRC) risk assessment. The examination was repeated by a urologist using TRUS. A prostate biopsy was performed in case of a RPCRC positive biopsy advice. A non-inferiority analysis was performed comparing TAUS and TRUS prostate volume differences. A risk-based referral strategy using TAUS and the RPCRC in the primary care setting was compared with the standard referral strategy based on PSA (≥3 ng/mL) and DRE. Results: A total of 105 men were included with a median PSA of 1.9 ng/mL. The mean prostate volumes measured by TAUS and TRUS were 55 and 45 mL, respectively. The mean overestimation of the prostate volume by TAUS as compared to the reference test was 9.9 mL (95% CI: 5.9-13.8). According to Dutch standard practice, 41 out of 105 (39%) men would have been referred to the urologist. Stratification in primary care based on the RPCRC using TAUS prostate volume would have avoided 29 out of the 41 (71%) referrals, at the expense of non-referral of 5 out of 11 (45%) men with a biopsy indication, according to the urologist. Conclusions: RPCRC-based risk stratification in primary care using TAUS prostate volume measurement is feasible and may prevent unnecessary referrals to the urologist and reduce costs. The accuracy of the risk assessment with TAUS might be improved by sufficient training and centralization to achieve a higher volume of consultations in primary care facilities.

Shifting risk-stratified early prostate cancer detection to a primary healthcare setting.

OBJECTIVE: To evaluate the feasibility of multivariable risk stratification for early prostate cancer (PCa) detection in a primary healthcare diagnostic facility with regard to its effects on the referral rate and subsequent PCa diagnoses compared to a PSA threshold of 3.0 ng/mL as the current referral indicator. PATIENTS AND METHODS: In 2014, the Erasmus MC Cancer Institute and the primary healthcare diagnostic facility STAR-SHL (located in Rotterdam city centre) initiated this observational study, in which general practitioners (GPs) could refer men who wished to undergo PCa screening to STAR-SHL for consultation by specially trained personnel. Referral recommendations to secondary healthcare were based on the outcome of application of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) and were compared to the current Dutch GPs' PSA referral threshold of 3.0 ng/mL. For data collection on PCa diagnoses, the study cohort was linked to the Dutch nationwide pathology databank (PALGA). RESULTS: Between January 2014 and February 2021, 507 men were referred for consultation and in 495 men prostate-specific antigen (PSA) was tested. The median (interquartile range) follow-up from consultation to PALGA linkage was 43 (25-65) months. In total, 279 men (56%) had a PSA level ≥3.0 ng/mL, of whom 68% (95% confidence interval [95% CI] 63-74) were considered at low risk according to the RPCRC. Within 1 year after consultation, one of these men (0.52%; 95% CI 0.092-2.9) was diagnosed with clinically significant (cs)PCa (i.e., International Society of Urological Pathology Grade Group ≥2). Thereafter, another four (2.1%; 95% CI 0.82-5.3) low-risk men were diagnosed with csPCa. Of the high-risk men who were biopsied within 1 year after consultation (n = 61), 77% (95% CI 65-86) were diagnosed with PCa and 49% (95% CI 37-61) with csPCa. CONCLUSION: In a primary healthcare diagnostic facility, the RPCRC could reduce up to 68% of referrals to secondary healthcare, as compared to a PSA referral threshold of 3.0 ng/mL. Deploying the RPCRC in this setting resulted in a high csPCa detection rate in those men biopsied. This strategy can be considered safe since the observational data showed low proportions of csPCa among men at low risk.

Biomarker-Oriented Therapy in Bladder and Renal Cancer.

Treatment of patients with urothelial carcinoma (UC) of the bladder or renal cancer has changed significantly during recent years and efforts towards biomarker-directed therapy are being investigated. Immune checkpoint inhibition (ICI) or fibroblast growth factor receptor (FGFR) directed therapy are being evaluated for non-muscle invasive bladder cancer (NMIBC) patients, as well as muscle-invasive bladder cancer (MIBC) patients. Meanwhile, efforts to predict tumor response to neoadjuvant chemotherapy (NAC) are still ongoing, and genomic biomarkers are being evaluated in prospective clinical trials. Currently, patients with metastatic UC (mUC) are usually treated with second-line ICI, while cisplatin-ineligible patients with programmed death-ligand 1 (PD-L1) positive tumors can benefit from first-line ICI. Platinum-relapsed UC patients harboring FGFR2/3 mutations can be treated with erdafitinib, while enfortumab vedotin has emerged as a novel third-line treatment option for mUC. In metastatic (clear cell) renal cell carcinoma (RCC), ICI was first introduced as second-line treatment after vascular endothelial growth factor receptor-tyrosine kinase inhibition (VEGFR-TKI). Currently, ICIs have also been introduced as first-line treatment in metastatic RCC. Although there is no evidence up to now for beneficial adjuvant treatment after surgery with VEGFR-TKIs in high-risk non-metastatic RCC, several trials are underway investigating the potential beneficial effect of ICIs in this setting.

Distribution of Prostate Imaging Reporting and Data System score and diagnostic accuracy of magnetic resonance imaging-targeted biopsy: comparison of an Asian and European cohort.

BACKGROUND: This study aimed to compare the distribution of Prostate Imaging Reporting and Data System (PI-RADS) score and the diagnostic accuracy of magnetic resonance imaging (MRI)-targeted biopsy and systematic biopsy between a Chinese and a Dutch cohort. MATERIALS AND METHODS: Our study includes 316 men from Shanghai Changhai Hospital, China, and 266 men from the Erasmus University Medical Center, Rotterdam, the Netherlands. All men had a suspicion for prostate cancer (PCa) and were offered an multiparametric MRI (mpMRI) scan. RESULTS: The distribution of the PI-RADS score was different between the two cohorts (P = 0.008). In the Chinese cohort of PI-RADS ≥3, the detection rate for high-grade PCa (Gleason ≥7) was 37.3% by systematic biopsy and 35.5% by MRI-targeted biopsy. The sensitivity of systematic biopsy was 0.80 for PCa and 0.75 for high-grade PCa. MRI-targeted biopsy achieved slightly higher sensitivity for PCa (0.82) and high-grade PCa (0.76). In the Dutch cohort of PI-RADS ≥3, the high-grade PCa detection rate was 44.4% and 54.5% for systematic biopsy and MRI-targeted biopsy. The sensitivity of systematic biopsy was 0.93 for PCa and 0.81 for high-grade PCa. By MRI-targeted biopsy, the sensitivity was 0.85 for PCa and 0.97 for high-grade PCa. CONCLUSIONS: The distribution of the PI-RADS score was different with more PI-RADS 4/5 in the Chinese cohort. Applying a PI-RADS ≥3 cutoff resulted in a favorable overall sensitivity. MRI-targeted biopsy showed a higher sensitivity in the detection of high-grade PCa than systematic biopsy. The sensitivity of MRI-targeted biopsy and systematic biopsy for both PCa and high-grade PCa in the Dutch cohort was superior to those in the Chinese cohort.

Prediction of High-grade Prostate Cancer Following Multiparametric Magnetic Resonance Imaging: Improving the Rotterdam European Randomized Study of Screening for Prostate Cancer Risk Calculators.

BACKGROUND: The Rotterdam European Randomized Study of Screening for Prostate Cancer risk calculators (ERSPC-RCs) help to avoid unnecessary transrectal ultrasound-guided systematic biopsies (TRUS-Bx). Multivariable risk stratification could also avoid unnecessary biopsies following multiparametric magnetic resonance imaging (mpMRI). OBJECTIVE: To construct MRI-ERSPC-RCs for the prediction of any- and high-grade (Gleason score ≥3 + 4) prostate cancer (PCa) in 12-core TRUS-Bx±MRI-targeted biopsy (MRI-TBx) by adding Prostate Imaging Reporting and Data System (PI-RADS) and age as parameters to the ERSPC-RC3 (biopsy-naïve men) and ERSPC-RC4 (previously biopsied men). DESIGN, SETTING, AND PARTICIPANTS: A total of 961 men received mpMRI and 12-core TRUS-Bx±MRI-TBx (in case of PI-RADS ≥3) in five institutions. Data of 504 biopsy-naïve and 457 previously biopsied men were used to adjust the ERSPC-RC3 and ERSPC-RC4. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Logistic regression models were constructed. The areas under the curve (AUCs) of the original ERSPC-RCs and MRI-ERSPC-RCs (including PI-RADS and age) for any- and high-grade PCa were compared. Decision curve analysis was performed to assess the clinical utility of the MRI-ERSPC-RCs. RESULTS AND LIMITATIONS: MRI-ERSPC-RC3 had a significantly higher AUC for high-grade PCa compared with the ERSPC-RC3: 0.84 (95% confidence interval [CI] 0.81-0.88) versus 0.76 (95% CI 0.71-0.80, p<0.01). Similarly, MRI-ERSPC-RC4 had a higher AUC for high-grade PCa compared with the ERSPC-RC4: 0.85 (95% CI 0.81-0.89) versus 0.74 (95% CI 0.69-0.79, p<0.01). Unlike for the MRI-ERSPC-RC3, decision curve analysis showed clear net benefit of the MRI-ERSPC-RC4 at a high-grade PCa risk threshold of ≥5%. Using a ≥10% high-grade PCa risk threshold to biopsy for the MRI-ERSPC-RC4, 36% biopsies are saved, missing low- and high-grade PCa, respectively, in 15% and 4% of men who are not biopsied. CONCLUSIONS: We adjusted the ERSPC-RCs for the prediction of any- and high-grade PCa in 12-core TRUS-Bx±MRI-TBx. Although the ability of the MRI-ERSPC-RC3 for biopsy-naïve men to avoid biopsies remains questionable, application of the MRI-ERSPC-RC4 in previously biopsied men in our cohort would have avoided 36% of biopsies, missing high-grade PCa in 4% of men who would not have received a biopsy. PATIENT SUMMARY: We have constructed magnetic resonance imaging-based Rotterdam European Randomized study of Screening for Prostate Cancer (MRI-ERSPC) risk calculators for prostate cancer prediction in transrectal ultrasound-guided biopsy and MRI-targeted biopsy by incorporating age and Prostate Imaging Reporting and Data System score into the original ERSPC risk calculators. The MRI-ERSPC risk calculator for previously biopsied men could be used to avoid one-third of biopsies following MRI.

Multivariable risk-based patient selection for prostate biopsy in a primary health care setting: referral rate and biopsy results from a urology outpatient clinic.

BACKGROUND: According to their guidelines, Dutch general practitioners (GPs) refer men with prostate-specific antigen (PSA) level ≥3.0 ng/mL to the urologist for risk-based patient selection for prostate biopsy using the Rotterdam Prostate Cancer Risk Calculator (RPCRC). Use of the RPCRC in primary care could optimize the diagnostic pathway even further by reducing unnecessary referrals. To investigate this, we calculated the risk and assessed the rate of men referred to the urologist with PSA level ≥3.0 ng/mL by implementing the RPCRC in a primary health care setting. METHODS: In January 2014, an exploratory study was initiated in collaboration with the primary health care facility of the GP laboratory in Rotterdam. GPs were given the possibility to refer men with a suspicion of prostate cancer (PCa) or a screening wish to this primary care facility (STAR-SHL) where further assessment was performed by specially trained personnel. Risk-based advice on referral to the urologist was given to the GP on the basis of the RPCRC results. If requested, advice on the treatment of lower urinary tract symptoms (LUTS) was provided. All men signed informed consent. RESULTS: Between January 2014 and September 2017, a total of 243 men, median age 64 [interquartile range (IQR), 57-70] years were referred for a consultation at the primary care facility. Of the 108 men with PSA level ≥3.0 ng/mL and a referral related to PCa, GPs were advised to refer 58 men to the urologist (54%). Of the men with available follow-up (FU) data [n=187, median FU, 16 (IQR, 9-25) months] 54 men were considered high-risk (i.e., had an elevated risk of PCa as calculated by the RPCRC). Of these men, 51 (94%) were actually referred to secondary care by their GP, and so far 38 men underwent biopsy. PCa was detected in 30 men [47% had Gleason score (GS) ≥3+4 PCa], translating to an overall positive predictive value (PPV) of 79%. Within the available FU time, 2 out of 38 (5%) men with PSA level ≥3.0 ng/mL which were considered low-risk have been diagnosed with GS 3+3 PCa. CONCLUSIONS: Risk-stratification with the RPCRC in a primary health care setting could prevent almost half of referrals of men with PSA level ≥3.0 ng/mL to the urologist. In more than three-quarters of men referred for prostate biopsy, the suspicion of PCa was confirmed and almost half of men had clinically significant PCa (GS ≥3+4 PCa). These data show a huge potential for multivariable risk-stratification in primary care.

Characteristics of Prostate Cancer Found at Fifth Screening in the European Randomized Study of Screening for Prostate Cancer Rotterdam: Can We Selectively Detect High-grade Prostate Cancer with Upfront Multivariable Risk Stratification and Magnetic Resonance Imaging?

BACKGROUND: The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio. OBJECTIVE: To assess the potential of a risk-based strategy including MRI to selectively identify men aged ≥70 yr with high-grade PCa. DESIGN, SETTING, AND PARTICIPANTS: Three hundred and thirty-seven men with prostate-specific antigen ≥3.0 ng/ml at a fifth screening (71-75 yr) in the European Randomized study of Screening for Prostate Cancer Rotterdam were biopsied. One hundred and seventy-nine men received six-core transrectal ultrasound biopsy (TRUS-Bx), while 158 men received MRI, 12-core TRUS-Bx, and fusion TBx in case of Prostate Imaging Reporting and Data System ≥3 lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the overall, low-grade (Gleason Score 3+3) and high-grade (Gleason Score ≥ 3+4) PCa rate. Secondary outcome was the low- and high-grade PCa rate detected by six-core TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx. Tertiary outcome was the reduction of biopsies and low-grade PCa detection by upfront risk stratification with the Rotterdam Prostate Cancer Risk Calculator 4. RESULTS AND LIMITATIONS: Fifty-five percent of men were previously biopsied. The overall, low-grade, and high-grade PCa rates in biopsy naïve men were 48%, 27%, and 22%, respectively. In previously biopsied men these PCa rates were 25%, 20%, and 5%. Sextant TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx had a similar high-grade PCa rate (11%, 12%, and 11%) but a significantly different low-grade PCa rate (17%, 28%, and 7%). Rotterdam Prostate Cancer Risk Calculator 4-based stratification combined with 12-core TRUS-Bx ± MRI-TBx would have avoided 65% of biopsies and 68% of low-grade PCa while detecting an equal percentage of high-grade PCa (83%) compared with a TRUS-Bx all men approach (79%). CONCLUSIONS: After four repeated screens and ≥1 previous biopsies in half of men, a significant proportion of men aged ≥70 yr still harbor high-grade PCa. Upfront risk stratification and the combination of MRI and TRUS-Bx would have avoided two-thirds of biopsies and low-grade PCa diagnoses in our cohort, while maintaining the high-grade PCa detection of a TRUS-Bx all men approach. Further studies are needed to verify these results. PATIENT SUMMARY: Prostate cancer screening reduces mortality but is accompanied by unnecessary biopsies and overdiagnosis of nonaggressive tumors, especially in repeatedly screened elderly men. To tackle these drawbacks screening should consist of an upfront risk-assessment followed by magnetic resonance imaging and transrectal ultrasound-guided biopsy.

Additional benefit of using a risk-based selection for prostate biopsy: an analysis of biopsy complications in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer.

OBJECTIVE: To investigate biopsy complications and hospital admissions that could be reduced by the use of European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators. MATERIALS AND METHODS: All biopsies performed in the Rotterdam section of the ERSPC between 1993 and 2015 were included. Biopsy complications and hospital admission data were prospectively recorded in questionnaires that were completed 2 weeks after biopsy. The ERSPC risk calculators 3 (RC3) and 4 (RC4) were applied to men attending the first and subsequent rounds of screening, respectively. Applying the predefined RC3/4 probability thresholds for prostate cancer (PCa) risk of ≥12.5% and high-grade PCa risk ≥3%, we assessed the number of complications, admissions and costs that could be reduced by avoiding biopsies in men below these thresholds. RESULTS: A total of 10 747 biopsies with complete questionnaires were included. For these biopsies a complication rate of 67.9% (7294/10 747), a post-biopsy fever rate of 3.9% (424/10747) and a hospital admission rate of 0.9% (92/10747) were recorded. The fever rate was found to be static over the years, but the hospital admission rate tripled from 0.6% (1993-1996) to 2.1% (2009-2015). Among 7704 biopsies which fit the criteria for RC3 or RC4, 35.8% of biopsies (2757/7704), 37.4% of complications (1972/5268), 39.4% of fever events (128/325) and 42.3% of admissions (30/71) could have been avoided by using one of the risk calculators. More complications could have been avoided if RC4 had been used and for more recent biopsies (2009-2015). Our findings show that 35.9% of the total cost of biopsies and complication treatment could have been avoided. CONCLUSION: A significant proportion of biopsy complications, hospital admissions and costs could be reduced if biopsy decisions were based on ERSPC risk calculators instead of PSA only. This effect was most prominent in more recent biopsies and in men with repeated biopsies or screening.

Risk-stratification based on magnetic resonance imaging and prostate-specific antigen density may reduce unnecessary follow-up biopsy procedures in men on active surveillance for low-risk prostate cancer.

OBJECTIVES: To assess the value of risk-stratification based on magnetic resonance imaging (MRI) and prostate-specific antigen density (PSA-D) in reducing unnecessary biopsies without missing Gleason pattern 4 prostate cancer in men on active surveillance (AS). PATIENTS AND METHODS: In all, 210 men on AS with Gleason score 3 + 3 prostate cancer received a first MRI and if indicated [Prostate Imaging Reporting and Data System (PI-RADS) score ≥3] targeted biopsy (TBx) using MRI-transrectal ultrasonography (TRUS) fusion. The MRI was performed 3 months after diagnosis (group A: n = 97), at confirmatory biopsy (group B: n = 39) or at surveillance biopsy after one or more repeat TRUS-guided systematic biopsies (TRUS-Bx) (group C: n = 74). The primary outcome was upgrading to Gleason score ≥3 + 4 prostate cancer based on MRI ± TBx in groups A, B and C. Biopsy outcomes were stratified for the overall PI-RADS score and PSA-D to identify a subgroup of men in whom a biopsy could have been avoided as no Gleason score upgrading was detected. RESULTS: In all, 134/210 (64%) men had a positive MRI and 51/210 (24%) men had Gleason score upgrading based on MRI-TBx. The percentage of Gleason score upgrading based on MRI-TBx was 23% (22/97), 23% (9/39) and 27% (20/74) in respectively groups A, B and C. Additional Gleason score upgrading detected by TRUS-Bx occurred in 8% (3/39) of men in group B and 6% (1/17) of men who received TRUS-Bx in group C. No Gleason score upgrading was detected by MRI-TBx in men with a PI-RADS score of 3 and a PSA-D of <0.15 ng/mL2 (n = 15), nor by TRUS-Bx in men with a PI-RADS score of 1-3 and a PSA-D of <0.15 ng/mL2 (n = 15). CONCLUSION: At least one out of five men on AS with Gleason score 3 + 3 prostate cancer at diagnostic TRUS-Bx show Gleason score upgrading based on first MRI ± TBx at baseline, confirmatory or surveillance biopsy. Men with a PI-RADS score of 1-3 and PSA-D of <0.15 ng/mL2 did not show Gleason score upgrading at MRI ± TBx or TRUS-Bx at each time point of surveillance. Thus risk-stratification based on PI-RADS and PSA-D may reduce unnecessary follow-up biopsy procedures in men on AS.

Biopsy undergrading in men with Gleason score 6 and fatal prostate cancer in the European Randomized study of Screening for Prostate Cancer Rotterdam.

OBJECTIVES: A total of 15 men who died of prostate cancer had cT1/2 biopsy Gleason score ≤6 prostate cancer at prevalence screening in the European Randomized study of Screening for Prostate Cancer Rotterdam. Our objective was to explain (part of) these prostate cancer deaths by undergrading with the classical Gleason score. METHODS: Biopsy specimens of 98 men with classical Gleason score ≤6 or 3 + 4 = 7 at prevalence screening in the European Randomized study of Screening for Prostate Cancer Rotterdam were retrospectively reviewed by two pathologists using the International Society of Urological Pathology 2014 modified Gleason score. These 98 men included 15 men with cT1/2 classical Gleason score ≤6 who died of prostate cancer (cases) and 83 randomly selected men with classical Gleason score ≤6 or 3 + 4 = 7 (controls). The primary outcome was the reclassification rate from classical Gleason score ≤6 to modified classical Gleason score 3 + 4 = 7 (grade group 2) stratified for prostate cancer death. The secondary outcome was the rate of cribriform/intraductal carcinoma in Gleason score-reclassified men stratified for prostate cancer death. RESULTS: A total of 79 out of 98 men had classical Gleason score ≤6 prostate cancer. A total of eight out of 15 (53%) prostate cancer deaths with classical Gleason score ≤6 were reclassified to modified Gleason score 3 + 4 = 7, compared with 16 out of 64 (25%) men with non-fatal prostate cancer (P = 0.017). A total of five out of eight (63%) Gleason score-reclassified men with fatal prostate cancer had cribriform/intraductal carcinoma, compared with two out of 16 (13%) Gleason score-reclassified men with non-fatal prostate cancer (P = 0.011). CONCLUSIONS: Part of the prostate cancer deaths with Gleason score ≤6 at prevalence screening in the European Randomized study of Screening for Prostate Cancer Rotterdam could be explained by biopsy undergrading. The present study confirms that the International Society of Urological Pathology 2014 modified Gleason score is more accurate for prognostic assessment based on prostate biopsy than the classical Gleason score.

Complications after prostate biopsies in men on active surveillance and its effects on receiving further biopsies in the Prostate cancer Research International: Active Surveillance (PRIAS) study.

OBJECTIVE: To study the risk of serial prostate biopsies on complications in men on active surveillance (AS) and determine the effect of complications on receiving further biopsies. PATIENTS AND METHODS: In the global Prostate cancer Research International: Active Surveillance (PRIAS) study, men are prospectively followed on AS and repeat prostate biopsies are scheduled at 1, 4, and 7 years after the diagnostic biopsy, or once yearly if prostate-specific antigen-doubling time is <10 years. Data on complications after biopsy, including infection, haematuria, haematospermia, and pain, were retrospectively collected for all biopsies taken during follow-up in men from several large participating centres. Generalised estimating equations were used to test predictors of infection after biopsy. Competing risk analysis was used to compare the rates of men receiving further biopsies between men with and without previous complications. RESULTS: In all, 2 184 biopsies were taken in 1 164 men. Infection was reported after 55 biopsies (2.5%), and one in five men reported any form of complication. At multivariable analysis, the number of previous biopsies was not a significant predictor of infection (odds ratio 1.04, 95% confidence interval 0.76-1.43). The only significant predictor for infection was the type of prophylaxis used. Of all men with a complication at the diagnostic or first repeat biopsy, 21% did not have a repeat biopsy at the time a repeat biopsy was scheduled according to protocol, vs 12% for men without a previous biopsy complication. CONCLUSION: In our present cohort of men on AS, we found no evidence that repeat prostate biopsy in itself posed a risk of infection. However, complications after biopsy were not uncommon and after a complication men were less likely to have further biopsies. We should aim to safely reduce the amount of repeat biopsies in men on AS.

Risk-based Patient Selection for Magnetic Resonance Imaging-targeted Prostate Biopsy after Negative Transrectal Ultrasound-guided Random Biopsy Avoids Unnecessary Magnetic Resonance Imaging Scans.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) is increasingly used in men with suspicion of prostate cancer (PCa) after negative transrectal ultrasound (TRUS)-guided random biopsy. Risk-based patient selection for mpMRI could help to avoid unnecessary mpMRIs. OBJECTIVE: To study the rate of potentially avoided mpMRIs after negative TRUS-guided random biopsy by risk-based patient selection using the Rotterdam Prostate Cancer Risk Calculator (RPCRC). DESIGN, SETTING, AND PARTICIPANTS: One hundred and twenty two consecutive men received a mpMRI scan and subsequent MRI-TRUS fusion targeted biopsy in case of suspicious lesion(s) (Prostate Imaging Reporting and Data System ≥ 3) after negative TRUS-guided random biopsy. Men were retrospectively stratified according to the RPCRC biopsy advice to compare targeted biopsy outcomes after risk-based patient selection with standard (prostate specific antigen and/or digital rectal examination-driven) patient selection. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The rate of potentially avoided mpMRIs by RPCRC-based patient selection in relation to the rate of missed high-grade (Gleason ≥ 3+4) PCa. Receiver operating characteristic curve analysis was performed to determine the area under the curve of the RPCRC for (high-grade) PCa. RESULTS AND LIMITATIONS: Of the 60 men with a positive biopsy advice, six (10%) had low-grade PCa and 28 (47%) had high-grade PCa in targeted biopsy. Of the 62 men with a negative advice, two (3%) had low-grade PCa and three (5%) had high-grade PCa. Upfront RPCRC-based patient selection would have avoided 62 (51%) of 122 mpMRIs and two (25%) of eight low-grade PCa diagnoses, missing three (10%) of 31 high-grade PCa. The area under the curve of the RPCRC for PCa and high-grade PCa was respectively 0.76 (95% confidence interval 0.67-0.85) and 0.84 (95% confidence interval 0.76-0.93). CONCLUSIONS: Risk-based patient selection with the RPCRC can avoid half of mpMRIs after a negative prostate specific antigen and/or digital rectal examination-driven TRUS-guided random biopsy. Further improvement in risk-based patient selection for mpMRI could be made by adjusting the RPCRC for MRI-targeted biopsy outcome prediction. PATIENT SUMMARY: The suspicion of prostate cancer remains in many men after a negative ultrasound-guided prostate biopsy. These men increasingly receive an often unnecessary magnetic resonance imaging (MRI) scan. We found that patient selection for MRI based on the Rotterdam Prostate Cancer Risk Calculator biopsy advice could avoid half of the MRIs.

Targeted therapies in bladder cancer: an overview of in vivo research.

Survival of patients with muscle-invasive bladder cancer is poor and new therapies are needed. Currently, none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer and the few clinical trials that have been performed had limited success, often owing to a lack of efficacy and toxic effects. However, many other novel targeted agents have been investigated in animal models of bladder cancer. EGFR, FGFR-3, VEGF, mTOR, STAT3, the androgen receptor and CD24 are molecular targets that could be efficiently inhibited, resulting in reduced tumour growth, and that have been investigated in multiple independent studies. Several other targets, for example COX-2, IL-12, Bcl-xL, livin and choline kinase α, have also been observed to inhibit tumour growth, but these findings have not been replicated to date. Limitations of several studies include the use of cell lines with mutations downstream of the target, providing resistance to the tested therapy. Furthermore, certain technologies, such as interfering RNAs, although effective in vitro, are not yet ready for clinical applications. Further preclinical research is needed to discover and evaluate other possible targets, but several validated targets are now available to be studied in clinical trials.

Compliance Rates with the Prostate Cancer Research International Active Surveillance (PRIAS) Protocol and Disease Reclassification in Noncompliers.

BACKGROUND: Men with prostate cancer on active surveillance (AS) are advised to follow strict follow-up schedules and switch to definitive treatment on risk reclassification. However, some men might not adhere to these strict protocols. OBJECTIVE: To determine the number of noncompliers and disease reclassification rates in men not complying with the follow-up protocol of the Prostate Cancer Research International Active Surveillance (PRIAS) study. DESIGN, SETTING, AND PARTICIPANTS: A total of 4547 men with low-risk prostate cancer were included and prospectively followed on AS. Men were regularly examined using prostate-specific antigen (PSA), digital rectal examination, and repeat biopsies, and were advised to switch to definitive treatment on disease reclassification (>cT2c, Gleason score > 3+3, >2 cores positive, or PSA doubling time [PSA-DT] 0-3 yr). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Rates of men not complying with follow-up visits or a recommendation to discontinue AS are reported. Biopsy outcome (Gleason ≥7 or >2 cores positive) was compared between compliers and noncompliers using Cox proportional hazards analysis. RESULTS AND LIMITATIONS: The compliance rate for PSA visits was 91%. By contrast, the compliance rate for standard repeat biopsies decreased over time (81%, 60%, 53%, and 33% at 1, 4, 7, and 10 yr after diagnosis, respectively). Yearly repeat biopsies in men with faster rising PSA (PSA-DT 3-10 yr) was low at <30%, although these men had higher upgrading rates at repeat biopsy (25-30% vs 16%). PSA-DT of 0-3 yr was the most common recommendation for discontinuation, but 71% continued on AS. Men with PSA-DT of 0-3 yr were at higher risk of upgrading on repeat biopsy (hazard ratio 2.02, 95% confidence interval 1.36-3.00) compared to men without fast rising PSA. CONCLUSION: Some men and their physicians do not comply with AS follow-up protocols. In particular, yearly repeat biopsies in men with fast rising PSA are often ignored, as is the recommendation to discontinue AS because of very fast rising PSA. Although these men are at greater risk of higher Gleason scores on repeat biopsy, the majority still exhibit favorable tumor characteristics. Fast rising PSA should therefore not trigger a recommendation to receive active treatment, but should rather serve as a criterion for stricter follow-up. In addition, we should aim to find ways of safely reducing the number of biopsies to increase adherence to AS protocols. PATIENT SUMMARY: We looked at compliance with an active surveillance protocol for low-risk prostate cancer in a large active surveillance study. We observed reluctance to undergo yearly biopsies because of fast rising prostate-specific antigen, despite a higher risk of disease progression. Further research should aim to safely reduce the number of repeat biopsies in men on active surveillance to increase protocol adherence.

[Guidelines on the early detection of prostate cancer]. / Richtlijnen voor vroegdiagnostiek van prostaatkanker.

The early diagnosis of prostate cancer presents certain dilemmas, and various prostate cancer guidelines have been developed to support clinicians in decision making. However, these guidelines often give contradictory advice and should be appraised critically. We will discuss how the general practitioner (GP) should deal with the frequently used, often contradictory guidelines on this topic. A number of dilemmas concerning the early diagnosis of prostate cancer are discussed in this clinical lesson, based on a single case in the GP's practice; this concerns a 49-year-old male who approached his GP for prostate cancer screening. After the process of shared decision making, the patient was screened and diagnosed with a low-grade prostate carcinoma for which active surveillance was initiated.

Prostate-specific antigen-based prostate cancer screening: Past and future.

Prostate-specific antigen-based prostate cancer screening remains a controversial topic. Up to now, there is worldwide consensus on the statement that the harms of population-based screening, mainly as a result of overdiagnosis (the detection of clinically insignificant tumors that would have never caused any symptoms), outweigh the benefits. However, worldwide opportunistic screening takes place on a wide scale. The European Randomized Study of Screening for Prostate Cancer showed a reduction in prostate cancer mortality through prostate-specific antigen based-screening. These population-based data need to be individualized in order to avoid screening in those who cannot benefit and start screening in those who will. For now, lacking a more optimal screening approach, screening should only be started after the process of shared decision-making. The focus of future research is the reduction of unnecessary testing and overdiagnosis by further research to better biomarkers and the value of the multiparametric magnetic resonance imaging, potentially combined in already existing prostate-specific antigen-based multivariate risk prediction models.