Stockholm3 Tests to Inform Risk Stratification before MRI and Targeted Biopsies in the Prostate Cancer Screening Setting, Journal Club - Zachary Klaassen
March 4, 2023
In this UroToday Journal Club, Zachary Klaassen discusses the publication entitled Prostate Cancer Screening Using Combination of Risk Prediction, MRI, and Targeted Prostate Biopsies, the STHLM3-MRI trial. The study performed a prospective, randomized, population-based trial among men aged 50 to 74 to evaluate various prostate cancer screening strategies. The study showed that replacing PSA with Stockholm3 tests in a setting where MRI and targeted biopsies are used decreases the number of MRIs by 36% and the number of biopsy procedures by 8%. Compared with a traditional PSA-based diagnostic workup, combining Stockholm3 with an MRI-targeted biopsy led to a 69% reduction in the rate of over-detection of prostate cancer.
Biographies:
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center
Biographies:
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Georgia Cancer Center
Read the Full Video Transcript
Christopher Wallis: Hello, and welcome to this UroToday Journal Club. Today, we are discussing a recent publication entitled, prostate cancer screening using a combination of risk prediction, MRI, and targeted prostate biopsies, the STHLM3-MRI trial. This is a prospective, population-based, randomized, open-label, non-inferiority trial. I'm Chris Wallis, an Assistant Professor in the Division of Urology at The University of Toronto. With me today is Zach Klaassen, an Assistant Professor in the Division of Urology at The Medical College of Georgia. You can see here the citation for this recent publication in Lancet Oncology.
PSA screening, as most will know, is relatively controversial. We know from population-based randomized trials, particularly those conducted in Europe, that there are benefits in terms of cancer-related morbidity and mortality. However, there are substantial harms of overdiagnosis and overtreatment, and these are associated with significant patient-related morbidity and anxiety. As a result, population-based screening using PSA testing is not currently recommended by nearly any guideline body in the world. Instead, shared decision-making is advocated. And so we have to consider the information that is available to inform shared decision making.
One of the ways to more accurately inform this process is through risk stratification. There are a number of blood-based and imaging-based tests that may be performed prior to biopsy that may reduce the number of patients both undergoing biopsy, as well as the associated morbidity and overdiagnosis of clinically indolent prostate cancer. One such blood-based test is the Stockholm3, and this has been previously validated. It includes a number of different parameters, including clinical variables, plasma proteins, and a SNP-based polygenic risk score. Stockholm3 is expressed as the risk of clinically significant prostate cancer, defined as Gleason 3+4 or greater, so this is a score between 0% and 100% or zero and one.
An alternative way of performing risk stratification is to use MRI. This may be considered in the pre-biopsy setting for risk stratification and allocation of biopsy. But it is also useful during a biopsy for targeting lesions most suspicious to harbor clinically significant disease. And so the current study seeks to assess whether the Stockholm3 risk prediction model can improve the selection of men undergoing MRI as part of a population-based program of prostate cancer screening.
To do this, they performed a prospective, randomized, population-based trial among men aged 50 to 74 years to evaluate a variety of prostate cancer screening strategies. Men were enrolled, or certainly invited, using a random male invitation among all men of eligible age in Stockholm County. Men were excluded if they had a prior prostate cancer diagnosis, had undergone prostate biopsy within 60 days, had contraindications to MRI, or had severe illness which would preclude the suitability of prostate cancer screening. Initially, patients underwent PSA testing. Those who had a PSA of less than 1.5 ng/mL were advised to repeat their PSA in six years. For those who had a higher level, Stockholm3 testers were flexibly ordered.
So this study relies on an initial paired-screen positive design with two screening tests for all participants. And so this follow-up Stockholm3 test was then evaluated using a threshold of 11%. And so those who had a PSA between 1.5-3 ng/mL and a Stockholm3 test less than 11% were advised to have repeat testing in a year. Those who had either a PSA over three or a Stockholm3 score over 11% were then carried forward.
So within this context, men were then randomized in a 2:3 ratio to standard biopsy versus the experimental biopsy approach. The experimental biopsy approach comprised an initial biparametric MRI. For those with MRI positivity, an MRI targeted as well as a systematic biopsy was performed. For those who had a negative MRI, no biopsy was performed. However, men who had a Stockholm3 score greater than 25% and a negative MRI were advised to undergo a systematic biopsy. Randomization was stratified according to sixtiles of risk according to the Stockholm3 test. All biopsies were performed by experienced urologists, and the standard TRUS biopsy using the 10-12 core approach, whereas the experimental, as we say, utilized MRI followed by biopsy among men with positive scans.
So the primary endpoint was the probability of clinically significant cancer defined as Gleason Score 3+4 or greater. Key secondary endpoints, including a probability of clinically indolent disease, the number of prostate MRIs and prostate biopsy procedures performed, as well as rates of serious adverse events among those undergoing biopsy. This was defined as death, antibiotic prescription, or hospital admission.
The study was powered to show the non-inferior sensitivity of the Stockholm3 test compared to a PSA of 3 ng/mL. They assumed that 12,500 men could be recruited with a 20% dropout rate. The true sensitivity of PSA was between 0.57 and 0.63, the relative sensitivity assumed to be one, and a non-inferiority margin of 0.78 was allowed, with an alpha of 0.025. Power is between 50% and 90%, depending on the scenario considered, with the range of true sensitivities for PSA. All analyses were performed in the intention-to-treat population.
Using the combination of a paired step and randomized design allows for a number of comparisons to be performed. So the first relevant one here is the comparison of Stockholm3 versus PSA within that experimental arm that received an MRI and targeted biopsy. The second relevant comparison is between elevated PSA and a conventional biopsy, which would be the traditional screening approach, with elevated Stockholm3 and the experimental MRI-based approach. Differences between a variety of strategies can be compared with relative sensitivities and proportions. And while the initial Stockholm3 cutoff was determined and validated to be 11%, an updated version has used a threshold of 15%. And so this was also assessed within the analysis of this study.
The discrimination of both Stockholm3 and PSA was assessed using the area under the curve or receiver operating curve, and calibration was assessed using calibration plots. A number of exploratory analyses were conducted, including a pre-specified analysis examining the biopsy data in which the systematic biopsy was omitted in order to emulate the effect of only performing MRI-targeted biopsies in those with positive MRIs. In a post hoc manner, the authors excluded biopsy data on men with negative MRIs and elevated Stockholm3 scores.
At this point in time, I am going to hand it over to Zach to walk us through the results of this trial.
Zachary Klaassen: Thanks, Chris. So as you can see, there were more than 40,000 patients were invited to participate in this study. 36,368 declined the invitation. Overall, 12,750 gave blood and were included in this study. Of those, 8,442 were excluded, the majority of which had a PSA of less than 1.5. Among the 4,308 that had a PSA greater than 1.5, 2,008 had a PSA of 1.5-3 and a Stockholm3 score of less than 11. So this left 2,300, of which 2,293 were randomly assigned. 1,372 in the experimental group and 921 in the standard group in this trial.
This looks at the baseline characteristics for the patients in this trial. On the left, you can see the variables that were assessed. To the right of that are the enrolled patients. And then the randomized patients, we will focus on the two columns on the right, which are the standard group and the experimental group. In terms of age, the age was similar between these groups, 67 years in the standard group and 66 in the experimental group. Family history of cancer, 19.1% in the standard group and 17.3 In the experimental group. PSA at the time of the study was 3.5 in each of the arms. Stockholm3 at the inclusion was 0.14 for each of the arms. And the essential equivocal prostate volume for each group at 39 CCs in the standard group and 40 CCs in the experimental group. Among patients in the experimental group that had an MRI, the majority of which were negative MRIs with the PI-RADS less than or equal to two at 59.4%, with 19% of these patients having a PI-RADS three score on their MRI.
In terms of biopsy results, you can see benign biopsy, 44% in the standard group and 11.3% in the experimental group. Moving down to clinically significant prostate cancer Gleason Score 3+4, 11.7% in the standard group, 12.3% in the experimental group. The same rate for Gleason 4+3 at 2.6% in each arm, and Gleason Score greater than or equal to 4+4, 2.7% in the standard group, and 3.1% in the experimental group.
This looks at the ROC curves for the Stockholm3 and PSA tests. On the left, you can see the Stockholm3 in red and the PSA curve in blue. The PSA AUC was 0.60 with a 95% confidence interval of 0.54-0.65. And the Stockholm3 area under the curve was 0.76 with a 95% confidence interval of 0.72-0.80. This was based on 675 men that had clinically significant prostate cancer who underwent systematic biopsies.
So these two curves are the calibration plot for the Stockholm3 test. The curve on the left shows a predicted probability of clinically significant prostate cancer from zero to one. And then the curve on the right is a zoomed-in portion of that curve with the X-axis showing a predictive probability of clinically significant prostate cancer from zero to 0.20. Taken together, the Stockholm3 test cutoff corresponding to a relative sensitivity equal to one for detection of clinically significant prostate cancer compared with a PSA greater than or equal to three was 0.15.
So the next two slides will summarize the results of this study. This table looks at the number of procedures and relative sensitivity to detect prostate cancer using the PSA or Stockholm3 test in the experimental group. So in this column here at PSA=3, you can see that there were 846 MRIs done, 338 biopsies, 105 benign biopsies, 41 Gleason 3+3, 192 Gleason 3+4, and 67 Gleason greater than or equal to 4+3. So when we move over to the next columns, this is the Stockholm3 greater than or equal to 0.11, and the one on the right is Stockholm3 greater than or equal to 0.15.
So a couple of interesting points here. We see that there were more MRIs done in the Stockholm3 greater than or equal to 0.1 compared to the PSA greater than or equal to three. We see that there were more prostate biopsies done in this group as well, 400 versus 338. And we can see that there were slightly more benign biopsies in this group, 123 versus 105. But also more clinically significant prostate cancer Gleason 3+4 in terms of Stockholm3 greater than or equal to 0.11, 227 versus 192 in the PSA group.
When we move to the far right, when we compare Stockholm3 greater than or equal to 0.15 versus PSA greater than or equal to three, we see that there were significantly fewer MRIs done, 544 versus 846, with a relative proportion of 0.64. We see that there were fewer biopsies done as well, 311 versus 338. And we see less benign biopsies. We see essentially the same Gleason 3+4, 192 in each, and the same Gleason 4+3. So essentially, in the Stockholm3 greater than or equal to 0.15, we're doing fewer MRIs, fewer biopsies, but not losing the ability to detect clinically significant prostate cancer.
This table looks at the number of men with elevated PSA or Stockholm3 tests, procedures done, and detected cancers in 10,000 men. And so on the far left here, this is elevated tests in 10,000 screened men, standard biopsies in men with PSA greater than or equal to three, 1,175, MRI targeted biopsies in men with PSA greater than or equal to 3, 1,221, MRI targeted biopsies with Stockholm3 greater than or equal to 0.11 was 1,342, and MRI targeted biopsies in men with Stockholm3 greater than or equal to 0.15 was 789.
And so a few summary points from this. If we look at the number of procedures performed, you can see there are 853 in the biopsy group compared to 1,175. 44 undergoing biopsy compared to 1,221. If we move down to the MRI, 409 for Stockholm3 greater than or equal to 0.15. So as we go through the biopsies, we see that there are fewer biopsies being done with the MRI targeted and Stockholm3 greater than or equal to 0.15. Moving to low-grade cancer, again, a trend here, so PSA greater than or equal to three, 142 low-grade cancers. As we shift our trend down to MRI targeted biopsies with Stockholm3 greater than or equal to 0.15, we are down to 45 cases detected, so less low-grade cancer for MRI targeted biopsies with a Stockholm3 score of greater than or equal to 0.15.
Lastly, we will go through clinically significant prostate cancer with standard biopsies in men with PSA greater than or equal to three, 206. As we move further down the chain, MRI targeted biopsies in men with Stockholm3 greater than or equal to 0.11, 298, and 252 for greater than or equal to 0.15. So more clinically significant prostate cancer is being detected with fewer biopsies in the MRI targeted biopsies with a Stockholm3 score greater than or equal to 0.15.
So several discussion points from this study, the STHLM3-MRI study was designed to evaluate the performance of a blood-based diagnostic test and MRI with subsequently targeted plus systematic prostate biopsies compared with traditional approaches for prostate cancer screening. And the study showed that replacing PSA with Stockholm3 tests in a setting where MRI and targeted biopsies are used decreases the number of MRIs by 36% and the number of biopsy procedures by 8%. Compared with a traditional PSA-based diagnostic workup, combining Stockholm3 with an MRI targeted biopsy approach led to a 69% reduction in the rate of over-detection of prostate cancer. Ultimately, careful selection of prediction tool cutoffs, as well as continuous surveillance of diagnostic performance, are required to achieve clinical value in this setting.
So in conclusion, the Stockholm3 tests can inform risk stratification before MRI and targeted biopsies in the prostate cancer screening setting. Diagnostic schemes, including multivariable risk prediction and an MRI-targeted biopsy approach, would substantially lower the rates of over-detection compared with traditional prostate cancer screening approaches that use PSA and systematic biopsies.
Thank you very much. We hope you enjoyed this UroToday Journal Club discussion.
Christopher Wallis: Hello, and welcome to this UroToday Journal Club. Today, we are discussing a recent publication entitled, prostate cancer screening using a combination of risk prediction, MRI, and targeted prostate biopsies, the STHLM3-MRI trial. This is a prospective, population-based, randomized, open-label, non-inferiority trial. I'm Chris Wallis, an Assistant Professor in the Division of Urology at The University of Toronto. With me today is Zach Klaassen, an Assistant Professor in the Division of Urology at The Medical College of Georgia. You can see here the citation for this recent publication in Lancet Oncology.
PSA screening, as most will know, is relatively controversial. We know from population-based randomized trials, particularly those conducted in Europe, that there are benefits in terms of cancer-related morbidity and mortality. However, there are substantial harms of overdiagnosis and overtreatment, and these are associated with significant patient-related morbidity and anxiety. As a result, population-based screening using PSA testing is not currently recommended by nearly any guideline body in the world. Instead, shared decision-making is advocated. And so we have to consider the information that is available to inform shared decision making.
One of the ways to more accurately inform this process is through risk stratification. There are a number of blood-based and imaging-based tests that may be performed prior to biopsy that may reduce the number of patients both undergoing biopsy, as well as the associated morbidity and overdiagnosis of clinically indolent prostate cancer. One such blood-based test is the Stockholm3, and this has been previously validated. It includes a number of different parameters, including clinical variables, plasma proteins, and a SNP-based polygenic risk score. Stockholm3 is expressed as the risk of clinically significant prostate cancer, defined as Gleason 3+4 or greater, so this is a score between 0% and 100% or zero and one.
An alternative way of performing risk stratification is to use MRI. This may be considered in the pre-biopsy setting for risk stratification and allocation of biopsy. But it is also useful during a biopsy for targeting lesions most suspicious to harbor clinically significant disease. And so the current study seeks to assess whether the Stockholm3 risk prediction model can improve the selection of men undergoing MRI as part of a population-based program of prostate cancer screening.
To do this, they performed a prospective, randomized, population-based trial among men aged 50 to 74 years to evaluate a variety of prostate cancer screening strategies. Men were enrolled, or certainly invited, using a random male invitation among all men of eligible age in Stockholm County. Men were excluded if they had a prior prostate cancer diagnosis, had undergone prostate biopsy within 60 days, had contraindications to MRI, or had severe illness which would preclude the suitability of prostate cancer screening. Initially, patients underwent PSA testing. Those who had a PSA of less than 1.5 ng/mL were advised to repeat their PSA in six years. For those who had a higher level, Stockholm3 testers were flexibly ordered.
So this study relies on an initial paired-screen positive design with two screening tests for all participants. And so this follow-up Stockholm3 test was then evaluated using a threshold of 11%. And so those who had a PSA between 1.5-3 ng/mL and a Stockholm3 test less than 11% were advised to have repeat testing in a year. Those who had either a PSA over three or a Stockholm3 score over 11% were then carried forward.
So within this context, men were then randomized in a 2:3 ratio to standard biopsy versus the experimental biopsy approach. The experimental biopsy approach comprised an initial biparametric MRI. For those with MRI positivity, an MRI targeted as well as a systematic biopsy was performed. For those who had a negative MRI, no biopsy was performed. However, men who had a Stockholm3 score greater than 25% and a negative MRI were advised to undergo a systematic biopsy. Randomization was stratified according to sixtiles of risk according to the Stockholm3 test. All biopsies were performed by experienced urologists, and the standard TRUS biopsy using the 10-12 core approach, whereas the experimental, as we say, utilized MRI followed by biopsy among men with positive scans.
So the primary endpoint was the probability of clinically significant cancer defined as Gleason Score 3+4 or greater. Key secondary endpoints, including a probability of clinically indolent disease, the number of prostate MRIs and prostate biopsy procedures performed, as well as rates of serious adverse events among those undergoing biopsy. This was defined as death, antibiotic prescription, or hospital admission.
The study was powered to show the non-inferior sensitivity of the Stockholm3 test compared to a PSA of 3 ng/mL. They assumed that 12,500 men could be recruited with a 20% dropout rate. The true sensitivity of PSA was between 0.57 and 0.63, the relative sensitivity assumed to be one, and a non-inferiority margin of 0.78 was allowed, with an alpha of 0.025. Power is between 50% and 90%, depending on the scenario considered, with the range of true sensitivities for PSA. All analyses were performed in the intention-to-treat population.
Using the combination of a paired step and randomized design allows for a number of comparisons to be performed. So the first relevant one here is the comparison of Stockholm3 versus PSA within that experimental arm that received an MRI and targeted biopsy. The second relevant comparison is between elevated PSA and a conventional biopsy, which would be the traditional screening approach, with elevated Stockholm3 and the experimental MRI-based approach. Differences between a variety of strategies can be compared with relative sensitivities and proportions. And while the initial Stockholm3 cutoff was determined and validated to be 11%, an updated version has used a threshold of 15%. And so this was also assessed within the analysis of this study.
The discrimination of both Stockholm3 and PSA was assessed using the area under the curve or receiver operating curve, and calibration was assessed using calibration plots. A number of exploratory analyses were conducted, including a pre-specified analysis examining the biopsy data in which the systematic biopsy was omitted in order to emulate the effect of only performing MRI-targeted biopsies in those with positive MRIs. In a post hoc manner, the authors excluded biopsy data on men with negative MRIs and elevated Stockholm3 scores.
At this point in time, I am going to hand it over to Zach to walk us through the results of this trial.
Zachary Klaassen: Thanks, Chris. So as you can see, there were more than 40,000 patients were invited to participate in this study. 36,368 declined the invitation. Overall, 12,750 gave blood and were included in this study. Of those, 8,442 were excluded, the majority of which had a PSA of less than 1.5. Among the 4,308 that had a PSA greater than 1.5, 2,008 had a PSA of 1.5-3 and a Stockholm3 score of less than 11. So this left 2,300, of which 2,293 were randomly assigned. 1,372 in the experimental group and 921 in the standard group in this trial.
This looks at the baseline characteristics for the patients in this trial. On the left, you can see the variables that were assessed. To the right of that are the enrolled patients. And then the randomized patients, we will focus on the two columns on the right, which are the standard group and the experimental group. In terms of age, the age was similar between these groups, 67 years in the standard group and 66 in the experimental group. Family history of cancer, 19.1% in the standard group and 17.3 In the experimental group. PSA at the time of the study was 3.5 in each of the arms. Stockholm3 at the inclusion was 0.14 for each of the arms. And the essential equivocal prostate volume for each group at 39 CCs in the standard group and 40 CCs in the experimental group. Among patients in the experimental group that had an MRI, the majority of which were negative MRIs with the PI-RADS less than or equal to two at 59.4%, with 19% of these patients having a PI-RADS three score on their MRI.
In terms of biopsy results, you can see benign biopsy, 44% in the standard group and 11.3% in the experimental group. Moving down to clinically significant prostate cancer Gleason Score 3+4, 11.7% in the standard group, 12.3% in the experimental group. The same rate for Gleason 4+3 at 2.6% in each arm, and Gleason Score greater than or equal to 4+4, 2.7% in the standard group, and 3.1% in the experimental group.
This looks at the ROC curves for the Stockholm3 and PSA tests. On the left, you can see the Stockholm3 in red and the PSA curve in blue. The PSA AUC was 0.60 with a 95% confidence interval of 0.54-0.65. And the Stockholm3 area under the curve was 0.76 with a 95% confidence interval of 0.72-0.80. This was based on 675 men that had clinically significant prostate cancer who underwent systematic biopsies.
So these two curves are the calibration plot for the Stockholm3 test. The curve on the left shows a predicted probability of clinically significant prostate cancer from zero to one. And then the curve on the right is a zoomed-in portion of that curve with the X-axis showing a predictive probability of clinically significant prostate cancer from zero to 0.20. Taken together, the Stockholm3 test cutoff corresponding to a relative sensitivity equal to one for detection of clinically significant prostate cancer compared with a PSA greater than or equal to three was 0.15.
So the next two slides will summarize the results of this study. This table looks at the number of procedures and relative sensitivity to detect prostate cancer using the PSA or Stockholm3 test in the experimental group. So in this column here at PSA=3, you can see that there were 846 MRIs done, 338 biopsies, 105 benign biopsies, 41 Gleason 3+3, 192 Gleason 3+4, and 67 Gleason greater than or equal to 4+3. So when we move over to the next columns, this is the Stockholm3 greater than or equal to 0.11, and the one on the right is Stockholm3 greater than or equal to 0.15.
So a couple of interesting points here. We see that there were more MRIs done in the Stockholm3 greater than or equal to 0.1 compared to the PSA greater than or equal to three. We see that there were more prostate biopsies done in this group as well, 400 versus 338. And we can see that there were slightly more benign biopsies in this group, 123 versus 105. But also more clinically significant prostate cancer Gleason 3+4 in terms of Stockholm3 greater than or equal to 0.11, 227 versus 192 in the PSA group.
When we move to the far right, when we compare Stockholm3 greater than or equal to 0.15 versus PSA greater than or equal to three, we see that there were significantly fewer MRIs done, 544 versus 846, with a relative proportion of 0.64. We see that there were fewer biopsies done as well, 311 versus 338. And we see less benign biopsies. We see essentially the same Gleason 3+4, 192 in each, and the same Gleason 4+3. So essentially, in the Stockholm3 greater than or equal to 0.15, we're doing fewer MRIs, fewer biopsies, but not losing the ability to detect clinically significant prostate cancer.
This table looks at the number of men with elevated PSA or Stockholm3 tests, procedures done, and detected cancers in 10,000 men. And so on the far left here, this is elevated tests in 10,000 screened men, standard biopsies in men with PSA greater than or equal to three, 1,175, MRI targeted biopsies in men with PSA greater than or equal to 3, 1,221, MRI targeted biopsies with Stockholm3 greater than or equal to 0.11 was 1,342, and MRI targeted biopsies in men with Stockholm3 greater than or equal to 0.15 was 789.
And so a few summary points from this. If we look at the number of procedures performed, you can see there are 853 in the biopsy group compared to 1,175. 44 undergoing biopsy compared to 1,221. If we move down to the MRI, 409 for Stockholm3 greater than or equal to 0.15. So as we go through the biopsies, we see that there are fewer biopsies being done with the MRI targeted and Stockholm3 greater than or equal to 0.15. Moving to low-grade cancer, again, a trend here, so PSA greater than or equal to three, 142 low-grade cancers. As we shift our trend down to MRI targeted biopsies with Stockholm3 greater than or equal to 0.15, we are down to 45 cases detected, so less low-grade cancer for MRI targeted biopsies with a Stockholm3 score of greater than or equal to 0.15.
Lastly, we will go through clinically significant prostate cancer with standard biopsies in men with PSA greater than or equal to three, 206. As we move further down the chain, MRI targeted biopsies in men with Stockholm3 greater than or equal to 0.11, 298, and 252 for greater than or equal to 0.15. So more clinically significant prostate cancer is being detected with fewer biopsies in the MRI targeted biopsies with a Stockholm3 score greater than or equal to 0.15.
So several discussion points from this study, the STHLM3-MRI study was designed to evaluate the performance of a blood-based diagnostic test and MRI with subsequently targeted plus systematic prostate biopsies compared with traditional approaches for prostate cancer screening. And the study showed that replacing PSA with Stockholm3 tests in a setting where MRI and targeted biopsies are used decreases the number of MRIs by 36% and the number of biopsy procedures by 8%. Compared with a traditional PSA-based diagnostic workup, combining Stockholm3 with an MRI targeted biopsy approach led to a 69% reduction in the rate of over-detection of prostate cancer. Ultimately, careful selection of prediction tool cutoffs, as well as continuous surveillance of diagnostic performance, are required to achieve clinical value in this setting.
So in conclusion, the Stockholm3 tests can inform risk stratification before MRI and targeted biopsies in the prostate cancer screening setting. Diagnostic schemes, including multivariable risk prediction and an MRI-targeted biopsy approach, would substantially lower the rates of over-detection compared with traditional prostate cancer screening approaches that use PSA and systematic biopsies.
Thank you very much. We hope you enjoyed this UroToday Journal Club discussion.