Operative treatment is widely used for acute proximal hamstring avulsions, but its effectiveness compared with that of nonoperative treatment has not been shown in randomized trials.
Bayesian predictive probabilities of success (PPoS) use interim trial data to calculate the probability of trial success. These quantities can be used to optimize trial size or to stop for futility. In this paper, we describe a simulation-based approach to compute the PPoS for clinical trials with competing event data, for which no specific methodology is currently available. The proposed procedure hinges on modelling the joint distribution of time to event and event type by specifying Bayesian models for the cause-specific hazards of all event types. This allows the prediction of outcome data at the conclusion of the trial. The PPoS is obtained by numerically averaging the probability of success evaluated at fixed parameter values over the posterior distribution of the parameters. Our work is motivated by two randomised clinical trials: the I-SPY COVID phase II trial for the treatment of severe COVID-19 (NCT04488081) and the STHLM3 prostate cancer diagnostic trial (ISRCTN84445406), both of which are characterised by competing event data. We present different modelling alternatives for the joint distribution of time to event and event type and show how the choice of the prior distributions can be used to assess the PPoS under different scenarios. The role of the PPoS analyses in the decision making process for these two trials is also discussed.
Since 2014, prostate cancer is reported using five-tier grouping of Gleason scores. Studies have suggested prognostic heterogeneity within the groups. We assessed the risk of prostate cancer death for men diagnosed with Gleason scores 4 + 5, 5 + 4, and 5 + 5 on needle biopsy in a population-based cohort. We used the data from Prostate Cancer data Base Sweden (PCBaSe) 4.0 for a survival analysis. Among 199 620 men reported to have prostate cancer in 2000–2020, 172 112 were diagnosed on needle biopsy. The primary treatment was classified as androgen deprivation therapy (66%), deferred treatment (5%), radical prostatectomy (7%), or radical radiotherapy (21%). The risks of death from prostate cancer in men with Gleason score 9–10 at 5 and 10 yr were used as endpoints. Multivariable Cox regression models controlling for socioeconomic factors and primary treatment were used for time-to-event analyses of death from prostate cancer and death from any causes. A total of 20 419 (12%) men had a Gleason score of 9–10, including Gleason scores of 4 + 5, 5 + 4, and 5 + 5 in 14 333 (70%), 4223 (21%), and 1863 (9%) men, respectively. The risks of prostate cancer death for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr of follow-up were 0.45 (confidence interval [CI] 0.44–0.46), 0.56 (0.55–0.58), and 0.66 (0.63–0.68), respectively. The risks of death of any cause for men with Gleason scores 4 + 5, 5 + 4, and 5 + 5 at 10 yr were 0.73 (CI 0.72–0.74), 0.81 (0.80–0.83), and 0.87 (0.85–0.89), respectively. We demonstrate in the largest and most complete cohort analyzed to date that collapsing the Gleason scores by grouping results in loss of prognostic information in men with Gleason score 9–10 cancer. Survival of prostate cancer patients with the highest tumor grades varies depending on grade composition.
Abstract A 5-tier grouping of Gleason scores has recently been proposed. Studies have indicated prognostic heterogeneity within these groups. We assessed prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) for men diagnosed with Gleason score 3 + 5 = 8, 4 + 4 = 8 and 5 + 3 = 8 acinar adenocarcinoma on needle biopsy in a population-based national cohort. The Prostate Cancer data Base Sweden 5.0 was used for survival analysis with PCSM and ACM at 5 and 10 years as endpoints. Multivariable Cox regression models controlling for socioeconomic factors, stage and primary treatment type were used for PCSM and ACM. Among 199,620 men reported with prostate cancer in 2000–2020, 172,112 were diagnosed on needle biopsy. In 18,281 (11%), there was a Gleason score of 8 in needle biopsies, including a Gleason score of 3 + 5, 4 + 4 and 5 + 3 in 11%, 86% and 2.3%, respectively. The primary treatment was androgen deprivation therapy (55%), deferred treatment (8%), radical prostatectomy (16%) or radical radiotherapy (21%). PCSM in men with Gleason scores of 3 + 5, 4 + 4 and 5 + 3 at 5 years of follow-up was 0.10 (95% CI 0.09–0.12), 0.22 (0.22–0.23) and 0.32 (0.27–0.36), respectively, and at 10 years 0.19 (0.17–0.22), 0.34 (0.33–0.35) and 0.44 (0.39–0.49), respectively. There was a significantly higher PCSM after 5 and 10 years in men with Gleason score 5 + 3 cancers than in those with 4 + 4 and in Gleason score 4 + 4 cancers than in those with 3 + 5. Grouping of Gleason scores will eliminate the prognostic granularity of Gleason scoring, thus diminishing the prognostic significance of this proposed grading system.
Background: Prostate cancer (PCa) is the leading cause of cancer death among men in Sweden. Although PSA (prostate-specific antigen) testing to screen for prostate cancer is common, its use remains controversial. This debate is primarily fueled by its insufficient operating characteristics, resulting in many benign biopsies and overdiagnosis of indolent disease. The population-based diagnostic STHLM3 trial developed and validated the Stockholm3 test, demonstrating that the combined use of PSA and Stockholm3 can identify clinically significant PCa with higher specificity while retaining the same sensitivity as PSA alone. However, the long-term implications of screening with the combined use of PSA and Stockholm3 on mortality remain unknown. Aim: This study aims to evaluate the effect of a one-time invitation for prostate cancer screening (using PSA and Stockholm3 test in combination) in men aged 50-69 living in Stockholm on prostate cancer mortality and all-cause mortality, as well as its effects on prostate cancer incidence, PSA testing, and biopsy rates. The research question investigated in this study (STHLM3-F/U) concerns one of the pre-specified secondary outcomes of the original population-based diagnostic STHLM3 study ( ISRCTN84445406 ). Randomization and Intervention: The trial involves men aged 50 to 69 living in Stockholm at the moment of invitation and who did not have a prostate cancer diagnosis. Randomization occurred at the population level using registry-based information, eligible men were randomly assigned to receive an invitation for screening or to continue with standard care. Invited men who decided to participate in the STHLM3 trial took a PSA test, followed by the Stockholm3 test if PSA level was above 1 ng/mL. Systematic biopsy was recommended for those with PSA ≥ 3 ng/mL and/or a Stockholm3 score ≥ 10%. The non-invited group did not receive any invitations and relied on standard care. Outcomes and analysis: Primary outcome was prostate cancer mortality. Secondary outcomes included all-cause mortality, prostate cancer incidence, PSA testing, and biopsy rates. Data will be analyzed using registry information, with primary analysis using follow-up data until 2023-12-31. Time to prostate cancer mortality will be analyzed using the Aalen-Johansen estimator. Cumulative risks at the end of the follow-up will be compared between the invited and non-invited groups by means of a Risk Ratio at an alpha level of 3.5%. Both intention-to-screen and compliance-adjusted analyses will be performed. Discussion: This study aims to address the knowledge gap regarding the long-term effect of screening with PSA and Stockholm3 tests in combination and provide insights into its potential effects on preventing mortality. Understanding whether a systematic organized screening intervention, using a combination of PSA and Stockholm3 has any effect on mortality can help inform decisions on prostate cancer screening policies. Ethics and dissemination: Approval for ethical conduct has been obtained from the Stockholm regional ethics committee. Results will be shared through peer-reviewed publications.
Prostate cancer grade is currently often reported both by Gleason scores and by grouping of the scores into five so-called International Society of Urological Pathology (ISUP) grades (also known as grade groups). Using population-based registry data from 172,112 men diagnosed with prostate cancer on needle biopsy, we recently investigated the outcome of Gleason score 8-10 prostate cancer with death due to prostate cancer and death from any cause as endpoints. There was a prognostic heterogeneity between Gleason scores 3+5, 4+4 and 5+3 (ISUP grade 4) and between Gleason scores 4+5, 5+4 and 5+5 (ISUP grade 5). This heterogeneity was lost when the grades collapsed into ISUP grades 4 and 5, respectively. On the other hand, there was also a prognostic overlap between these ISUP grades. The outcome of Gleason score 5+3 and 4+5 cancers was very similar. The prostate-specific mortality of Gleason scores 5+3 and 4+5 was 0.32 (95% confidence interval 0.27-0.36) and 0.30 (0.29-0.31), respectively, after 5 years and 0.44 (0.39-0.49) and 0.45 (0.44-0.46), respectively, after 10 years. The findings emphasise the importance of reporting the Gleason grades and scores for more accurate prognostic information of highly heterogeneous high-grade prostate cancers. It also questions the clinical value of the current recommendations of grouping of Gleason scores into ISUP grades or grade groups.
'/%3e%3cuse xlink:href='%23a' transform='rotate(72 0 0)'/%3e%3cuse xlink:href='%23a' transform='rotate(-72 0 0)'/%3e%3cuse xlink:href='%23a' transform='scale(-1 1) rotate(72)'/%3e%3c/g%3e%3c/defs%3e%3cpath fill='%23012169' d='M0 0h1200v600H0z'/%3e%3cpath stroke='%23FFF' stroke-width='60' d='m0 0 600 300M0 300 600 0' clip-path='url(%23b)'/%3e%3cpath stroke='%23C8102E' stroke-width='40' d='m0 0 600 300M0 300 600 0' clip-path='url(%23c)'/%3e%3cpath stroke='%23FFF' stroke-width='100' d='M300 0v300M0 150h600' clip-path='url(%23b)'/%3e%3cpath stroke='%23C8102E' stroke-width='60' d='M300 0v300M0 150h600' clip-path='url(%23b)'/%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='matrix(45.4 0 0 45.4 900 120)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='matrix(30 0 0 30 900 120)'/%3e%3cg transform='rotate(82 900 240)'%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='rotate(-82 519.022 -457.666) scale(40.4)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='rotate(-82 519.022 -457.666) scale(25)'/%3e%3c/g%3e%3cg transform='rotate(82 900 240)'%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='rotate(-82 668.57 -327.666) scale(45.4)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='rotate(-82 668.57 -327.666) scale(30)'/%3e%3c/g%3e%3cuse xlink:href='%23d' fill='%23FFF' transform='matrix(50.4 0 0 50.4 900 480)'/%3e%3cuse xlink:href='%23d' fill='%23C8102E' transform='matrix(35 0 0 35 900 480)'/%3e%3c/svg%3e)
