Grade groups (GGs) are an important parameter for therapeutic decision making in prostate cancer (Pca) patients. Invasive cribriform and/or intraductal carcinoma (CR/IDC) has an independent ...prognostic value for disease outcome, but are not included in the GG limiting their clinical use.
To perform a proof-of-principle study incorporating CR/IDC in the current GG.
All prostate biopsies of 1031 men with screen-detected Pca between 1993 and 2000 were reviewed for the current GG (ranging from 1 to 5) and CR/IDC. The cribriform grade (cGrade) was equal to the GG if CR/IDC was present and GG minus 1 if not. GG1 was cGrade1 if intraductal carcinoma was absent.
Biopsy review for GG and CR/IDC. A total of 406 patients had received radical prostatectomy (RP), 508 radiotherapy (RT), 108 surveillance, and eight hormonal therapy, and the treatment was unknown for one patient.
Outcome measurements and statistical analysis disease-specific survival (DSS), metastasis-free survival (MFS), and biochemical recurrence–free survival (BCRFS) after 15.1 yr (interquartile range 10.9–19.7 yr) follow-up were compared using Harrell’s C-statistic.
The biopsy GGs were 486 GG1, 310 GG2, 104 GG3, 64 GG4, and 67 GG5; cGrade distributions were 738 cGrade1, 102 cGrade2, 91 cGrade3, 58 cGrade4, and 42 cGrade5. The cGrade had a better discriminative value than the GG for DSS (C-index 0.79; 95% confidence interval 0.74–0.83 vs 0.76; 0.71–0.82) and MFS (0.79; 0.74–0.84 vs 0.77; 0.72–0.82). The discriminative value for BCRFS after RP and RT was similar for both models. Different diagnostic, such as use of sextant biopsies, and therapeutic strategies in the 1990s are the limitations of this study.
The cGrade is a simple Pca grade modification with better discriminative values for DSS and MFS than the GG, particularly impacting decision making in men with current GG2 Pca.
Microscopic grading is an important factor for decision making in prostate cancer (Pca) patients. We show that a simple grade modification better predicts Pca outcome and might improve treatment choices.
Pathological grading is an important parameter for decision making in prostate cancer patients. We show that a simple modification of the current International Society of Urologic Pathology/World Health Organization grade groups incorporating cribriform architecture results in a significantly better discriminative value for disease-specific and metastasis-free survival.
Purpose
To evaluate the health-related quality of life (HRQoL) of Japanese men on active surveillance (AS) in the Prostate cancer Research International Active Surveillance study in Japan ...(PRIAS-JAPAN).
Methods
Participants were included in the PRIAS-JAPAN HRQoL study between January 2010 and March 2016. Their general HRQoL was assessed using a validated Japanese version of the Short-Form 8 Health Survey (SF-8) at enrolment and annually thereafter until discontinuation of AS. The SF-8 mental component summary (MCS) and physical component summary (PCS) of men on AS were compared with scores of the general population (norm-based score NBS: 50) and MCS and PCS scores for men following AS were analysed over time. We tested whether MCS and PCS scores over time explained discontinuation of AS.
Results
Five hundred and twenty-five patients enrolled, and the median age at baseline was 68 years. At enrolment and after 1-, 2-, and 3-year follow-ups, the PCS and MCS scores were significantly higher than the NBS of the general Japanese population except for the median PCS at 3 years. We found that age at diagnosis and time on AS negatively affected the PCS score of men on AS, while every additional year on AS led to a 0.27 point increase in MCS scores. Neither PCS nor MCS were predictors for discontinuation of AS.
Conclusion
Japanese men following an AS strategy for 3 years reported better HRQoL compared with the general population, indicating that monitoring Japanese low-risk prostate cancer patients can be an effective treatment strategy.
Study registration
Clinical trial registry—UMIN (University Hospital Medical Information Network); UMIN000002874 (2009/12/11)
Background
The diagnosis of (significant) prostate cancer ((s)PC) is impeded by overdiagnosis and unnecessary biopsy. Risk calculators (RC) have been developed to mitigate these issues. Contemporary ...RCs integrate clinical characteristics with mpMRI findings.
Objective
To validate two of these models—the MRI-ERSPC-RC-3/4 and the risk model of van Leeuwen.
Methods
265 men with clinical suspicion of PC were enrolled. Every patient received a prebiopsy mpMRI, which was reported according to PI-RADS v2.1, followed by MRI/TRUS fusion-biopsy. Cancers with ISUP grade ≥ 2 were classified as sPC.
Outcome measurements and statistical analysis
Statistical analysis was performed by comparing discrimination, calibration, and clinical utility
Results
There was no significant difference in discrimination between the RCs. The MRI-ERSPC-RC-3/4-RC showed a nearly ideal calibration-slope (0.94; 95% CI 0.68–1.20) than the van Leeuwen model (0.70; 95% CI 0.52–0.88). Within a threshold range up to 9% for a sPC, the MRI-ERSPC-RC-3/4-RC shows a greater net benefit than the van Leeuwen model. From 10 to 15%, the van Leeuwen model showed a higher net benefit compared to the MRI-ERSP-3/4-RC. For a risk threshold of 15%, the van Leeuwen model would avoid 24% vs. 14% compared to the MRI-ERSPC-RC-3/4 model; 6% vs. 5% sPC would be overlooked, respectively.
Conclusion
Both risk models supply accurate results and reduce the number of biopsies and basically no sPC were overlooked. The van Leeuwen model suggests a better balance between unnecessary biopsies and overlooked sPC at thresholds range of 10–15%. The MRI-ERSPC-RC-3/4 risk model provides better overall calibration.
Individual growth patterns and cribriform architecture are increasingly considered in risk stratification and clinical decision-making in men with prostate cancer. Our objective was to establish the ...prognostic value of individual Gleason 5 patterns in a radical prostatectomy (RP) cohort. We reviewed 1064 RPs and recorded Grade Group (GG), pT-stage, surgical margin status, Gleason 4 and 5 growth patterns as well as intraductal carcinoma. The clinical endpoints were biochemical recurrence and post-operative distant metastasis. Gleason pattern 5 was present in 339 (31.9%) RPs, of which 47 (4.4%) presented as primary, 166 (15.6%) as secondary, and 126 (11.8%) as tertiary pattern. Single cells/cords were present in 321 (94.7%) tumors with Gleason pattern 5, solid fields in 90 (26.5%), and comedonecrosis in invasive carcinoma in 32 (9.4%) tumors. Solid fields demonstrated either a small nested morphology (n = 50, 14.7%) or medium to large solid fields (n = 61, 18.0%). Cribriform architecture was present in 568 (53.4%) RPs. Medium to large solid fields and comedonecrosis coincided with cribriform architecture in all specimens, and were not observed in cribriform-negative cases. In multivariable analysis adjusted for Prostate-Specific Antigen, pT-stage, GG, surgical margin status and lymph node metastases, cribriform architecture (Hazard Ratio (HR) 9.9; 95% Confidence Interval (CI) 3.9–25.5, P < 0.001) and comedonecrosis (HR 2.1, 95% CI 1.2–3.7, P = 0.01) were independent predictors for metastasis-free survival, while single cells/cords (HR 1.2; 95% CI 0.7–1.8, P = 0.55) and medium to large solid fields (HR 1.6, 95% CI 0.9–2.7, P = 0.09) were not. In conclusion, comedonecrosis in invasive carcinoma is an independent prognostic Gleason 5 pattern for metastasis-free survival after RP. These data support the current recommendations to routinely include cribriform pattern in pathology reports and indicate that comedonecrosis should also be commented on.
It remains crucial to reduce unnecessary testing and overdiagnosis of prostate cancer. However, it is clear that early detection of prostate cancer can reduce suffering and death from the disease.
...The ERSPC study has demonstrated that prostate-specific antigen (PSA)-based screening results in a relative increase in diagnosis of (low-risk) prostate cancer (PCa) and a reduction in metastatic disease and PCa mortality.
To evaluate the burden of PCa among men randomized to active screening compared to those in the control arm in ERSPC Rotterdam.
We analyzed data for participants in the Dutch section of the ERSPC, including 21 169 men randomized to the screening arm and 21 136 randomized to the control arm. Men in the screening arm were invited for PSA-based screening every 4 yr, and transrectal ultrasound–guided prostate biopsy was recommended for those with PSA ≥3.0 ng/ml.
We analyzed detailed follow-up and mortality data up to January 1, 2019, to a maximum of 21 yr, using multistate models.
At 21 yr, 3046 men (14%) had been diagnosed with nonmetastatic PCa and 161 (0.76%) with metastatic PCa in the screening arm. In the control arm, 1698 men (8.0%) had been diagnosed with nonmetastatic PCa and 346 (1.6%) with metastatic PCa. In comparison to the control arm, men in the screening arm were diagnosed with PCa almost 1 yr earlier and if diagnosed with nonmetastatic PCa lived on average for almost 1 yr longer without disease progression. Among those who experienced biochemical recurrence (18–19% after nonmetastatic PCa), progression to metastatic disease or death was quicker in the control arm: men in the screening arm lived for 7.17 yr without progression, while the progression-free interval was only 1.59 yr for men in the control arm over a 10-yr time period. Among those who experienced metastatic disease, men in both study arms lived for 5 yr over a 10-yr time period.
PCa diagnosis was earlier after study entry for men in the PSA-based screening arm. However, disease progression was not as fast in the screening arm as in the control arm: once men in the control arm experienced biochemical recurrence, progression to metastatic disease or death was 5.6 yr faster than in the screening arm. Our results confirm the ability of early disease detection to reduce suffering and death from PCa at the cost of earlier (and more frequent) treatment-induced reductions in quality of life.
Our study shows that early detection of prostate cancer can reduce suffering and death from this disease. However, screening based on measurement of prostate-specific antigen (PSA) can also result in an earlier treatment-induced reduction in quality of life.
Risk stratification can be used to reduce the numbers of systematic prostate biopsy procedures, magnetic resonance imaging scans, and targeted prostate biopsies, but clinicians should be aware of the ...a priori risk of their patient cohort to realize the full benefit of this powerful approach.
Risk stratification in the diagnostic pathway of prostate cancer (PCa) can be used to reduce biopsies and magnetic resonance imaging (MRI) scans, while maintaining the detection of clinically significant PCa (csPCa). The use of highly discriminating and well-calibrated models will generate better clinical outcomes if context-dependent thresholds are used.
To retrospectively assess the effect of the upfront use of the Rotterdam Prostate Cancer Risk Calculator (RPCRC) developed in a screening cohort and the RPCRC-MRI developed in a clinical cohort while exploring the need to adapt thresholds in biopsy-naïve men in the PRECISION (Prostate Evaluation for Clinically Important Disease: Sampling Using Image Guidance or Not?) trial.
In the transrectal ultrasonography arm, we evaluated 188 men; in the MRI arm, we evaluated 206 (for the reduction of MRI scans) and 137 (for the reduction of targeted biopsies) men.
Performance was assessed by discrimination, calibration, and clinical utility.
The performance of the RPCRC was good. However, intercept adjustment was warranted. Net benefit was observed from a recalibrated probability of 32% for any PCa and 10% for csPCa. After recalibration and applying a threshold of 20% for any PCa or 10% for csPCa, 28% of all biopsies could have been reduced, missing five cases of csPCa. The uncalibrated RPCRC could reduce 35% of all MRI scans, with a threshold of 20% for any PCa or 4% for csPCa. In the MRI arm, performance was good without stressing recalibration. Net benefit was observed from a probability of 22% for any PCa and 7% for csPCa. With a threshold of 20% for any PCa or 4% for csPCa, 9% of all targeted biopsies could be reduced, missing one grade group 2 PCa.
The performance of the RPCRC and RPCRC-MRI in men included in the PRECISION trial was good, but recalibration and adaptation of the risk threshold of the RPCRC are indicated to reach optimal performance.
In this report, we show that risk stratification with the Rotterdam Prostate Cancer Risk Calculator has added value in reducing harm, but adjustment to reflect the characteristics of the patient cohort is indicated.
Pre-clinical studies have suggested sex hormone signalling pathways may influence tumorigenesis in neuroendocrine neoplasia (NEN). We conducted a retrospective, population-based study to compare ...overall survival (OS) between males and females with NEN. A total of 14,834 cases of NEN diagnosed between 2012 and 2018, recorded in England's National Cancer Registry and Analysis Service (NCRAS), were analysed. The primary outcome was OS with 5 years maximum follow-up. Multivariable analysis, restricted mean survival time and mediation analysis were performed. Appendiceal, pulmonary and early-stage NEN were most commonly diagnosed in females; stomach, pancreatic, small intestinal, colonic, rectal and later-stage NEN were more often diagnosed in males. Females displayed increased survival irrespective of the stage, morphology or level of deprivation. On average, they survived 3.62 (95% CI 1.73-5.90) to 10.26 (6.6-14.45) months longer than males; this was statistically significant in NEN of the lung, pancreas, rectum and stomach (
< 0.001). The stage mediated improved survival in stomach, lung, and pancreatic NEN but not in rectal NEN. The reasons underlying these differences are not yet understood. Overall, females diagnosed with NEN tend to survive longer than males, and the stage at presentation only partially explains this. Future research, as well as prognostication and treatment, should consider sex as an important factor.
Objectives
To recalibrate and validate the European Randomized Study of Screening for Prostate Cancer risk calculators (ERSPC RCs) 3/4 and the magnetic resonance imaging (MRI)‐ERSPC‐RCs to a ...contemporary Norwegian setting to reduce upfront prostate multiparametric MRI (mpMRI) and prostate biopsies.
Patients and Methods
We retrospectively identified and entered all men who underwent prostate mpMRI and subsequent prostate biopsy between January 2016 and March 2017 in a Norwegian centre into a database. mpMRI was reported using PI‐RADS v2.0 and clinically significant prostate cancer (csPCa) defined as Gleason ≥ 3 + 4. Probabilities of csPCa and any prostate cancer (PCa) on biopsy were calculated by the ERSPC RCs 3/4 and the MRI‐ERSPC‐RC and compared with biopsy results. RCs were then recalibrated to account for differences in prevalence between the development and current cohorts (if indicated), and calibration, discrimination and clinical usefulness assessed.
Results
Three hundred and three patients were included. The MRI‐ERSPC‐RCs were perfectly calibrated to our cohort, although the ERSPC RCs 3/4 needed recalibration. Area under the receiver operating curve (AUC) for the ERSPC RCs 3/4 was 0.82 for the discrimination of csPCa and 0.77 for any PCa. The AUC for the MRI‐ERSPC‐RCs was 0.89 for csPCa and 0.85 for any PCa. Decision curve analysis showed clear net benefit for both the ERSPC RCs 3/4 (>2% risk of csPCa threshold to biopsy) and for the MRI‐ERSPC‐RCs (>1% risk of csPCa threshold), with a greater net benefit for the MRI‐RCs. Using a >10% risk of csPCa or 20% risk of any PCa threshold for the ERSPC RCs 3/4, 15.5% of mpMRIs could be omitted, missing 0.8% of csPCa. Using the MRI‐ERSPC‐RCs, 23.4% of biopsies could be omitted with the same threshold, missing 0.8% of csPCa.
Conclusion
The ERSPC RCs 3/4 and MRI‐ERSPC‐RCs can considerably reduce both upfront mpMRI and prostate biopsies with little risk of missing csPCa.
Background:
Urinary incontinence is a prevalent form of pelvic floor dysfunction, with a non-negligible impact on a patient’s quality of life. There are several treatment options, varying from ...conservative to invasive. The aim of this study is to predict treatment outcomes of pure or predominant urge urinary incontinence (UUI) in women to support shared decision-making and manage patient expectations.
Methods:
Data on patient characteristics, disease history, and investigations of 512 consecutive women treated for UUI in three hospitals in the Netherlands were retrospectively collected. The predicted outcome was the short-term subjective continence outcome, defined as patient-reported continence 3 months after treatment categorized as cure (no urinary leakage), improvement (any degree of improvement of urinary leakage), and failure (no improvement or worsening of urinary leakage). Multivariable ordinal regression with backward stepwise selection was performed to analyze association between outcome and patient’s characteristics. Interactions between patient characteristics and treatment were added to estimate individual treatment benefit. Discriminative ability was assessed with the ordinal c-statistic.
Results:
Conservative treatment was applied in 12% of the patients, pharmacological in 62%, and invasive in 26%. Subjective continence outcome was cure, improvement, and failure in 20%, 49%, and 31%, respectively. Number of incontinence episodes per day, voiding frequency during the day, subjective quantity of UI, coexistence of stress urinary incontinence (SUI), night incontinence, and bladder capacity and the interactions between these variables were included in the model. After internal validation, the ordinal c-statistic was 0.699.
Conclusions:
Six variables were of value to predict pure or predominant UUI treatment outcome in women. Further development into a comprehensive set of models for the use in various pelvic floor disorders and treatments is recommended to optimize individualized care. This model requires external validation before implementation in clinical practice.
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