Cribriform pattern 4/intraductal carcinoma of the prostate and persistent prostate‐specific antigen after radical prostatectomy
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ABSTRACT:
SUBMITTER: Sasaki T
PROVIDER: S-EPMC11250726 | biostudies-literature | 2024 May
REPOSITORIES: biostudies-literature
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Project description:ImportanceWhether the conventional 1.5-month to 2.0-month time interval following radical prostatectomy (RP) for prostate cancer (PC) is sufficient to accurately document a persistent prostate-specific antigen (PSA) remains unanswered.ObjectiveTo evaluate the time necessary to accurately document a persistent PSA level after RP.Design, setting, and participantsThis cohort study evaluated whether a significant interaction existed between (1) a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less and (2) persistent PSA vs undetectable PSA after RP on PC-specific mortality (PCSM) risk and all-cause mortality (ACM) risk, adjusting for known PC prognostic factors, age at RP, year of RP, and the time-dependent use of post-RP radiation therapy (RT) and androgen deprivation therapy (ADT). Whether an increasing persistent PSA level was associated with a worse prognosis was also investigated. Patients with T1N0M0 to T3N0M0 PC treated with RP between 1992 and 2020 at 2 academic centers were included. Follow-up data were collected until November 2023. Data were analyzed from July 2024 to January 2025.ExposureRP.Main outcomes and measuresAdjusted hazard ratio (aHR) of ACM and PCSM risk.ResultsOf 30 461 patients included in the discovery cohort, the median (IQR) age was 64 (59-68) years; of 12 837 patients included in the validation cohort, the median (IQR) age was 59 (54-64) years. Compared with patients with undetectable PSA, among patients with persistent PSA, a pre-RP PSA level greater than 20 ng/mL vs 20 ng/mL or less was significantly associated with reduced ACM risk (aHR, 0.69; 95% CI, 0.51-0.91; P = .01; P for interaction < .001) and PCSM risk (aHR, 0.41; 95% CI, 0.25-0.66; P < .001; P for interaction = .02). This result remained after adjustment for prostate volume and was confirmed in the validation cohort for PCSM risk and may represent a higher proportion of patients with a pre-RP PSA greater than 20 ng/mL vs 20 ng/mL or less who could have reached an undetectable PSA level if additional time for PSA assessment occurred before initiating post-RP therapy for presumed persistent PSA. Notably, there was more frequent and a shorter median time to post-RP RT plus ADT or ADT use in patients with a pre-RP PSA greater than 20 ng/mL (244 of 446 [54.7%] at a median [IQR] of 2.68 [1.51-4.40] months) vs 20 ng/mL or less (338 of 972 [34.8%] at a median [IQR] of 3.30 [2.00-5.39] months). These treatment times were shorter than the times to an undetectable PSA in observed patients (median [IQR] of 2.96 [1.84-3.29] months vs 3.37 [2.35-4.09] months, respectively). Increasing persistent PSA level was associated with an increased ACM risk (aHR, 1.14; 95% CI, 1.04-1.24; P = .004) and PCSM risk (aHR, 1.27; 95% CI, 1.12-1.45; P < .001).Conclusions and relevancePSA level assessed for at least 3 months after RP may minimize overtreatment, and in this study, a higher persistent PSA level was associated with a worse prognosis.
| S-EPMC11907358 | biostudies-literature
Project description:The aim of the present study was to explore DNA methylation aberrations in association with cribriform architecture and intraductal carcinoma (IDC) of the prostate, as there is robust evidence that these morphological features are associated with aggressive disease and have significant clinical implications. Herein, the associations of a panel of seven known prognostic DNA methylation biomarkers with cribriform and IDC features were examined in a series of 91 Gleason pattern (GP) 4 tumors derived from Gleason score 7 radical prostatectomies. Gene specific DNA methylation was compared between cribriform and/or IDC positive vs. negative cases, and in association with clinicopathological features, using Chi square and Mann-Whitney U tests. DNA methylation of the adenomatous polyposis coli, Ras association domain family member 1 and T-box 15 genes was significantly elevated in GP4 tumors with cribriform and/or IDC features compared with negative cases (P=0.045, P=0.007 and P=0.013, respectively). To the best of our knowledge, this provides the first evidence for an association between cribriform and/or IDC and methylation biomarkers, and warrants further investigation of additional DNA methylation events in association with various architectural patterns in prostate cancer.
| S-EPMC5494878 | biostudies-literature
Project description:ObjectiveTo investigate the association of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) with clinicopathological features and long-term oncological prognosis for the development of a potential management strategy.MethodsA systematic literature search was performed using PubMed and Web of Science up to June 2021 to identify the eligible studies focusing on understanding the impact of persistent PSA in patients who underwent RP for localized prostate cancer. Meta-analyses were performed on parameters with available information.ResultsA total of 32 RP studies were identified, of which 11 included 26 719 patients with consecutive cohorts and the remaining 21 comprised 24 177 patients with cohorts carrying specific restrictions. Of the 11 studies with consecutive cohorts, the incidence of persistent PSA varied between 3.1% and 34.6% with a median of 11.0%. Meta-analyses revealed patients with persistent PSA consistently showed unfavorable clinicopathological features and a more than 3.5-fold risk of poorer biochemical recurrence, metastasis, and prostate cancer-specific mortality prognosis independently, when compared to patients with undetectable PSA. Similarly, cases with persistent PSA in different specific patient cohorts with a higher risk of prostate cancer also showed a trend of worse outcomes.ConclusionWe found that the frequency of persistent PSA was about 11.0% in consecutive RP cohorts. Persistent PSA was significantly associated with unfavorable clinicopathological characteristics and worse oncological outcomes. Patients with persistent PSA after RP may benefit from early salvage treatment to delay or prevent biochemical recurrence, improving oncological outcomes for these patients. Further prospective randomized controlled trials are warranted to understand optimal systemic therapy in these patients.
| S-EPMC10394292 | biostudies-literature
Project description:The hypersensitive prostate specific antigen (PSA) test can measure in 0.01 ng/mL units, and its efficacy for screening after radical prostatectomy (RP) has been reported. In this study, we assessed patients who underwent RP to evaluate whether the nadir value affects biochemical recurrence (BCR). From 1995 to 2014, patients classified as N0 who had negative resection margins and a nadir PSA of less than 0.2 ng/mL were evaluated. The characteristics, pathological outcomes, PSA after RP, and BCR were assessed. A total of 1483 patients were enrolled. Among them, 323 (21.78%) patients showed BCR after RP. The mean age of the BCR group was 63.86±7.31 years, and while that of the no-recurrence group was 64.06±6.82 years (P = 0.645). The mean preoperative PSA of the BCR group was 9.75±6.92 ng/mL and that of the no-recurrence group was 6.71±5.19 ng/mL (P < 0.001). The mean time to nadir (TTN) in the BCR group was 4.64±7.65 months, while that in the no-recurrence group was 7.43±12.46 months (P < 0.001). The mean PSA nadir value was 0.035±0.034 ng/mL in the BCR group and 0.014±0.009 ng/mL in the no-recurrence group (P < 0.001). In multivariable Cox regression analyses, Gleason score, positive biopsy core percentages, minimal invasive surgery, nadir PSA value, and TTN were independently associated with BCR. The mean BCR occurred at 48.23±2.01 months after RP, and there was a significant difference in BCR occurrence according to the nadir PSA value (P < 0.001). A high PSA nadir value and short TTN may predict the risk of BCR after successful RP, aiding the identification of candidates for adjuvant or salvage therapies after RP.
| S-EPMC8092790 | biostudies-literature
Project description:PurposeThe risk of biochemical recurrence is inversely related to the relapse-free interval after radical prostatectomy. We examined predictors of late biochemical recurrence, and the relationship between timing of biochemical recurrence and long-term survival outcomes.Materials and methodsOf 10,609 men treated with radical prostatectomy 1,684 had biochemical recurrence. We examined predictors of late biochemical recurrence (more than 10 years after radical prostatectomy), and calculated metastasis-free and cancer specific survival rates from the time of biochemical recurrence. In the subset of 1,583 men with an undetectable prostate specific antigen at 10 years we calculated actuarial metastasis-free and cancer specific survival estimates at 20 years after radical prostatectomy.ResultsOf the biochemical recurrence studied 77.0%, 16.6%, 4.9% and 1.5% occurred at 5 or less, greater than 5 to 10, greater than 10 to 15 and more than 15 years postoperatively. Late recurrence was associated with more favorable pathological features, as well as higher metastasis-free and cancer specific survival rates. For men with an undetectable prostate specific antigen at 10 years the actuarial probability of biochemical recurrence and metastasis at 20 years varied by stage and grade, with no metastases in patients with a prostatectomy Gleason score 6 or less. A single patient with an undetectable prostate specific antigen at 10 years died of prostate cancer within 20 years after radical prostatectomy.ConclusionsMen with an undetectable prostate specific antigen for more than 10 years have a low risk of subsequent biochemical recurrence, with correspondingly lower rates of metastasis and death. These patients should be counseled that their risk of subsequent cancer related morbidity and mortality is low. Furthermore, these results suggest that annual prostate specific antigen testing may be safely discontinued after 10 years for men with a prostatectomy Gleason score 6 or less and/or limited life expectancy.
| S-EPMC4750470 | biostudies-literature
Project description:The present study aimed to assess the association between the cribriform pattern (CP)/intraductal carcinoma (IDC) and the adverse pathological and clinical outcomes in the radical prostatectomy (RP) cohort. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA). The protocol from this review was registered on the PROSPERO platform. We searched PubMed®, the Cochrane Library and EM-BASE® up to the 30th of April 2022. The outcomes of interest were the extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LNS met), risk of biochemical recurrence (BCR), distant metastasis (MET) and disease-specific death (DSD). As a result, we identified 16 studies with 164 296 patients. A total of 13 studies containing 3254 RP patients were eligible for the meta-analysis. The CP/IDC was associated with adverse outcomes, including EPE (pooled OR = 2.55, 95%CI 1.23-5.26), SVI (pooled OR = 4.27, 95%CI 1.90-9.64), LNs met (pooled OR = 6.47, 95%CI 3.76-11.14), BCR (pooled OR = 5.09, 95%CI 2.23-11.62) and MET/DSD (pooled OR = 9.84, 95%CI 2.75-35.20, p < 0.001). In conclusion, the CP/IDC belong to highly malignant prostate cancer patterns which have a negative impact on both the pathological and clinical outcomes. The presence of the CP/IDC should be included in the surgical planning and postoperative treatment guidance.
| S-EPMC10000112 | biostudies-literature
Project description:We performed a systematic review and meta-analysis to assess the prognostic value of prostate-specific antigen (PSA) persistence 4-8 weeks after radical prostatectomy (RP) in patients with prostate cancer, using studies from Medline, Scopus, and Cochrane Library, on 10 October 2020. Studies were eligible if they compared patients with postoperative PSA persistence 4-8 weeks after RP to those without such persistence to assess the value of PSA persistence in prognosticating biochemical recurrence (BCR), disease recurrence, cancer-specific mortality (CSM), and overall mortality (OM) by multivariable analysis. Our review and analysis included nine studies published between 2008 and 2019 with 14,455 patients. Of those studies, 12.0% showed postoperative PSA persistence. PSA persistence was associated with BCR (HR: 4.44, 95% CI: 2.84-6.93), disease recurrence (HR: 3.43, 95% CI: 1.62-7.25), and CSM (HR: 2.32, 95% CI: 1.83-2.95). We omitted meta-analysis on the association of PSA persistence with OM due to an insufficient number of studies. PSA persistence was associated with disease recurrence in a sub-group of patients with pathological nodal involvement (HR: 5.90, 95% CI: 3.76-9.24). Understanding detection of PSA persistence at 4-8 weeks after RP might be useful for patient counseling, follow-up scheduling, and clinical decision-making regarding adjuvant therapies.
| S-EPMC7956516 | biostudies-literature
Project description: Not available
| S-EPMC7658155 | biostudies-literature
Project description:Ultrasensitive prostate-specific antigen (u-PSA) remains controversial for follow-up after radical prostatectomy (RP). The aim of this study was to model PSA doubling times (PSADT) for predicting biochemical recurrence (BCR) and to capture possible discrepancies between u-PSA and traditional PSA (t-PSA) by utilizing advanced statistical modeling. 555 RP patients without neoadjuvant/adjuvant androgen deprivation from the Turku University Hospital were included in the study. BCR was defined as two consecutive PSA values >0.2 ng/mL and the PSA measurements were log2-transformed. One third of the data was reserved for independent validation. Models were first fitted to the post-surgery PSA measurements using cross-validation. Major trends were then captured using linear mixed-effect models and a predictive generalized linear model effectively identified early trends connected to BCR. The model generalized for BCR prediction to the validation set with ROC-AUC of 83.6% and 95.1% for the 1 and 3 year follow-up censoring, respectively. A web-based tool was developed to facilitate its use. Longitudinal trends of u-PSA did not display major discrepancies from those of t-PSA. The results support that u-PSA provides useful information for predicting BCR after RP. This can be beneficial to avoid unnecessary adjuvant treatments or to start them earlier for selected patients.
| S-EPMC5090356 | biostudies-literature
Project description:ObjectivesTo assess the correlation of pathological radical prostatectomy (RP) specimen features and prostate-specific antigen (PSA) characteristics to imaging findings on subsequent 18 F-DCFPyL positron emission tomography/computed tomography (PET/CT) in patients with biochemical failure (BF).Patients and methodsRetrospective analysis of combined 18 F-DCFPyL PET/CT database of patients from centres in Australia and New Zealand was performed. A total of 205 patients presenting with BF after RP were included in this study. Imaging findings on 18 F-DCFPyL PET/CT were recorded and correlated with the PSA characteristics at BF and pathological features of the original tumour.ResultsOf the 205 patients, 120 (58.5%) had evidence of abnormal prostate-specific membrane antigen (PSMA) expression compatible with recurrent prostate cancer. Increasing PSA velocity (P = 0.01), International Society of Urological Pathology (ISUP) Grade Group (P = 0.02), lymphovascular invasion (P = 0.05) and nodal positivity (P = 0.02) at the time of RP were more likely to demonstrate PSMA positivity. Multivariable logistic regression revealed a higher PSA level prior to PSMA PET/CT (P < 0.01), adjuvant radiotherapy (P = 0.09), Gleason score ≥8 (P < 0.01) and nodal positivity (P = 0.05) were all predictive of PSMA positivity.Conclusion18 F-DCFPyL PET/CT positivity, both generally and site specific, correlates with PSA and RP pathological factors. Our results echo cohorts focussing on post-RP patients, those imaged with 68 Ga-PSMA and those concerning biochemical persistence. Nomograms that include risk factors for 'PSMA-positive recurrence' in the BF population may increase the catchment of patients with disease confined to the prostate bed or pelvis who have a greater probability of prolonged disease-free survival.
| S-EPMC9540526 | biostudies-literature