Publication date: October 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 10
Author(s): Karim Marzouk, Behfar Ehdaie, Emily Vertosick, Stephen Zappala, Andrew Vickers
Abstract
Objectives
Recent years have seen the development of biomarkers and imaging technologies designed to improve the specificity of PSA. Widespread implementation of imaging technologies, such as mp-MRI raises considerable logistical challenges. Our objective was to evaluate a biopsy strategy that utilizes selective mp-MRI as a follow-up test to biomarkers to improve the detection of significant prostate cancer.
Methods and Materials
We developed a conceptual approach based on the risk calculated from the 4Kscore using results from the US prospective validation study, multiplied by the likelihood ratio of mp-MRI from the PROMIS trial. The primary outcome was Gleason grade ≥ 7 (grade group ≥ 2) cancer on biopsy. Using decision curve analysis, the net benefit was determined for our model and compared with the use of the 4Kscore and mp-MRI independently at various thresholds for biopsy.
Results
For a cut-point of 7.5% risk of high-grade disease, patients with <5% risk from a blood marker would not have risk of significant prostate cancer sufficiently increased by a positive mp-MRI to warrant biopsy; comparably, patients with a risk >23% would not have risk sufficiently reduced by a negative imaging study to forgo biopsy. From the 4Kscore validation study, 46% of men considered for biopsy in the US have risks 5% to 23%. Net benefit was highest for the combined strategy, followed by 4Kscore alone.
Conclusions
Selective mp-MRI in men with intermediate scores on a secondary blood test results in a biopsy strategy that is more scalable than mp-MRI for all men with elevated PSA. Prospective validation is required to demonstrate if the predicted properties of combined blood and imaging testing are empirically confirmed.
Publication date: October 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 10
Author(s): Lingxiao Chen, Wei Xiong, Wei Guo, Shitong Su, Lin Qi, Bisong Zhu, Miao Mo, Huichuan Jiang, Yuan Li
Abstract
Background
Cytoplasmic linker-associated protein 2 (CLASP2) belongs to a family of microtubule plus-end tracking proteins that localize to the distal ends of microtubules and is involved in various microtubule-dependent processes. We previously showed that CLASP2 is involved in the epithelial-to-mesenchymal transition of bladder urothelial cancer. This research aimed to explore the significance of CLASP2 expression as a prognostic marker for muscle-invasive bladder urothelial cancer (MIBC) patients after radical cystectomy-pelvic lymph node dissection (RC-PLND).
Methods
CLASP2 expression was analyzed in 76 benign bladder tissues and 160 MIBC tissues by tissue immunohistochemistry. Survival analysis and multiple regression analysis following propensity score matching were performed to investigate the correlation between high CLASP2 expression and MIBC patients’ survival.
Results
CLASP2 expression was increased in MIBC patients, especially those with high-stage tumors or lymph node metastasis. In the follow-up of MIBC patients after propensity score matching, whether MIBC patients received adjuvant chemotherapy after RC-PLND, high CLASP2 expression was significantly associated with a poor prognosis. MIBC patients with low CLASP2 expression who received adjuvant chemotherapy tended to have an improved survival prognosis.
Conclusion
CLASP2 expression is correlated with malignant progression of MIBC. High CLASP2 expression predicted a poor prognosis for MIBC patients after RC-PLND.
Publication date: October 2019
Source: Urologic Oncology: Seminars and Original Investigations, Volume 37, Issue 10
Author(s): Takehiro Iwata, Shoji Kimura, Mohammad Abufaraj, Florian Janisch, Mehdi Kardoust Parizi, Andrea Haitel, Micheal Rink, Morgan Rouprêt, Harun Fajkovic, Veronica Seebacher, Peter Nyirady, Pierre I. Karakiewicz, Dmitry Enikeev, Leonid M. Rapoport, Yasutomo Nasu, Shahrokh F. Shariat
Abstract
Objectives
To assess the role of the urokinase plasminogen activator (uPA) system as a prognostic biomarker in patients with nonmuscle invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) with or without adjuvant intravesical therapy.
Material and methods
We stained TURB tissue from 827 NMIBC patients with uPA, its receptor (uPAR) and its inhibitor (PAI-1). The status of these markers was categorized as normal vs. overexpressed using the cutoffs of 30% for uPA, 50% for uPAR, and 30% for PAI-1. Multivariable Cox regression analyses were performed to evaluate the prognostic value of these markers.
Results
uPA was overexpressed in 37.7% of patients, uPAR in 44.7% and PAI-1 in 44.6%. Overexpression of these markers was associated with high tumor grade. Within a median follow-up was 60 months (interquartile range: 22–109), uPA (hazard ratio [HR]: 1.40; P = 0.006), uPAR (HR: 1.70; P < 0.001), PAI-1 (HR: 1.35; P = 0.014), and the combination of all 3 markers (HR: 3.38; P < 0.001) were associated with recurrence-free survival (RFS); uPA (HR: 1.68; P = 0.035) and the combination of all 3 markers (HR: 8.79; P = 0.005) were associated with progression-free survival (PFS). The addition of the uPA system to a base model improved the discrimination by 1.3% for RFS and 2.1% for PFS. In subgroup analyses, uPA (HR: 2.19; P = 0.018) was associated with PFS in T1G3 patients and its addition to a base model improved the discrimination by 2.5%. uPA (HR: 1.44; P = 0.019), uPAR (HR: 1.54; P = 0.006), PAI-1 (HR: 1.46; P = 0.013) and the combination of all 3 markers (HR: 3.48; P < 0.001) were associated with RFS in TaG1-2 patients and their addition to a base model improved the discrimination by 2.1%.
Conclusion
uPA, uPAR, and PAI-1 are overexpressed in one-third to half of patients with NMIBC. Their overexpression is an independent prognosticator of RFS and PFS which improved the predictive accuracy of current clinicopathological characteristics. Biomarkers that capture the biological and clinical behavior of individual tumors may help personalize clinical decision-making in patients with NMIBC.