scholarly journals The Association between Plasma Levels of Intact and Cleaved uPAR Levels and the Risk of Biochemical Recurrence after Radical Prostatectomy for Prostate Cancer

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 877
Author(s):  
Hein Vincent Stroomberg ◽  
Gitte Kristensen ◽  
Kasper Drimer Berg ◽  
Solvej Lippert ◽  
Klaus Brasso ◽  
...  

Radical prostatectomy (RP) is a curatively intended treatment option for clinically localized non-metastatic prostate cancer (PCa). Novel biomarkers could refine treatment choice based on a better identification of men at risk of biochemical recurrence (BCR) following therapy. The urokinase plasminogen activator receptor (uPAR) system is a promising biomarker of aggressiveness in many cancers. The predictive value of uPAR after curatively intended treatment for PCa remains to be elucidated. This was a prospective evaluation of uPAR analysis in men with prostate cancer (Copenhagen uPAR prostate cancer (CuPCA) database). Risk of BCR following RP was analyzed using cumulative incidences with competing risk and tested with Gray’s test. Associations between quartile groups of uPAR levels and BCR were assessed with uni- and multivariate Cox proportional hazards. In total, 532 men were included. With more advanced tumor stage, Gleason score (GS), and prostate-specific antigen (PSA) the uPAR I–III + II–III plasma levels increased. Quartile levels of plasma uPAR I–III, I–III + II–III showed no significant association between the risk of BCR and the plasma uPAR levels in uni- and multivariate analysis. Despite increased levels of uPAR I–III + II–III in advanced tumor stage, intact and cleaved uPAR levels were not associated with BCR and are not predictive biomarkers for BCR following curatively intended treatment of PCa. It is unlikely that further studies of uPAR in RP treated patients is needed.

Author(s):  
Chun-Yu Hsieh ◽  
Ying-Erh Chou ◽  
Chia-Yen Lin ◽  
Shian-Shiang Wang ◽  
Ming-Hsien Chien ◽  
...  

Prostate cancer is among the most common malignant tumors worldwide. Matrix metalloproteinase (MMP)-11 is involved in extracellular matrix degradation and remodeling and plays an essential role in cancer development and metastasis. This study investigated the association of MMP-11 polymorphisms with the clinicopathological characteristics and biochemical recurrence of prostate cancer. Five single-nucleotide polymorphisms (SNPs) of the MMP-11 were analyzed in 578 patients with prostate cancer through real-time polymerase chain reaction analysis. A prostate-specific antigen level of >10 ng/mL, Gleason grade groups 4 + 5, advanced tumor stage, lymph node metastasis, invasion, and high-risk D’Amico classification were significantly associated with biochemical recurrence in the patients (p < 0.001). MMP-11 rs131451 “TC + CC” polymorphic variants were associated with advanced clinical stage (T stage; p = 0.007) and high-risk D’Amico classification (p = 0.015) in patients with biochemical recurrence. These findings demonstrate that MMP-11 polymorphisms were not associated with prostate cancer susceptibility; however, the rs131451 polymorphic variant was associated with late-stage tumors and high-risk D’Amico classification in prostate cancer patients with biochemical recurrence. Thus, the MMP-11 SNP rs131451 may contribute to the tumor development in prostate cancer patients with biochemical recurrence.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Lindsay S. Rowe ◽  
Stephanie Harmon ◽  
Adam Horn ◽  
Uma Shankavaram ◽  
Soumyajit Roy ◽  
...  

Abstract Background Prostate Membrane Specific Antigen (PSMA) positron emission tomography (PET) and multiparametric MRI (mpMRI) have shown high accuracy in identifying recurrent lesions after definitive treatment in prostate cancer (PCa). In this study, we aimed to outline patterns of failure in a group of post-prostatectomy patients who received adjuvant or salvage radiation therapy (PORT) and subsequently experienced biochemical recurrence, using 18F-PSMA PET/CT and mpMRI. Methods PCa patients with biochemical failure post-prostatectomy, and no evident site of recurrence on conventional imaging, were enrolled on two prospective trials of first and second generation 18F-PSMA PET agents (18F-DCFBC and 18F-DCFPyL) in combination with MRI between October 2014 and December 2018. The primary aim of our study is to characterize these lesions with respect to their location relative to previous PORT field and received dose. Results A total of 34 participants underwent 18F-PSMA PET imaging for biochemical recurrence after radical prostatectomy and PORT, with 32/34 found to have 18F-PSMA avid lesions. On 18F-PSMA, 17/32 patients (53.1%) had metastatic disease, 8/32 (25.0%) patients had locoregional recurrences, and 7/32 (21.9%) had local failure in the prostate fossa. On further exploration, we noted 6/7 (86%) of prostate fossa recurrences were in-field and were encompassed by 100% isodose lines, receiving 64.8–72 Gy. One patient had marginal failure encompassed by the 49 Gy isodose. Conclusions 18F-PSMA PET imaging demonstrates promise in identifying occult PCa recurrence after PORT. Although distant recurrence was the predominant pattern of failure, in-field recurrence was noted in approximately 1/5th of patients. This should be considered in tailoring radiotherapy practice after prostatectomy. Trial registrationwww.clinicaltrials.gov, NCT02190279 and NCT03181867. Registered July 12, 2014, https://clinicaltrials.gov/ct2/show/NCT02190279 and June 8 2017, https://clinicaltrials.gov/ct2/show/NCT03181867.


2018 ◽  
Author(s):  
Dunia Khaled ◽  
Scott Delacroix ◽  
Brian Chapin

After receiving local treatment, many patients will develop a biochemical recurrence (BCR) in the absence of detectable distant disease (cM0) and comprise a significant proportion (20.1%) of prostate cancer disease states. The natural history of patients with BCR ranges from those with indolent, nonprogressive, slow prostate-specific antigen (PSA)-only progression to those ultimately destined to develop metastases and progress to a cancer-specific death. Pathologic predictors of BCR, clinical progression, and cancer-specific mortality are well established in the literature, although multiple novel predictors are emerging, which are highlighted. Traditional imaging cannot reliably distinguish local versus distant microscopic metastasis at the PSA levels that have been shown to confer survival advantage for salvage radiation therapy. We review past and present imaging standards and discuss novel imaging modalities, which may improve staging and offer opportunity for novel salvage therapies, including salvage lymph node dissection and stereotactic beam radiation therapy. With an emphasis on BCR after radical prostatectomy, both curative and palliative treatments are reviewed. This review contains 7 figures, 6 tables and 73 references Key words: biochemical recurrence, clinically undetectable metastases, molecular imaging, monitoring treatment response, prostate cancer, radical prostatectomy, rising prostate-specific antigen, salvage lymph node dissection, salvage radiation  


2005 ◽  
Vol 23 (32) ◽  
pp. 8198-8203 ◽  
Author(s):  
Andrew J. Stephenson ◽  
James A. Eastham

Patients with isolated local recurrence of prostate cancer after radiation therapy may potentially be cured of their disease by salvage radical prostatectomy (RP). The stage-specific 5-year cancer-control rates of salvage RP resemble those of standard RP. However, the ability to effectively administer salvage treatment to patients with radiorecurrent disease is compromised by the lack of diagnostic tests with sufficient sensitivity and specificity to detect local recurrence at an early stage while it is amenable to local salvage therapy. By the time biochemical recurrence is declared using the current American Society for Therapeutic Radiology and Oncology definition, the majority of patients have advanced local disease, precluding successful local salvage therapy. When salvage RP is performed at prostate-specific antigen levels of 10 ng/mL or less, an estimated 70% of patients are free of disease at 5 years. With better patient selection and technical modifications, the morbidity associated with salvage RP has improved substantially. Rates of urinary incontinence and anastomotic stricture are acceptable, although one third of patients will experience these complications. Salvage cryotherapy is a minimally invasive alternative to salvage RP, but cancer-control rates appear to be inferior and it does not provide a clear advantage over salvage RP in terms of reduced morbidity. Patients with local recurrence after radiation therapy are at increased risk of metastatic progression and cancer-specific mortality. Currently, salvage RP represents the only curative treatment option for these patients. Salvage RP may favorably alter the natural history of biochemical recurrence after radiation therapy, but it must be instituted early in the course of recurrent disease to be effective.


2016 ◽  
Vol 103 (2) ◽  
pp. 204-208 ◽  
Author(s):  
Burak Arslan ◽  
Özkan Onuk ◽  
İsmet Hazar ◽  
Muammer Aydın ◽  
Nusret Can Çilesiz ◽  
...  

Purpose To assess the diagnostic capability of serum endocan level in association with clinicopathologic features and its impact on biochemical progression-free survival in patients with prostate cancer (PCa). Methods A total of 86 patients with localized prostate cancer were treated with open radical prostatectomy (RP). The control group included 80 patients who were referred to the urology outpatient clinic with normal rectal examination and prostate-specific antigen (PSA) levels. The patients’ characteristics, baseline PSA value, and serum endocan levels were recorded. The patients were followed up with the measurement of PSA concentration every 3 months during the first year, thereafter every 6 months until 5 years, then yearly after surgery. The primary endpoint of follow-up was the time of biochemical recurrence. Results The median serum endocan levels were 3.14 ng/mL in the RP group and 2.98 ng/mL in the control group (p = 0.122). A total of 86 patients who underwent RP for PCa were divided into 2 groups based on a cutoff serum endocan level of 1.8 ng/mL. The distribution of Gleason score and biochemical failure rate were significantly higher in patients with serum endocan ≥1.8 ng/mL (p = 0.031 and p = 0.047). The biochemical recurrence-free time for endocan ≥1.8 ng/mL and <1.8 ng/mL were 38 and 56 months, respectively (p = 0.041). Spearman correlation analysis showed a linear relationship between endocan expression and Gleason score (p = 0.025, p = 0.511). Multivariate analysis revealed that elevated serum endocan level (≥1.8 ng/mL) was a significant predictor of biochemical progression-free survival (hazard ratio 2.44; 95% confidence interval 1.78-3.23; p = 0.001). Conclusions The current study indicates that endocan has a close relationship with tumor recurrence in PCa.


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