scholarly journals Microscopic Review on the Curability and Invasiveness of Heavy Ion Radiotherapy in a Patient with Locally Advanced High-grade Prostate Cancer without Biochemical Recurrence:

2021 ◽  
Vol 71 (1) ◽  
pp. 47-52
Author(s):  
Kohei Kurokawa ◽  
Masamitsu Takatama ◽  
Toshio Fukuda ◽  
Keiji Suzuki ◽  
Masahide Kawamura ◽  
...  
2019 ◽  
Vol 20 (9) ◽  
pp. 2082
Author(s):  
Chiara Zanusso ◽  
Eva Dreussi ◽  
Roberto Bortolus ◽  
Chiara Romualdi ◽  
Sara Gagno ◽  
...  

Up to 30–50% of patients with locally advanced prostate cancer (PCa) undergoing radiotherapy (RT) experience biochemical recurrence (BCR). The immune system affects the RT response. Immunogenetics could define new biomarkers for personalization of PCa patients’ treatment. The aim of this study is to define the immunogenetic biomarkers of 10 year BCR (primary aim), 10 year overall survival (OS) and 5 year BCR (secondary aims). In this mono-institutional retrospective study, 549 Caucasian patients (a discovery set n = 418; a replication set n = 131) were affected by locally advanced PCa and homogeneously treated with RT. In the training set, associations were made between 447 SNPs in 77 genes of the immune system; and 10 year BCR and 10 year OS were tested through a multivariate Cox proportional hazard model. Significant SNPs (p-value < 0.05, q-value < 0.15) were analyzed in the replication set. Replicated SNPs were tested for 5 year BCR in both sets of patients. A polymorphism in the PDL1 gene (rs4143815) was the unique potential genetic variant of 10 year BCR (training set: p = 0.003, HR (95% CI) = 0.58 (0.41–0.83); replication set: p = 0.063, HR (95% CI) = 0.52 (0.26–1.04)) that was significantly associated with 5 year BCR (training set: p = 0.009, HR (95% CI) = 0.59 (0.40–0.88); replication set: p = 0.036, HR (95% CI) = 0.39 (0.16–0.94)). No biomarkers of OS were replicated. rs4143815-PDL1 arose as a new immunogenetic biomarker of BCR in PCa, giving new insights into the RT/immune system interaction, which could be potentially useful in new approaches using anti-PDL1 therapies for PCa.


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 147-147
Author(s):  
Jona Ashok Hattangadi ◽  
Ming-Hui Chen ◽  
Leon Sun ◽  
Anthony Victor D'Amico

147 Background: A digital rectal examination (DRE) is less commonly practiced in the PSA screening era. Whether detection of high-grade prostate cancer (PC) while still clinically localized on DRE can improve survival in men with a normal PSA is unknown. Methods: From the Surveillance, Epidemiology and End Results database, 166,498 men with PC diagnosed between 2004-2008 were identified. Logistic regression was used to identify factors associated with the occurrence of palpable, PSA-occult (PSA <2.5 ng/ml) and Gleason score (GS) 8-10 PC. Factors examined included age at and year of diagnosis and race. Fine and Grays and Cox multivariable regression were performed to analyze whether these factors, treatment and known prognostic factors were associated with the risk of PC-specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: Of 166,498, 685 men (0.4%) had palpable, PSA-occult and GS 8 to 10 PC. Median age and PSA at diagnosis in this group were 68 years [IQR: 61-75] and 1.5 ng/ml [IQR: 1-2], respectively. Most (83%) men were white. Both increasing age (adjusted odds ratio (AOR): 1.02 [95% confidence interval (CI) 1.01-1.03]; p<0.0001) and white race (AOR: 1.26 [95% CI 1.03-1.54]; p =0.03) were associated with palpable, Gleason 8 to 10 PC with normal PSA. Significant factors associated with an increased risk of PCSM and ACM in this cohort are shown in the table. For these 685 men, detecting locally advanced as compared to localized PC on DRE was associated with a significantly lower survival (p = 0.0001). Conclusions: Detecting PSA-occult high-grade PC with DRE while disease remains clinically localized amongst high-risk men (over age 68 and white race) has the potential to improve survival. [Table: see text]


2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 139-139 ◽  
Author(s):  
Sara Moscovita Falzarano ◽  
Ming Zhou ◽  
Paula Carver ◽  
Eric A. Klein ◽  
Robert Dreicer ◽  
...  

139 Background: Taxanes are microtubule-stabilizing drugs used investigationally in adjuvant and neoadjuvant settings of prostate cancer (PCA) treatment in an attempt to improve systemic control of high risk disease. Understanding mechanism of response to taxanes is an essential step in developing novel combination therapies to improve PCA response rates. MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression by binding target messenger RNAs and inhibiting their stability and/or translation. In cancer miRNAs can act as oncogenes and/or tumor suppressor genes. The objective of our study was to identify miRNAs that are affected by neoadjuvant docetaxel in high-risk PCA. Methods: Whole cell RNA was extracted from formalin-fixed paraffin-embedded (FFPE) radical prostatectomy specimens from 8 patients with high grade PCA treated with neoadjuvant docetaxel, 8 high grade untreated PCA and their corresponding untreated non-neoplastic tissue. Tumors were matched by Gleason score, patient age and year of surgery. The expression of 88 cancer-associated miRNAs was then quantified using a PCR-based miRNA microarray assay. Results: Thirty-eight (43%) of the 88 analyzed miRNAs (including miR-205, miR-222, and miR-1) were sgnificantly downregulated in untreated PCA compared with untreated non-neoplastic tissue, and one (miR-183) was upregulated. Twenty (23%) miRNAs (including miR-218, miR-124, and let-7b) were significantly upregulated in treated compared to untreated PCA. The expression levels of 16 of these miRNAs (including miR-9, miR-133b, and miR-27b) were reverted to values similar to untreated non-neoplastic prostatic tissue, as a result of docetaxel treatment. Conclusions: Our results indicate a potential role of miRNAs in PCA response to taxanes. A subset of miRNAs are downregulated in untreated tumors but upregulated in treated PCA to the levels compared to untreated non-neoplastic tissue, suggesting a miRNA modulation towards a non-neoplastic expression profile with neoadjuvant docetaxel treatment. Further studies are underway to evaluate the miRNA-mediated effects of taxanes in PCA.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5080-5080
Author(s):  
David Dewei Yang ◽  
Brandon Arvin Virgil Mahal ◽  
Christopher Sweeney ◽  
Quoc-Dien Trinh ◽  
Felix Yi-Chung Feng ◽  
...  

5080 Background: The clinical implications of a low prostate-specific antigen (PSA) in high-grade prostate cancer are unclear. We examined the prognostic and predictive value of a low PSA in high-grade prostate cancer. Methods: We identified 642,975 patients in the National Cancer Database (n = 491,505) and Surveillance, Epidemiology, and End Results program (n = 151,470) with localized or locally advanced prostate cancer from 2004-2013. Patients were stratified by Gleason score (8-10 vs. ≤7) and PSA (≤2.5, 2.6-4.0, 4.1-10.0, 10.1-20.0, and > 20.0 ng/mL) for analyses. Multivariable Fine-Gray competing risks and Cox regressions were used to analyze prostate-cancer specific mortality (PCSM) and all-cause mortality (ACM), respectively. Results: 5.6% of Gleason 8-10 tumors were diagnosed with PSA ≤2.5 ng/mL. Among Gleason 8-10 disease using PSA 4.1-10.0 ng/mL as referent, PCSM was U-shaped with respect to PSA, with adjusted hazard ratio (AHR) of 1.75 (95% CI 1.05-2.92, P = 0.032) for PSA ≤2.5 ng/mL vs. 1.31, 0.88, and 1.60 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL. In contrast, PCSM was linear for Gleason ≤7 disease with AHR of 0.32 (95% CI 0.10-1.00, P = 0.050) for PSA ≤2.5 ng/mL vs. 1.13, 1.69, and 3.22 for PSA 2.6-4.0, 10.1-20.0, and > 20.0 ng/mL (PGleason*PSA interaction< 0.001). Gleason 8-10 disease with PSA ≤2.5 ng/mL had a much higher risk of PCSM than standard NCCN high-risk disease (AHR 1.92, 95% CI 1.18-3.14, P = 0.009; 47-month PCSM 14.0% vs. 10.5%). For Gleason 8-10 tumors treated with definitive radiotherapy, androgen deprivation therapy (ADT) was associated with decreased ACM for PSA > 2.5 ng/mL (AHR 0.87, 95% CI 0.81-0.94, P < 0.001) but trended toward increased ACM for PSA ≤2.5ng/mL (AHR 1.27, 95% CI 0.89-1.81, P = 0.194; PADT*PSA interaction= 0.026). Conclusions: Low PSA, high-grade prostate cancer appears to be a unique hormone-resistant entity with a high risk of PCSM that responds poorly to standard treatment. Further molecular classification and trials are urgently needed to develop biological insight into this entity and establish new treatment paradigms, potentially including chemotherapy or novel systemic agents.


2020 ◽  
Vol 17 (1) ◽  
pp. S64-S65
Author(s):  
H.L. Bernie ◽  
C.A. Salter ◽  
E. Schofield ◽  
N. Benfante ◽  
J.P. Mulhall

Author(s):  
Christina Niklas ◽  
Matthias Saar ◽  
Alessandro Nini ◽  
Johannes Linxweiler ◽  
Stefan Siemer ◽  
...  

Abstract Purpose A number of observational clinical studies suggest that prior primary tumor treatment favorably influences the course of metastatic prostate cancer (PCa), but its mechanisms of action are still speculative. Here, we describe the long-lasting sensitivity to various forms of androgen deprivation in patients after radical prostatectomy (RP) for locally advanced PCa as one potential mechanism. Methods A consecutive series of 115 radical prostatectomies after inductive therapy for T4 prostate cancer was re-analyzed, and long-term survival, as well as recurrence patterns and responses to different forms of hormonal manipulation, were assessed. Results The estimated biochemical response-free, PCa-specific, and overall survival rates after 200 months were 20%, 65%, and 47% with a median overall survival of 156 months. The majority of patients, although not cured of locally advanced PCa (84/115), showed long-term survival after RP. PCa-specific and overall survival rates of these 84 patients with biochemical recurrence were 61% and 44% at 150 months. Long-term sensitivity to ADT was found to be the main reason for the favorable tumor-specific survival in spite of biochemical recurrence. Conclusions Sensitivity to primary or secondary hormonal manipulation was the main reason for the long-term survival of patients who had not been cured by surgery only. The results suggest that treatment of the primary tumor-bearing prostate delays castration-resistant PCa and enhances the effect of hormonal therapies in a previously unknown manner. The underlying cellular and molecular mechanisms need to be explored in more detailed analyses, which could profoundly impact treatment concepts of locally advanced and metastatic PCa.


Urology ◽  
2000 ◽  
Vol 55 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Isaac J Powell ◽  
Mousumi Banerjee ◽  
Mary Novallo ◽  
Wael Sakr ◽  
David Grignon ◽  
...  

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