Prostate Cancer最新文献

This study evaluated the effects of docetaxel and androgen receptor signaling inhibitors as second-line treatments in patients with castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment. This study retrospectively evaluated the clinical outcomes of second-line treatment with docetaxel or androgen receptor signaling inhibitor in patients with castration-resistant prostate cancer who received first-line treatment with androgen receptor signaling inhibitors. Clinical backgrounds and outcomes were compared between docetaxel and androgen receptor signaling inhibitors as second-line treatment. Of 59 patients, 21 (35.6%) and 38 (64.4%) received docetaxel and androgen receptor signaling inhibitors as second-line treatment after first-line treatment with androgen receptor signaling inhibitors, respectively. In the second-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitor than with docetaxel (17 versus 6 months, P=0.014). In the first-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitors than with docetaxel (32 versus 25 months, P=0.014); however, no significant difference was found in the overall survival. Multivariate analysis revealed that there was no significant association between second-line treatment and survival, and first-line treatment with abiraterone was identified as a prognostic factor for progression-free survival. Subgroup analysis showed that the abiraterone-enzalutamide sequence was more effective than the other three sequences for progression-free survival and overall survival. This study suggests that second-line treatment with an androgen receptor signaling inhibitor for castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment may be more beneficial, particularly with abiraterone as the upfront treatment.

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI.

Methods: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [¹¹C]-PBR28. [¹¹C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps.

Results: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex.

Conclusions: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

Background: The knowledge of risk factors and complications related to extended pelvic lymph node dissection (ePLND) during radical prostatectomy can help selecting patients who will benefit the most with lymph node dissection concomitant to radical prostatectomy.

Materials and methods: Retrospective cohort evaluating 135 patients with PC, with a high risk for lymph node metastasis, submitted to ePLND by a single surgeon between 2013 and 2019, performed either by the laparoscopic or laparoscopic robot-assisted approach. Data related to complications were properly recorded using the Martin's criteria and were classified by the Satava and Clavien-Dindo-Strasberg methods. Logistic regression was used to determine predictors of complications related to ePLND.

Results: The mean number of lymph nodes removed was 10.2 ± 4.9, and in 28.2%, they were positive for metastasis. There were five intraoperative complications (4%), all in patients operated by laparoscopic approach. There were nine severe postoperative complications (7.3%), four of which occurred after postoperative day 30. Three patients (2.4%) had thromboembolic complications and five patients (4.0%) had lymphocele that required treatment. There was a correlation between the American Society of Anesthesiologists (ASA) physical status classification and postoperative complications (p=0.06), but it was not possible to identify statistically significant predictors.

Conclusion: ePLND during radical prostatectomy has a low rate of intraoperative complications and may change prostate cancer staging. Postoperative complications, especially venous thromboembolism and lymphocele, need to be monitored even in the late postoperative period.

Background: The evaluation of tumour-infiltrating lymphocytes (TILs) in solid malignancies has yielded insights into immune regulation within the tumour microenvironment and has also led to the development and optimisation of adoptive T cell therapies.

Objectives: This study examined the in vitro expansion of TILs from prostate adenocarcinoma, as a preliminary step to evaluate the potential of TILs for adoptive T cell therapy. Design, Setting, and Participants. Malignant and adjacent nonmalignant tissues were obtained from fifteen men undergoing radical prostatectomy. Interventions. There were no study interventions. Outcome Measurements and Statistical Analysis. Expanded cells were analysed by flow cytometry, and the data was assessed for associations between cell subpopulations and expansion rate.

Results: Tumour-infiltrating lymphocytes could be expanded to numbers that would be needed to generate a therapeutic infusion product from nine of 15 malignant specimens (60%). The CD4⁺ T cells predominated over CD8⁺ T cells (median 56.8% CD4⁺, 30.0% CD8⁺), and furthermore, faster TIL expansion was associated with a higher proportion of CD4⁺ T cells (median 69.8% in faster-growing cultures; 36.8% in slower-growing cultures). A higher proportion of CD3^-CD56⁺ cells versus CD3⁺ cells was associated with slower TIL expansion in cultures from malignant specimens (median 13.3% in slower-growing cultures versus 2.05% in faster-growing cultures), but not from nonmalignant specimens.

Conclusions: The expansion of TILs for potential therapeutic use is feasible. Our findings also indicate that further examination of TILs from prostate adenocarcinomas may yield insights into mechanisms of regulation of T cells within the tumour microenvironment. Further research is required to evaluate their therapeutic potential.

Materials and methods: This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test.

Results: For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001).

Conclusions: Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.

Background: In 2018, the US Preventive Services Task Force recommended that PSA screening for prostate cancer involve men aged 55-69, based on a personal decision following consultation with a health professional. PSA screening in men aged 70 or older should only occur if symptoms exist. This study identifies the association between having a PSA test in the past two years and whether or not there was consultation with a health professional about the benefits and/or harms of PSA screening.

Methods: Analyses were based on data involving men aged 40 years or older, who responded to PSA related questions in the 2018 BRFSS survey.

Results: Approximately 32.0% (14.6% for ages 40-54, 41.7% for ages 55-69, and 49.8% for ages 70 years and older) of respondents had a PSA test in the past two years. Approximately 81.7% of these men had talked with a health professional about the benefits and/or harms of PSA screening, with 42.4% having discussed the benefits and harms, 54.6% having discussed the benefits only, and 3.0% having discussed the harms only. The odds of a PSA test in the past two years in men having talked with a health professional about the benefits and harms of the test versus no talk are 10.1 (95% CI 9.3-10.8), in men who talked with a health professional about the benefits only versus no talk are 10.8 (95% CI 10.0-11.6), and in men who talked with a health professional about the harms only versus no talk are 3.9 (95% CI 2.9-5.1).

Conclusion: PSA screening is most common in men aged 70 or older, which is counter to the US Preventive Task Force recommendation. Most men having a PSA test have talked with a health professional about the test, but the talks tended to focus on just the benefits of screening and not both potential benefits and harms.

Aim: Prostate cancer (PCa) is the second most common nonskin malignancy and the second most common cause of cancer-related deaths in men. The most common site of metastasis in PCa is the axial skeleton which may lead to back pain or pathological fractures. Hematogenous spread to the brain and involvement of the central nervous system (CNS) are a rare occurrence. However, failed androgen deprivation therapy (ADT) may facilitate such a spread resulting in an advanced metastatic stage of PCa, which carries a poor prognosis.

Methods: In this systematic review, we searched the PubMed, Scopus, and Web of Science online databases based on the PRISMA guideline and used all the medical subject headings (MeSH) in terms of the following search line: ("Brain Neoplasms" OR "Central Nervous System Neoplasms") and ("Prostatic Neoplasms" OR "Prostate"). Related studies were identified and reviewed.

Results: A total of 59 eligible studies (902 patients) were included in this systematic review. In order to gain a deeper understanding, we extracted and presented the data from included articles based on clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic status of PCa patients having BMs.

Conclusion: We have demonstrated the current knowledge regarding the mechanism, clinical manifestations, diagnostic methods, therapeutic approaches, and prognosis of BMs in PCa. These data shed more light on the way to help clinicians and physicians to understand, diagnose, and manage BMs in PCa patients better.

Background: Genetic factors are one of the significant contributors to prostate cancer (PCa) development, and hereditary prostate cancer 2 (HPC2) locus gene ELAC2 is considered a PCa susceptibility region. The HPC2/ELAC2 gene has been identified by linkage analysis in familial prostate cancer patients in the United States but has never been studied in Burkina Faso. The objective of the present study was to analyze the carriage of the C650T (Ser217Leu) and G1621A (Ala541Thr) mutations of the ELAC2 gene and the risk factors in prostate cancer patients in Burkina Faso.

Methods: This case-control study included 76 participants, including 38 histologically confirmed prostate cancer cases and 38 healthy controls without prostate abnormalities. PCR combined with restriction fragment length polymorphism (RFLP) was used to characterize the genotypes of the Ser217Leu and Ala541Thr polymorphisms of the ELAC2 gene. The correlations between the different genotypes and risk factors for prostate cancer were investigated.

Results: The C650T mutation was present in 44.73% of prostate cancer cases and 47.37% of controls. The G1621A mutation was present in 26.32% of prostate cancer cases and 15.79% of controls. We did not detect an association between prostate cancer risk and the Ser217Leu (p=0.972) and Ala541Thr (p=0.267) variants of the ELAC2 gene. Also, the two ELAC2 SNPs did not correlate with clinical stage, prostate-specific antigen (PSA) level at diagnosis, or the Gleason score on biopsies. However, we found that 100% of homozygous carriers of the T650 mutation have an A1621 mutation (p ≤ 0.001).

Conclusion: Ser217Leu and Ala541Thr polymorphisms of ELAC2, considered alone or in combination, are not associated with prostate cancer risk.

Purpose: This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated.

Results: In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23-1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population.

Conclusions: HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.