Crosstalk occurs between nerve and cancer cells. These interactions are important for cancer homeostasis and metabolism. Nerve cells influence the tumor microenvironment (TME) and participate in ...metastasis through neurogenesis, neural extension, and axonogenesis. We summarized the past and current literature on the interaction between nerves and cancer, with a special focus on pancreatic ductal adenocarcinoma (PDAC), prostate cancer (PCa), and the role of the nerve growth factor (NGF) in cancer.
We reviewed PubMed and Google Scholar for the relevant literature on the relationship between nerves, neurotrophins, and cancer in general and specifically for both PCa and PDAC.
The NGF helped sustain cancer cell proliferation and evade immune defense. It is a neuropeptide involved in neurogenic inflammation through the activation of several cells of the immune system by several proinflammatory cytokines. Both PCa and PDAC employ different strategies to evade immune defense. The prostate is richly innervated by both the sympathetic and parasympathetic nerves, which helps in both growth control and homeostasis. Newly formed autonomic nerve fibers grow into cancer cells and contribute to cancer initiation and progression through the activation of β-adrenergic and muscarinic cholinergic signaling. Surgical or chemical sympathectomy prevents the development of prostate cancer. Beta-blockers have a high therapeutic potential for cancer, although current clinical data have been contradictory. With a better understanding of the beta-receptors, one could identify specific receptors that could have an effect on prostate cancer development or act as therapeutic agents.
The bidirectional crosstalk between the nervous system and cancer cells has emerged as a crucial regulator of cancer and its microenvironment. Denervation has been shown to be promising in vitro and in animal models. Additionally, there is a potential relationship between cancer and psychosocial biology through neurotransmitters and neurotrophins.
Despite recent awareness of institutional racism, there are still important racial disparities in prostate cancer medical research. We investigated the historical development of research on racial ...disparities and bias.
PubMed was searched for the term 'prostate cancer race' and added key terms associated with racial disparity. As an indicator of scientific interest in the topic, we analyzed whether the number of publications increased linearly as an indicator of growing interest. The linearity is expressed as R
.
The general search term "prostate cancer race" yielded 4507 publications. More specific search terms with ≥12 publications showing a higher scientific interest were found after 2005. The terms with the most publications when added to the general term were "genetic" (n = 1011), "PSA" (n = 995), and "detection" (n = 861). There was a linear increase in publications for "prostate cancer race" (R
= 0.75) since 1980. Specific terms added to the general terms with a high linear increase (R
≥ 0.7) were "screening" (R
= 0.82), "detection" (R
= 0.72), "treatment access" (R
= 0.71), and "trial underrepresentation" (R
= 0.71). However, only a few studies have investigated its association with sexual activity. A combination with "sexual" showed 157 publications but only two years with ≥12 publications/year.
The terms "genetic", "PSA", and "detection" have been the focus of recent research on racial differences in prostate cancer. We found that old stereotypes are still being mentioned but seem to find little interest in the current literature. Further research interest was found in "treatment access". Recently, interest in socioeconomic factors has decreased.
There are few randomized trials to evaluate the use of PSMA-PET in the planning of post-prostatectomy radiotherapy. There are two unresolved questions 1) should we increase the dose to lesions ...visible on PSMA-PET 2) can we reduce dose in the case of a negative PSMA-PET. In this review, we summarize and discuss the available evidence in the literature. We found that in general, there seems to be an advantage for dose-increase, but ta large recent study from the pre-PSMA era didn’t show an advantage for dose escalation. Retrospective studies have shown that conventional doses to PSMA-PET-positive lesions seem sufficient. On the other hand, in the case of a negative PSMA-PET, there is no evidence that dose-reduction is possible. In the future, the combination of PSMA-PET with genomic classifiers could help in better identify patients who might benefit from either dose- de-or -increase. We further need to identify intraindividual references to help identify lesions with higher aggressiveness.
The neutrophil to lymphocyte ratio (NLR) at baseline has been shown to have prognostic value in metastatic prostate cancer. Little is known about the importance of a change in the NLR during ...treatment in patients treated with Radium-223 (223Ra). We investigated the prognostic value of the NLR at baseline and during therapy in patients with metastatic prostate cancer treated with 223Ra and also in patients treated with Docetaxel. We reviewed all patients treated with 223Ra in our center and randomly chosen patients treated with Docetaxel. Patients were stratified according to NLR ≤ 5 and >5 at baseline and at 12 weeks of therapy. The relationship between NLR measured at baseline and at 12 weeks and overall survival (OS) were evaluated. A total of 149 patients treated with 223Ra and 170 with Docetaxel were evaluated. For patients treated with 223Ra, overall survival was significantly better in patients that had both an NLR ≤ 5 at baseline and at 12 weeks. No such effect of NLR was found in patients treated with Docetaxel. In the present study, NLR at baseline and after 12 weeks of therapy was found to be prognostic factor in patients treated with 223Ra but not in those treated with Docetaxel.
We analyzed the rate of preserved potency after prostate brachytherapy (PB) with radioactive seeds and the impact of patient comorbidities on post-PB erectile dysfunction (ED).
We included 627 ...patients who were assessed for pre- and postimplant potency between 2005 and 2017. Assessment was based on the Common Terminology Criteria for Adverse Events Scale (CTCAEs). Logistic regression models were used to assess clinical predictors of preserved potency after PB defined as having sufficient erections for sexual activity with or without the need of oral pharmacologic assistance. Covariates included age, diabetes (DM), hypertension (HTN), dyslipidemia (DLP), coronary artery disease (CAD), International Prostate Symptom Score (IPSS), prostate volume, and Cancer of the Prostate Risk Assessments (CAPRA) score. Patients on androgen deprivation therapy or using five alpha reductase inhibitors were excluded from analyses.
Post-PB potency was assessed at an average of 6 months (n = 627), 1 year (n = 538), 2 years (=440), 4 years (n = 272), and 5 years (n = 124). At 2 and 5 years, post-PB potency was preserved in 87% and 84% of patients, respectively. When adjusting for all available covariates, advanced age, pre-PB potency, and the presence of vascular comorbidities (HTN, DM, and DLP) were all predictors of potency at 2 years after PB (all p < 0.01). When performing a sensitivity analysis for vascular comorbidities, the presence of DM had the strongest impact on ED than either HTN or DLP (p < 0.01).
More than 84% of patients had preserved potency 5 years after PB. Advanced age, pre-PB potency, and vascular comorbidities had a statistically significant impact on potency after PB.
We present a case of a patient with recurrent prostate cancer after treatment for favorable intermediate risk cancer. There was an exceptionally steep increase in PSA from <0.5 to 130ng/mL in 27 ...months accompanied with the development of bone metastasis. The PSA increase was unexpected. We suspect that this unusual development of metastases must have been caused by an impairment of the immune system caused by his IgG4 disease, and this may have allowed residual prostate cancer cells in the prostate to spread quickly. The influence of IgG4 on cancer is debated.
The impact of statin use on localized prostate cancer (PCa) remains controversial, especially for patients treated with radiation therapy. We assessed the impact of statin use on biochemical ...recurrence (BCR) in patients treated for PCa with different modalities of radiation therapy. We evaluated 3555 patients undergoing radiation therapy between January 2001 and January 2022. The impact of statin use on BCR was analyzed for three treatment groups: external beam radiotherapy (EBRT), low-dose-rate seed brachytherapy (LDR), and EBRT plus high-dose-rate brachytherapy (EBRT + HDR). Median follow-up was 52 months among 1208 patients treated with EBRT, 1679 patients treated with LDR, and 599 patients treated with EBRT + HDR. A total of 1544 (43%) patients were taking a statin at the time of treatment, and 497 (14%) patients were in the D’Amico high-risk group. Only intermediate-risk patients treated with LDR fared better with statin use in univariate analysis (p = 0.025). This association was not significant in multivariate analysis (HR 0.44, 95% CI 0.18–1.10, p = 0.06). Statin use was not associated with a reduced risk of BCR in patients treated with radiation therapy. In the era of precision medicine, further investigation is needed to assess the benefit of statins in well-defined patients.
We analyzed the influence of the neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) on the biochemical recurrence (BCR) in low-intermediate risk prostate cancer (PCa). A total of ...604 patients treated with exclusive brachytherapy for low- and intermediate-risk cancers were included in this study. No patient received either androgen deprivation or brachytherapy as a boost. BCR was defined according to the Phoenix definition (nadir prostatic specific antigen (PSA) +2). The median follow-up was 60 months (IQR 44-48 months). An NLR > 3 was more frequent in statin users (
= 0.025), but not in diabetics (
= 0.079). In univariate analysis (UVA) and multivariate analysis (MVA), a NLR > 3 (MVA
= 0.03), as well as Cancer of the Prostate Risk Assessment (CAPRA) low- vs. intermediate-risk (MVA
= 0.04), were predictive of BCR. When combining the NLR score with the CAPRA risk group, CAPRA intermediate risk patients with an NLR ≤ 3 (
= 157) had the worst (
= 0.0276) BCR rates, with a 5-year recurrence-free survival (
= 0.004, Bonferroni correction for six comparisons
= 0.024). We were able to identify a subgroup of PCa patients with CAPRA intermediate-risk and an NLR ≤ 3 who had worse BCR. This is in contrast to most other cancers, which have a worse prognosis when the NLR is high.
To report the toxicity outcome in patients with localized prostate cancer undergoing (125)I permanent-seed brachytherapy (BT) according to a urethra-sparing, intraoperative (IO), real-time planned ...conformal technique.
Data were analyzed on 250 patients treated consecutively for low- or intermediate-risk prostate cancer between 2005 and 2009. The planned goal was urethral V(150) = 0. Acute and late genitourinary (GU), gastrointestinal (GI), and erectile toxicities were scored with the International Prostate Symptom Score (IPSS) questionnaire and Common Terminology Criteria for Adverse Events (version 3.0). Median follow-up time for patients with at least 2 years of follow-up (n = 130) was 34.4 months (range, 24-56.9 months).
Mean IO urethra V(150) was 0.018% ± 0.08%. Mean prostate D(90) and V(100) on day-30 computed tomography scan were 158.0 ± 27.0 Gy and 92.1% ± 7.2%, respectively. Mean IPSS peak was 9.5 ± 6.3 1 month after BT (mean difference from baseline IPSS, 5.3). No acute GI toxicity was observed in 86.8% of patients. The 3-year probability of Grade ≥2 late GU toxicity-free survival was 77.4% ± 4.0%, with Grade 3 late GU toxicity encountered in only 3 patients. Three-year Grade 1 late GI toxicity-free survival was 86.1% ± 3.2%. No patient presented Grade ≥2 late GI toxicity. Of patients with normal sexual status at baseline, 20.7% manifested Grade ≥2 erectile dysfunction after BT. On multivariate analysis, elevated baseline IPSS (p = 0.016) and high-activity sources (median 0.61 mCi) (p = 0.033) predicted increased Grade ≥2 late GU toxicity.
Urethra-sparing IO BT results in low acute and late GU toxicity compared with the literature. High seed activity and elevated IPSS at baseline increased long-term GU toxicity.
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