Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Minimally Invasive Treatments for Benign Prostatic Hyperplasia: Systematic Review and Network Meta-Analysis

PurposeTo review and to compare indirectly the outcomes of minimally invasive therapies for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia.Materials and MethodsA literature search via Medline and Cochrane Central databases was completed for randomized control studies published between January 2000 to April 2020 for the following therapies: Rezum, Urolift, Aquablation, and prostatic artery embolization (PAE). Data on the following variables were included: International prostate symptom score (IPSS), maximum urinary flow rate, quality of life, and postvoid residual (PVR). Standard mean differences between treatments were compared through a meta-analysis using transurethral resection of the prostate (TURP) to assess differences in treatment effect.ResultsThere was no significant difference in outcomes between therapies for IPSS at the 3, 6, and 12-month follow ups. Although outcomes for Rezum were only available out to 3 months, there were no consistently significant differences in outcomes when comparing Aquablation versus PAE versus Rezum. TURP PVR was significantly better than Urolift at 3, 6, and 12 months. No significant differences in minor or major adverse events were noted.ConclusionAlthough significant differences in outcomes were limited, Aquablation and PAE were the most durable at 12 months. PAE has been well studied on multiple randomized control trials with minimal adverse events while Aquablation has limited high quality data and has been associated with bleeding-related complications.     

Role of surgical treatments in high-grade or advanced gastroenteropancreatic neuroendocrine neoplasms

Over the last 40 years, the incidence and prevalence of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have continued to increase. Compared to other epithelial neoplasms in the same organ, GEP-NENs exhibit indolent biological behavior, resulting in more chances to undergo surgery. However, the role of surgery in high-grade or advanced GEP-NENs is still controversial. Surgery is associated with survival improvement of well-differentiated high-grade GEP-NENs, whereas poorly differentiated GEP-NENs that may benefit from resection require careful selection based on Ki67 and other tissue biomarkers. Additionally, surgery also plays an important role in locally advanced and metastatic disease. For locally advanced GEP-NENs, isolated major vascular involvement is no longer an absolute contraindication. In the setting of metastatic GEP-NENs, radical intended surgery is recommended for patients with low-grade and resectable metastases. For unresectable metastatic disease, a variety of surgical approaches, including cytoreduction of liver metastasis, liver transplantation, and surgery after neoadjuvant treatment, show survival benefits. Primary tumor resection in GEP-NENs with unresectable metastatic disease is associated with symptom control, prolonged survival, and improved sensitivity toward systemic therapies. Although there is no established neoadjuvant or adjuvant strategy, increasing attention has been given to this emerging research area. Some studies have reported that neoadjuvant therapy effectively reduces tumor burden, improves the effectiveness of subsequent surgery, and decreases surgical complications.     

A basal‐enriched microRNA is required for prostate tumorigenesis in a Pten knockout mouse model

MicroRNAs (miRNAs) play important roles in prostate cancer development. However, it remains unclear how individual miRNAs contribute to the initiation and progression of prostate cancer. Here we show that a basal layer‐enriched miRNA is required for prostate tumorigenesis. We identify miR‐205 as the most highly expressed miRNA and enriched in the basal cells of the prostate. Although miR‐205 is not required for normal prostate development and homeostasis, genetic deletion of miR‐205 in a Pten null tumor model significantly compromises tumor progression and does not promote metastasis. In Pten null basal cells, loss of miR‐205 attenuates pAkt levels and promotes cellular senescence. Furthermore, although overexpression of miR‐205 in prostate cancer cells with luminal phenotypes inhibits cell growth in both human and mouse, miR‐205 has a minimal effect on the growth of a normal human prostate cell line. Taken together, we have provided genetic evidence for a requirement of miR‐205 in the progression of Pten null‐induced prostate cancer.     

Tadalafil for the treatment of benign prostatic hyperplasia

Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.

Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).

Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function.     

良性前列腺增生与前列腺慢性炎症的相关性研究进展

良性前列腺增生（BPH）是老年男性常见的泌尿系统疾病，其发病与前列腺慢性炎症之间存在显著相关。感染因子、尿液返流、代谢综合征、衰老过程和自身免疫应答在内的几种刺激，通过相应分子途径引起前列腺免疫细胞的组织定位和组成成分发生广泛改变，从而导致免疫系统失调，之后引发的组织损伤和缓慢愈合，导致了BPH发生和进展。本文通过总结良性前列腺增生与前列腺慢性炎症的相关性的临床研究结果，前列腺免疫细胞在病理生理机制层面与前两者之间的内在联系，以及抗炎药物对BPH-LUTS的干预作用，以其为BPH-LUTS的药物研发提供参考。