Sexual dysfunction associated with prostate cancer treatment in Japanese men: a qualitative research

Purpose We investigated the experiences of Japanese men with sexual dysfunction associated with various prostate cancer treatments. Methods We included 38 Japanese men who underwent the following initial treatments for prostate cancer: radical prostatectomy (n = 10), external beam radiotherapy (n = 12), brachytherapy (n = 5), and androgen deprivation therapy (n = 11). Semi-structured interviews were conducted regarding sexual dysfunction associated with prostate cancer treatment. Data were analyzed using a content analysis method. To obtain a unique experience for each treatment, we confirmed and organized the treatment method from which the code that constituted each category was derived. The category reliability was calculated based on Scott’s formula for the matching rate of the classification by three qualitative researchers. The criterion for good reliability was set at 70%. Results Japanese men with sexual dysfunction associated with prostate cancer treatments experienced the following: a desire to maintain sexual function and conflict in decision-making concerning the initial treatment for prostate cancer; a loss of values related to sexual dysfunction; an uncertainty regarding the consequences of sexual dysfunction; a sense of calm with fewer adverse effects of sexual dysfunction at the early treatment stage; an effort to accept sexual dysfunction; and management of their changed body at the later treatment stages. The concordance rates for the categories were 70% and 78%. Additionally, there were glimpses of experiences common to all treatments and trends in treatment-specific experiences. Conclusion It is necessary to provide care based on the experience of Japanese men with sexual dysfunction after prostate cancer treatment.

Androgens in SARS-CoV-2 Coronavirus Infections

Recent molecular biology findings have shown that for the penetration of the SARS-CoV-2 coronavirus into host cells, a key role is played by protease serine 2, the activity of which is dependent on androgens. The important role of androgens is also evidenced by clinical observations that men in some age categories are infected by this novel coronavirus up to two times more frequently than women. In addition, men with androgenic alopecia tend to have more serious clinical courses, while men with androgen deprivation as a result of prostate cancer treatments tend to have milder courses. This is in line with the fact that preadolescent children are only rarely sickened with serious forms of SARS-CoV-2 infections. Even though these observations may be explained by other factors, many authors have hypothesized that lowered androgen levels and blocking their activity using anti-androgen medication may moderate the course of the viral infection in intermediately- to critically-affected cases. Clearly, it would be important for androgen deprivation to block not just gonadal androgens, but also adrenal androgens. On the other hand, low androgen levels are considered to be a risk factor for the course of SARS-CoV-2 infections, either because low androgen levels have a general effect on anabolic-catabolic equilibrium and energy metabolism, or because of the ability of testosterone to modify the immune system. It is not yet clear if infection with this novel coronavirus might induce hypogonadism, leading to undesirable side effects on male fertility.

Exploring the Value of BRD9 as a Biomarker, Therapeutic Target and Co-Target in Prostate Cancer

Background and aims: Despite recent advances in advanced prostate cancer treatments, clinical biomarkers or treatments for men with such cancers are imperfect. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterise BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA M.expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression, and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signalling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

End-to-end test for fractionated online adaptive MR-guided radiotherapy using a deformable anthropomorphic pelvis phantom

Objective: In MR-guided radiotherapy (MRgRT) for prostate cancer treatments inter-fractional anatomy changes such as bladder and rectum fillings may be corrected by an online adaption of the treatment plan. To clinically implement such complex treatment procedures, however, specific end-to-end tests are required that are able to validate the overall accuracy of all treatment steps from pre-treatment imaging to dose delivery. Approach: In this study, an end-to-end test of a fractionated and online adapted MRgRT prostate irradiation was performed using the so-called ADAM-PETer phantom. The phantom was adapted to perform 3D polymer gel (PG) dosimetry in the prostate and rectum. Furthermore, thermoluminescence detectors (TLDs) were placed at the center and on the surface of the prostate for additional dose measurements as well as for an external dose renormalization of the PG. For the end-to-end test, a total of five online adapted irradiations were applied in sequence with different bladder and rectum fillings, respectively. Main results: A good agreement of measured and planned dose was found represented by high γ-index passing rates (3 %⁄ 3 mm criterion) of the PG evaluation of 98.9 % in the prostate and 93.7 % in the rectum. TLDs used for PG renormalization at the center of the prostate showed a deviation of -2.3 %. Significance: The presented end-to-end test, which allows for 3D dose verification in the prostate and rectum, demonstrates the feasibility and accuracy of fractionated and online-adapted prostate irradiations in presence of inter-fractional anatomy changes. Such tests are of high clinical importance for the commissioning of new image-guided treatment procedures such as online adaptive MRgRT.

Minimally invasive magnetic resonance image-guided prostate interventions

Whole gland prostate cancer treatment, i.e. radical prostatectomy or radiation therapy, is highly effective but also comes with a significant impact on quality of life and possible overtreatment in males with low to intermediate risk disease. Minimal-invasive treatment strategies are emerging techniques. Different sources of energy are used to aim for targeted treatment in order to reduce treatment-related complications and morbidity. Imaging plays an important role in targeting and monitoring of treatment approaches preserving parts of the prostatic tissue. Multiparametric magnetic resonance imaging (mpMRI) is widely used during image-guided interventions due to the multiplanar and real-time anatomical imaging while providing an improved treatment accuracy. This review evaluates the available image-guided prostate cancer treatment options using MRI or magnetic resonance imaging/transrectal ultrasound (MRI/TRUS)-fusion guided imaging. The discussed minimal invasive image-guided prostate interventions may be considered as safe and feasible partial gland ablation in patients with (recurrent) prostate cancer. However, most studies focusing on minimally invasive prostate cancer treatments only report early stages of research and subsequent high-level evidence is still needed. Ensuring a safe and appropriate utilization in patients that will benefit the most, and applied by physicians with relevant training, has become the main challenge in minimally invasive prostate cancer treatments.

BRD9 Expression, Alteration, Survival And Pathway Analysis In 11 Independent Prostate Cancer Cohorts

Background and aims: Despite recent advances in advanced prostate cancer treatments, there are no clinically useful biomarkers or treatments for men with such cancers. Targeted therapies have shown promise, but there remain fewer actionable targets in prostate cancer than in other cancers. This work aims to characterize BRD9, currently understudied in prostate cancer, and investigate its co-expression with other genes to assess its potential as a biomarker and therapeutic target in human prostate cancer. Materials and methods: Omics data from a total of 2053 prostate cancer patients across 11 independent datasets were accessed via Cancertool and cBioPortal. mRNA expression and co-expression, mutations, amplifications, and deletions were assessed with respect to key clinical parameters including survival, Gleason grade, stage, progression and treatment. Network and pathway analysis was carried out using Genemania, and heatmaps were constructed using Morpheus. Results: BRD9 is overexpressed in prostate cancer patients, especially those with metastatic disease. BRD9 expression did not differ in patients treated with second generation antiandrogens versus those who were not. BRD9 is co-expressed with many genes in the SWI/SNF and BET complexes, as well as those in common signaling pathways in prostate cancer. Summary and conclusions: BRD9 has potential as a diagnostic and prognostic biomarker in prostate cancer. BRD9 also shows promise as a therapeutic target, particularly in advanced prostate cancer, and as a co-target alongside other genes in the SWI/SNF and BET complexes, and those in common prostate cancer signalling pathways. These promising results highlight the need for wider experimental inhibition and co-targeted inhibition of BRD9 in vitro and in vivo, to build on the limited inhibition data available.

Advanced prostate cancer experimental radioactive treatment—clinical trial decision making: patient experiences

ObjectivesNested qualitative studies within clinical trials provide the opportunity to better understand participant experiences of participation and identify areas where improved support is required. The purpose of this qualitative study is to describe the lived experiences of men with advanced prostate cancer participating in the TheraP trial; a randomised trial of 177Lu-PSMA-617 compared with cabazitaxel chemotherapy.MethodsFifteen men with advanced prostate cancer were recruited from the TheraP clinical trial and interviewed at three time points during the trial. Interviews were inductively analysed using thematic analysis. This research paper reports the results from the baseline interview at commencement of the trial, focusing specifically on participants’ enrolment experiences.ResultsFour themes were identified representing the lived experiences of men with advanced prostate cancer deciding to participate in the TheraP trial: (1) hoping to survive; (2) needing to feel informed; (3) choosing to participate and (4) being randomised. The process of deciding to enrol in a clinical trial is filled with indecision, emotional difficulties and focused on a desire to live.ConclusionsFor men with advanced prostate cancer, the experience of deciding to enrol in a clinical trial is principally driven by a desire to survive but interlinked with the need to make an informed decision as participants in this study expressed a preference for allocation to the experimental arm. Men seeking to enrol in clinical trials of new prostate cancer treatments would benefit from improved informational and decision support.Trial registration numberNCT03392428, ANZUP1603.

Personalized Treatment Planning Automation in Prostate Cancer Radiation Oncology: A Comprehensive Dosimetric Study

BackgroundIn radiation oncology, automation of treatment planning has reported the potential to improve plan quality and increase planning efficiency. We performed a comprehensive dosimetric evaluation of the new Personalized algorithm implemented in Pinnacle3 for full planning automation of VMAT prostate cancer treatments.Material and MethodsThirteen low-risk prostate (without lymph-nodes irradiation) and 13 high-risk prostate (with lymph-nodes irradiation) treatments were retrospectively taken from our clinical database and re-optimized using two different automated engines implemented in the Pinnacle treatment system. These two automated engines, the currently used Autoplanning and the new Personalized are both template-based algorithms that use a wish-list to formulate the planning goals and an iterative approach able to mimic the planning procedure usually adopted by experienced planners. In addition, the new Personalized module integrates a new engine, the Feasibility module, able to generate an “a priori” DVH prediction of the achievability of planning goals. Comparison between clinically accepted manually generated (MP) and automated plans generated with both Autoplanning (AP) and Personalized engines (Pers) were performed using dose-volume histogram metrics and conformity indexes. Three different normal tissue complication probabilities (NTCPs) models were used for rectal toxicity evaluation. The planning efficiency and the accuracy of dose delivery were assessed for all plans.ResultsFor similar targets coverage, Pers plans reported a significant increase of dose conformity and less irradiation of healthy tissue, with significant dose reduction for rectum, bladder, and femurs. On average, Pers plans decreased rectal mean dose by 11.3 and 8.3 Gy for low-risk and high-risk cohorts, respectively. Similarly, the Pers plans decreased the bladder mean doses by 7.3 and 7.6 Gy for low-risk and high-risk cohorts, respectively. The integral dose was reduced by 11–16% with respect to MP plans. Overall planning times were dramatically reduced to about 7 and 15 min for Pers plans. Despite the increased complexity, all plans passed the 3%/2 mm γ-analysis for dose verification.ConclusionsThe Personalized engine provided an overall increase of plan quality, in terms of dose conformity and sparing of normal tissues for prostate cancer patients. The Feasibility “a priori” DVH prediction module provided OARs dose sparing well beyond the clinical objectives. The new Pinnacle Personalized algorithms outperformed the currently used Autoplanning ones as solution for treatment planning automation.