Localized Prostate Cancer Research Articles

5-α Reductase Inhibitors and Prostate Cancer Mortality

5-alpha-reductase-inhibitors (5-ARIs) are approved for treating benign prostatic hyperplasia (BPH) and have been found to reduce prostate cancer (PCa) risk by 25%. However, trials also have shown 5-ARIs to be associated with high-grade PCa. Whether 5-ARIs increase mortality among those with a diagnosis of PCa remains unclear. To determine long-term outcomes of clinically localized PCa arising in individuals taking 5-ARIs compared with nonusers. This population-based cohort study was conducted between January 2003 and October 2017. Eligible participants were men aged 65 years or older in Ontario, Canada, who developed clinically localized PCa with complete pathological abstraction from the Ontario Health Administrative Databases. Data analysis occurred from November 2017 to November 2022. 5-ARIs before PCa diagnosis. The primary outcomes were overall mortality and PCa-specific mortality. Cause-specific hazard models with inverse probability treatment weights (IPTW) were used to examine associations of 5-ARI use with mortality outcomes. Sensitivity analyses based on prediagnostic 5-ARI use, Gleason score, comorbidity, 5-ARI indication, prostate-specific antigen modeling, and statin use were also performed. The cohort included 19 938 patients with PCa. Of these, 2112 (10.6%; median [IQR] age, 74 [70-79] years) were 5-ARI users and 17 826 (89.4%; median [IQR] age, 71 [68-76] years) were nonusers. During a median (IQR) follow-up of 8.96 (6.28-12.17) years, 6053 (30.4%) died, including 1047 (5.3%) from PCa. 5-ARI use appeared to be associated with increased overall and PCa specific mortality in crude analyses; however, after IPTW, 5-ARI use was not associated with overall mortality (hazard ratio, 0.98; 95% CI, 0.90-1.07; P = .77) or PCa-specific mortality (hazard ratio, 1.02; 95% CI, 0.83-1.25; P = .84). In this population-based cohort study of 5-ARI use prior to PCa diagnosis including long-term follow-up and clinicopathologic details, prediagnostic 5-ARI use was not associated with PCa-specific or all-cause mortality. This study offers reassuring safety data for patients using 5-ARIs before PCa diagnosis for both BPH and chemopreventive reasons.

Prostate cancer chemotherapy by intratumoral administration of Docetaxel-Mesoporous silica nanomedicines

Docetaxel (DTX) is a recommended treatment in patients with metastasic prostate cancer (PCa), despite its therapeutic efficacy is limited by strong systemic toxicity. However, in localized PCa, intratumoral (IT) administration of DTX could be an alternative to consider that may help to overcome the disadvantages of conventional intravenous (IV) therapy. In this context, we here present the first in vivo preclinical study of PCa therapy with nanomedicines of mesoporous silica nanoparticles (MSN) and DTX by IT injection over a xenograft mouse model bearing human prostate adenocarcinoma tumors. The efficacy and tolerability, the biodistribution and the histopathology after therapy have been investigated for the DTX nanomedicine and the free drug, and compared with the IV administration of DTX. The obtained results demonstrate that IT injection of DTX and DTX nanomedicines allows precise and selective therapy of non-metastatic PCa and minimize systemic diffusion of the drug, showing superior activity than IV route. This allows reducing the therapeutic dose by one order and widens substantially the therapeutic window for this drug. Furthermore, the use of DTX nanomedicines as IT injection promotes strong antitumor efficacy and drug accumulation at the tumor site, improving the results obtained with the free drug by the same route.

Erectile Dysfunction and Penile Bulb Dose Following Definitive Prostate Radiation Therapy

Background: Erectile dysfunction (ED) is a common side effect of prostate cancer treatment, affecting up to 50% of patients after radiation therapy. Objectives: This study aims to analyze the correlation between the dose received by the penile bulb (PB) and ED in men who underwent definitive radiation therapy for early-stage prostate cancer without androgen deprivation therapy. Methods: The study included 40 patients who received 3D conformal radiation therapy (3D-CRT) for localized prostate cancer and were reported to be potent before treatment, as determined by the International Index of Erectile Function (IIEF-15) questionnaire. The dose to the PB was measured using dose volume histograms (DVHs), and the IIEF-15 questionnaire was completed again 3 months after 3D-CRT. The Pearson correlation coefficient and linear regression test were used to examine the correlation between the ED score and PB doses. Statistical significance was considered if the P value was less than 0.05. Results: The mean age of the patients was 75.5 ± 5.70 years. The average ED score based on the questionnaire was 15 ± 10.55. Twenty percent of the patients had moderate ED, while 80% had mild ED (all patients reported a decrease in potency after 3D-CRT). However, the correlation between the ED score and the PB mean dose was not statistically significant. Conclusions: This study revealed ED in all prostate cancer patients after 3D-CRT, but no significant correlation was found between the dose received by the PB and radiotherapy-induced impotence.

Long-term Results of Hypofractionated Radiotherapy With Intra-prostatic Boosts in Men With Intermediate- and High-risk Prostate Cancer: A Phase II Trial

AimsIn the conventionally fractionated phase III FLAME prostate trial, focal boosts improved local control and biochemical disease-free survival (bDFS). We explored the toxicity and effectiveness of a moderately hypofractionated schedule with focal boosts. Material and methodsBIOPROP20 is a phase II single-arm non-randomised trial for intermediate- to very high-risk localised prostate cancer patients with bulky tumour volumes. Multi-parametric magnetic resonance imaging (MRI) and 18F-choline positron emission tomography-computed tomography (PET-CT) scans were used for staging and boost volume definition. Patients were treated with 60Gy in 20 fractions with a boost dose up to 68Gy. Five patients with positive lymph nodes on the PET-CT scan received radiotherapy to pelvic lymph nodes (45Gy to elective nodes, boosted up to 50Gy to involved nodes). Primary outcomes were acute (≤18 weeks) and late urinary and gastrointestinal toxicity, prospectively recorded up to 5 years with Common Terminology Criteria for Adverse Events v4 (CTCAE). Secondary outcomes were biochemical or clinical progression, metastasis-free survival (MFS), and overall survival (OS). Results61 patients completed radiotherapy with hormone therapy (range: 6–36 months). Cumulative acute and late gastrointestinal toxicity was low at 6.6% and 5.0%, respectively. Cumulative acute and late urinary toxicity was 49.2% and 30.1%, respectively; the prevalence reduced to 5.9% at 5 years. At 5 years: 6 patients had biochemical progression (bDFS: 88.5%; 95% CI: 80.2–97.6%), the MFS was 82.4% (95% CI: 73.0–92.9%), 5 patients died (OS: 91.2%; 95% CI: 84.1–98.9%), one with prostate cancer. The prostate, boost, nodal planning volumes, and the organs at risk (rectum, bowel, urethra, and bladder) met the optimal protocol dose constraints. There was a trend to increased urinary toxicity with increasing urethral (RR: 1.95, 95% CI: 0.73–5.22, p = 0.18), but not bladder dose. ConclusionFocal boosts with a 20 fraction hypofractionated prostate radiotherapy schedule are associated with an acceptable risk of gastrointestinal and urinary toxicity and achieve good cancer control. ClinicalTrials.gov identifierNCT02125175.

Outcomes of I-125 Low-Dose-Rate Brachytherapy in Patients with Localized Prostate Cancer: A Comprehensive Analysis from a Specialized Tertiary Referral Center.

Low-dose-rate (LDR) brachytherapy with I-125 seeds is one of the most common primary tumor treatments for low-risk and low-intermediate-risk prostate cancer. This report aimed to present an analysis of single-institution long-term results. We analyzed the treatment outcomes of 119 patients with low- and intermediate-risk prostate cancer treated with LDR brachytherapy at our institution between 2014 and 2020. The analysis focused on biochemical recurrence rates (BRFS), overall survival (OS), cumulative local recurrence rate (CLRR), and the incidence of acute and late toxicities. Patient-reported quality of life measures were also evaluated to provide a holistic view on the treatment's impact. The median follow-up period was 46 months. CLRR was 3.3% (4/119), five-year BRFS was 87%, and the five-year OS rate was 95%. Dysuria was the most common acute urinary toxicity, reported in 26.0% of patients as grade 1 and 13.4% as grade 2. As a late side effect, 12.6% of patients experienced mild dysuria. Sexual dysfunction persisted in 6.7% of patients as grade 1, 7.5% as grade 2, and 10.0% as grade 3. LDR brachytherapy in patients with prostate cancer is an effective treatment, with favorable clinical outcomes and manageable toxicity. The low CLRR and high OS rates, as well as low incidence of severe side effects, support the continued use of LDR brachytherapy as a primary treatment modality for localized prostate cancer.

Focal therapy for prostate cancer.

Traditional treatments for localized prostate cancer include radical prostatectomy or radiation therapy but pose challenges due to treatment related side effects, namely erectile dysfunction and urinary incontinence. In recent years, focal therapy has emerged as a viable treatment option for localized low-intermediate risk prostate cancer in carefully selected patients. Short and medium-term studies show acceptable cancer control outcomes and reduced morbidity when comparing focal therapy to whole gland treatment for prostate cancer, however there is paucity of long-term studies. Here we review focal ablative therapies commonly used, discuss the role of imaging in monitoring treatment, and summarize oncologic outcomes based on studies to date.

Assessing sociodemographic and regional disparities in Oncotype DX Genomic Prostate Score uptake.

The Oncotype DX Genomic Prostate Score (ODX-GPS) is a gene expression assay that predicts disease aggressiveness. The objective of this study was to identify sociodemographic and regional factors associated with ODX-GPS uptake. Data from Surveillance Epidemiology and End Results registries on men with localized prostate cancer with a Gleason score of 3+3 or 3+4, PSA ≤20 ng/mL, and stage T1c to T2c disease from 2013 through 2017 were linked with ODX-GPS data. Census-tract level neighborhood socioeconomic status (nSES) quintiles were constructed using a composite socioeconomic score. Multivariable logistic regression was used to estimate the associations of ODX-GPS uptake with age at diagnosis, race and ethnicity, nSES, geographic region, insurance type, and marital status, accounting for National Comprehensive Cancer Network risk group, year of diagnosis, and clustering by census tract. Among 111,434 eligible men, 5.5% had ODX-GPS test uptake. Of these, 78.3% were non-Hispanic White, 9.6% were Black, 6.7% were Hispanic, and 3.6% were Asian American. Black men had the lowest odds of ODX-GPS uptake (odds ratio, 0.70; 95% confidence interval [CI], 0.63-0.76). Those in the highest versus lowest quintile of nSES were 1.64 times more likely (95% CI, 1.38-2.94) to have ODX-GPS uptake. The odds of ODX-GPS uptake were statistically significantly higher among men residing in the Northeast, West, and Midwest compared to the South. Disparities in ODX-GPS uptake by race, ethnicity, nSES, and geographical region were identified. Concerted efforts should be made to ensure that this clinical test is equitably available.

Clinical decision making in prostate cancer care—evaluation of EAU-guidelines use and novel decision support software

Keeping up to date with the latest clinical advances in prostate cancer can be challenging. We investigated the impact of guideline use on quality of treatment decisions as well as the impact of a novel, CE-certified clinical decision support tool (Siemens AIPC software) on the amount of time clinicians spend on decision-making in a multicenter setting. Ten urologists assessed ten clinical cases (screening and localized prostate cancer) in three settings: without support, using a digital version of the EAU guidelines, and with the AIPC tool, resulting in 300 clinical decisions. Comparison involved time spent, decision correct- and completeness. Using AIPC compared to digital guidelines led to a significant reduction of expenditure of time at a per case level (3.57 min and 0:14 min, p < 0.01) and for overall time per urologist (39.45 min and 02:20 min, p < 0.01). Decision options without guidelines support, online guideline usage and usage of AIPC were complete in 61%, 80% and 100%, respectively (p < 0.01). Decision making without guidelines support, online guideline usage and usage of AIPC was correct including all options in 28%, 66% and 100%, respectively (p < 0.01).Clinical decision support systems have the potential to reduces decision-making time and to enhance decision quality.

Development of deep learning-based novel auto-segmentation for the prostatic urethra on planning CT images for prostate cancer radiotherapy.

Urinary toxicities are one of the serious complications of radiotherapy for prostate cancer, and dose-volume histogram of prostatic urethra has been associated with such toxicities in previous reports. Previous research has focused on estimating the prostatic urethra, which is difficult to delineate in CT images; however, these studies, which are limited in number, mainly focused on cases undergoing brachytherapy uses low-dose-rate sources and do not involve external beam radiation therapy (EBRT). In this study, we aimed to develop a deep learning-based method of determining the position of the prostatic urethra in patients eligible for EBRT. We used contour data from 430 patients with localized prostate cancer. In all cases, a urethral catheter was placed when planning CT to identify the prostatic urethra. We used 2D and 3D U-Net segmentation models. The input images included the bladder and prostate, while the output images focused on the prostatic urethra. The 2D model determined the prostate's position based on results from both coronal and sagittal directions. Evaluation metrics included the average distance between centerlines. The average centerline distances for the 2D and 3D models were 2.07 ± 0.87mm and 2.05 ± 0.92mm, respectively. Increasing the number of cases while maintaining equivalent accuracy as we did in this study suggests the potential for high generalization performance and the feasibility of using deep learning technology for estimating the position of the prostatic urethra.

Pathological Assessment of Men with Grade Group 2 Prostate Cancer.

A variety of treatment options are now available for men with localized prostate cancer (PC); however, there is still debate in determining how and when to intervene for Grade Group (GG) 2 disease. Our study aims to formulate strategies to identify men at risk of upgrading and having adverse pathological outcomes. This retrospective study includes 243 patients with GG2 PC that were treated with radical prostatectomy between 2015 and 2021. Patients on active surveillance, previous history of prostate biopsy, hormonal and/or radiation therapy prior to surgery were excluded from this study. A retrospective analysis was conducted using clinicopathological data obtained from medical records. Prostate-specific antigen (PSA) and Prostate Imaging Reporting and Data System (PI-RADS) score were statistically significant variables for risk of upgrading. In men who had presence of composite poor outcomes, PSA, PI-RADS score, presence of extraprostatic extension and seminal vesical invasion on MRI, number of positive cores, percentage of high grade (pattern 4/5) on prostate biopsy and Gleason pattern 4 volume on biopsy were all statistically significant variables. Strategy 8 (PI-RADS 5 lesion or percentage high grade [Gleason pattern 4] on prostate biopsy grade >10% or >3 cores positive on prostate biopsy) had significant association to identifying the highest number of men with upgrading and composite poor outcomes. Our study supports the use of strategy 8 in treatment decision making of men with GG2 PC. Further validation of the use of this strategy is warranted.

Sociodemographic and clinicopathologic characteristics of patients treated with high dose rate prostate brachytherapy in Nigeria.

Prostate cancer is the most commonly diagnosed malignancy in adult males. High dose rate brachytherapy (HDRB) recently became available in the country for the management of localized prostate cancer in addition to other treatment modalities. HDRB offers a less invasive option to radical prostatectomy and also has a better side effects profile. To report the socio-demographic features of the patients treated with HDRB, the clinicopathologic pattern of their disease and possible predictors of these features. A retrospective study of patients with histopathologically confirmed prostate cancer, who had HDRB at the Department of Radiation Oncology, University College Hospital, Ibadan, Nigeria, between July 2020 and 2023 was done. Patients' socio-demographic and clinicopathologic characteristics were extracted from their treatment records. A total of 73 patients had HDRB within the period under review. The median age was 66 years (51-78 years). About 40% had prostate cancer diagnosed following routine prostate-specific antigen (PSA) screening. The median screening PSA was 20.5 ng/mL (5.83-75.35 ng/mL). About a quarter (24.7%) were asymptomatic at presentation while frequency (60.3%), nocturia (45.2%) and urgency (35.6%) were the most common symptoms. The median initial PSA was 26.00 ng/mL (5.10-124.50 ng/mL) and the median PSA before brachytherapy was 6.25 ng/mL (0.03-175.30 ng/mL), the majority (75.3%) had androgen deprivation therapy before brachytherapy. Forty-seven patients (64.4%) presented with TNM stages 1 and 2 while grade group 2 (24.7%) and high risk (76.7%) were the commonest grade group and risk group, respectively. There was a significant association between age group and TNM stage (p = 0.043), level of education (LOE) and TNM stage (p = 0.037) as well as PSA screening and grade group (p = 0.007). The majority of the patients who presented for prostate brachytherapy were elderly, had higher initial PSA, were in the high-risk group and had early-stage disease. About 25% of the patients were asymptomatic at presentation. Patients with tertiary LOE and elderly patients presented more with stage 1 and 2 diseases.

Detection and management of localized prostate cancer in Nigeria: barriers and facilitators according to patients, caregivers and healthcare providers

BackgroundProstate cancer mortality rates are high in Nigeria. While prostate cancer is highly curable with early detection and effective multidisciplinary management, the quality of care is suboptimal in this setting. Sustainable delivery of high-quality care for patients with localized prostate cancer is needed to save more lives. To inform future interventions to improve care, this study aimed to identify barriers and facilitators that influence prostate cancer detection and management in Nigeria.MethodsSix focus group discussions (FGDs), stratified by stakeholders were conducted with a purposive sample of prostate cancer patients (n = 19), caregivers (n = 15), and healthcare providers (n = 18), in two academic tertiary hospitals in northern and southern Nigeria. A discussion guide organized based on the socio-ecological model was used. FGDs were recorded, transcribed, and analysed using the framework technique.ResultsBarriers and facilitators were identified at the individual, interpersonal, and organizational levels. Barriers to detection included limited knowledge and misperceptions among patients, caregivers, and community-based non-specialist healthcare providers, and limitations of centralized opportunistic screening; while facilitators included the potential for religious institutions to encourage positive health-seeking behaviour. Barriers to management included non-uniformity in clinical guideline usage, treatment abandonment amidst concerns about treatment and survival, absence of patient interaction platforms and follow-up support systems, difficulty in navigating service areas, low health insurance coverage and limited financial resource of patients. Facilitators of management included the availability of resource stratified guidelines for prostate cancer management and the availability of patient peers, caregivers, nurses, and medical social workers to provide correct medical information and support patient-centred services. Participants also provided suggestions that could help improve prostate cancer detection and management in Nigeria.ConclusionThis study identified multiple determinants affecting the detection and management of localized prostate cancer. These findings will inform the refinement of implementation strategies to improve the quality of prostate cancer care in Nigeria.

Delayed definitive management of localized prostate cancer: what do we know?

Delays in the work-up and definitive management of patients with prostate cancer are common, with logistics of additional work-up after initial prostate biopsy, specialist referrals, and psychological reasons being the most common causes of delays. During the COVID-19 pandemic and the subsequent surges, timing of definitive care delivery with surgery or radiotherapy has become a topic of significant concern for patients with prostate cancer and their providers alike. In response, recommendations for the timing of definitive management of prostate cancer with radiotherapy and radical prostatectomy were published but without a detailed rationale for these recommendations. While the COVID-19 pandemic is behind us, patients are always asking the question: "When should I start radiation or undergo surgery?" In the absence of level I evidence specifically addressing this question, we will hereby present a narrative review to summarize the available data on the effect of treatment delays on oncologic outcomes for patients with localized prostate cancer from prospective and retrospective studies.

High-Intensity Focused Ultrasound (HIFU) Treatment for Prostate Cancer

High-Intensity Focused Ultrasound (HIFU) represents an emerging minimally invasive treatment modality for prostate cancer. This technology employs focused ultrasound waves to ablate prostate tissue, offering a precise and targeted strategy for the management of localized prostate cancer. The present paper aims to deliver a comprehensive review of HIFU, encompassing its technology, advantages, risks, patient selection criteria, and post-treatment monitoring.

Neoadjuvant lutetium PSMA, the TIME and immune response in high-risk localized prostate cancer.

High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer.

Tyrosine and tryptophan in urine as biomarkers for prostate cancer: A validation study

Prostate cancer (PCa) is a common male malignancy and early diagnosis is crucial for successful treatment. The current study aims to validate results from a pilot study that demonstrated an inverse association between urine tyrosine and tryptophan levels and the severity of PCa. This study comprised a cohort of 97 patients with benign prostatic hyperplasia, 93 patients diagnosed with localized PCa, 75 patients diagnosed with locally advanced PCa, and 68 patients diagnosed with metastatic PCa. The tyrosine and tryptophan levels in the samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and electrochemical sensors in accordance with the pilot to maintain uniformity for accurately evaluating the data. One-way ANOVA with post Tukey test as well as the Wilcoxon Rank Sum Test were performed. Analyzing 333 patients across PCa stages with consistent methods, we observed no significant differences in tyrosine and tryptophan levels between PCa patients and controls, finally rejecting the use of tyrosine and tryptophan as PCa biomarkers. We did, however, verify the strong correlation between the urinary concentrations of tyrosine and tryptophan found in the pilot study.

Irreversible electroporation of localised prostate cancerdownregulates immune suppression andinduces systemic anti-tumour T-cell activation - IRE-IMMUNO study.

To prospectively compare systemic anti-tumour immune responses induced by irreversible electroporation (IRE) and robot-assisted radical prostatectomy (RARP) in patients with localised intermediate-risk prostate cancer (PCa). Between February 2021 and June 2022, before and after treatment (at 5, 14 and 30 days) peripheral blood samples of 30 patients with localised PCa were prospectively collected. Patient inclusion criteria were: International Society of Urological Pathologists Grade 2-3, clinical cancer stage ≤T2c, prostate-specific antigen level <20 ng/mL). Patients were treated with IRE (n = 20) or RARP (n = 10). Frequency and activation status of lymphocytic and myeloid immune cell subsets were determined using flow cytometry. PCa-specific T-cell responses to prostatic acid phosphatase(PSAP) and cancer testis antigen (New York oesophageal squamous cell carcinoma 1 [NY-ESO-1]) were determined by interferon-γ enzyme-linked immunospot assay (ELISpot). Repeated-measures analysis of variance and two-sided Student's t-tests were used to compare immune responses over time and between treatment cohorts. Patient and tumour characteristics were similar between the cohorts except for age (median 68 years [IRE] and 62 years [RARP], P = 0.01). IRE induced depletion of systemic regulatory Tcells (P = 0.0001) and a simultaneous increase in activated cytotoxic T-lymphocyte antigen 4 (CTLA-4)+ cluster of differentiation (CD)4+ (P < 0.001) and CD8+ (P = 0.032) Tcells, consistent with reduction of systemic immune suppression allowing for effector T-cell activation, peaking 14 days after IRE. Effects were positively correlated with tumour volume/ablation size. Accordingly, IRE induced expansion of PSAP and/or NY-ESO-1 specific T-cell responses in four of the eight immune competent patients. Temporarily increased activated myeloid derived suppressor cell frequencies (P = 0.047) were consistent with transient immunosuppression after RARP. Irreversible electroporation induces a PCa-specific systemic immune response in patients with localised PCa, aiding conversion of the tumour microenvironment into a more immune permissive state. Therapeutic efficacy might be further enhanced by combination with CTLA-4 checkpoint inhibition, potentially opening up a new synergistic treatment paradigm for high-risk localised or (oligo)metastatic disease.

From foes to friends: rethinking the role of lymph nodes in prostate cancer.

Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly 'foes' or whether they are actually 'friends' in oncological care is an important idea to discuss.

Treatment outcome of localized prostate cancer using transperineal ultrasound image-guided radiotherapy

BackgroundWe report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT).MethodsA total of 124 patients (median age: 74 y, 46–84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5–7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76–78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2–3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation.ResultsA total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups.ConclusionThese results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

A practical guide for the use of apalutamide for non-metastatic castration-resistant prostate cancer in Australia.

Studies of patients with castrate-resistant prostate cancer at high risk of developing overt metastases but with no current evidence of evaluable disease on computed tomography or bone scan non-metastatic castrate-resistant prostrate cancer have demonstrated increased metastasis-free survival and overall survival following treatment with the next-generation oral anti-androgen apalutamide (in addition to therapies that aim to lower testosterone to castrate levels) or luteinizing hormone-releasing hormone antagonist or surgical castration. Patients receiving apalutamide can be managed by medical oncologists, radiation oncologists, or urologists, preferably as part of a multidisciplinary team. However, the importance of additional safety monitoring for significant adverse effects and drug interactions should not be underestimated. The toxicities of apalutamide are manageable with experience and should be managed proactively to minimize their impact on patients. Monitoring of patients for apalutamide-specific toxicities, including skin rash, hypothyroidism, and QT prolongation should be carried out regularly, particularly in the first few months following initiation. Monitoring should continue alongside monitoring for toxicities of androgen deprivation, including cardiovascular risk, hot flashes, weight gain, bone health, muscle wasting, and diabetic risk. This review is a practical guide to the use of apalutamide describing the management of patients including dosing and administration, toxicities, potential drug interactions, and safety monitoring requirements.