Male Cancer Research Articles

The Price of Human Evolution: Cancer-Testis Antigens, the Decline in Male Fertility and the Increase in Cancer.

The increasing frequency of general and particularly male cancer coupled with the reduction in male fertility seen worldwide motivated us to seek a potential evolutionary link between these two phenomena, concerning the reproductive transcriptional modules observed in cancer and the expression of cancer-testis antigens (CTA). The phylostratigraphy analysis of the human genome allowed us to link the early evolutionary origin of cancer via the reproductive life cycles of the unicellulars and early multicellulars, potentially driving soma-germ transition, female meiosis, and the parthenogenesis of polyploid giant cancer cells (PGCCs), with the expansion of the CTA multi-families, very late during their evolution. CTA adaptation was aided by retrovirus domestication in the unstable genomes of mammals, for protecting male fertility in stress conditions, particularly that of humans, as compensation for the energy consumption of a large complex brain which also exploited retrotransposition. We found that the early and late evolutionary branches of human cancer are united by the immunity-proto-placental network, which evolved in the Cambrian and shares stress regulators with the finely-tuned sex determination system. We further propose that social stress and endocrine disruption caused by environmental pollution with organic materials, which alter sex determination in male foetuses and further spermatogenesis in adults, bias the development of PGCC-parthenogenetic cancer by default.

Potential roles of NEDD4 and NEDD4L and their utility as therapeutic targets in high‑incidence adult male cancers (Review).

The term 'cancer' refers to >100 disorders that progressively manifest over time and are characterized by uncontrolled cell division. Although malignant growth can occur in virtually any human tissue, the underlying mechanisms underlying all forms of cancer are consistent. The International Agency for Research on Cancer's annual GLOBOCAN 2020 report provided an update on the global cancer incidence and mortality. Excluding non-melanoma skin cancer, the report predicts that there will be 19.3 million new cancer cases and >10 million cancer-related fatalities in 2023. Lung, prostate, and colon cancers are the most prevalent and lethal cancers in males. It was recognized that post-translational modifications (PTMs) of proteins are necessary for almost all cellular biological processes, as well as in cancer development and metastasis to other bodily organs. Thus, PTMs have a considerable impact on how proteins behave. Various PTMs may have harmful roles by affecting the hallmarks of cancer, metabolism and the regulation of the tumor microenvironment. PTMs and genetic changes/mutations are essential in carcinogenesis and cancer development. A pivotal PTM mechanism is protein ubiquitination. Of note, the rate-limiting stage of the protein ubiquitination cascade is hypothesized to be E3-ligase-mediated ubiquitination. Numerous studies revealed that the neural precursor cell expressed developmentally downregulated protein 4 (NEDD4) E3 ligase is among the E3 ubiquitin ligases that have essential roles in cellular processes. It regulates protein degradation and substrate ubiquitination. In addition, it has been shown that NEDD4 primarily functions as an oncogene in various malignancies but can also act as a tumor suppressor in certain types of tumor. In the present review, the roles of NEDD4 as an anticancer protein in various high-incidence male malignancies and the significance of NEDD4 as a potential cancer therapeutic target are discussed. In addition, the targeting of NEDD4 as a therapeutic strategy for the treatment of human malignancies is explored.

Impact of Developing Dialysis-Requiring Acute Kidney Injury on Long-Term Mortality in Cancer Patients with Septic Shock.

(1) Background: Considering recent advances in both cancer and sepsis management, we chose to evaluate the associated factors for occurrence of septic acute kidney injury in cancer patients using a nationwide population-based cohort data. (2) Methods: Using data from the National Health Insurance Service of Korea, adult cancer patients who presented to emergency departments with septic shock from 2009 to 2017 were analyzed. A Cox-proportional hazard model was conducted to evaluate the clinical effect of sepsis-related acute kidney injury requiring dialysis. (3) Results: Among 42,477 adult cancer patients with septic shock, dialysis-requiring acute kidney injury occurred in 5449 (12.8%). Recovery from dialysis within 30 days was 77.9% and, overall, 30-day and 2-year mortality rates were 52.1% and 85.1%, respectively. Oncologic patients with dialysis-requiring acute kidney injury frequently occurred in males and patients with hematologic cancer. A multivariate Cox-proportional hazard model showed that dialysis-requiring acute kidney injury had the highest adjusted hazard ratio of 1.353 (95% confidence interval 1.313-1.395) for 2-year mortality. (4) Conclusions: Dialysis-requiring septic acute kidney injury did not occur commonly. However, it had a significant association with increased long-term mortality, which suggests emphasis should be placed on the prevention of acute kidney injury, particularly in male hematologic cancer patients.

High consumption of pesticides in agricultural fields leads to prevalence of cancer cases in rural pockets of eastern India: A case study

AbstractThis study was performed to evaluate the carcinogenic health risk of pesticides used in agricultural field in rural pockets of eastern India. The analysis of pesticide residue in rice grain sample was performed by Gas Chromatography Mass Spectrometry (GC‐MS). It was observed that for pesticide DDT, the HR values was ranging between 0.5 to 3.2 and for lindane HR was 0.4 to 1.1, respectively. The DDT and Lindane exhibited HR values >1 in some sampling sites which revealed the carcinogenic effects and HR <1 in some sampling sites which revealed non carcinogenic effects of same pesticide. These results revealed a clear indication of potential carcinogenic health risk to human health through consumption of contaminated rice in some areas of Bargarh district. DDT has a long half‐life, so it persists in the environment for a longer period of time and induces carcinogenic risk to human health predominantly than other pesticide lindane. A case study on cancer prevalence in Bargarh district was also carried out to support the findings of quantitative analysis. The primary data collected from the cancer affected area by personal questionnaires method to the person concern and the secondary data collected from the Bargarh District Head Quarters Hospital's register. The cancer death reported by the from the year 2015 to 2021 was 320, 380, 293, 323, 278, 409, 346 in the year of 2015, 2016, 2017, 2018, 2019, 2020, 2021 respectively, with the total number of 2349 cases. From the questionnaire data, it was observed that the occurrence of male and female cancer cases was 51.75% and 48.25%, respectively. Therefore, it was concluded that there was no significant difference in gender wise cancer prevalence. The most affected age group was 51–60, that is, 26.92% followed by 41–50, that is, 23.42%. Therefore, it was concluded that the middle‐aged adults (40–60) were more vulnerable to the cancer than young adults (3–40) and old adults (60–100). The most prevalent cancer was breast (22.72%) followed by stomach (14.33%).

The development and validation of a nomogram for predicting brain metastases after chemotherapy and radiotherapy in male small cell lung cancer patients with stage III.

The purpose of this research was to develop a model for brain metastasis (BM) in limited-stage small cell lung cancer (LS-SCLC) patients and to help in the early identification of high-risk patients and the selection of individualized therapies. Univariate and multivariate logic regression was applied to identify the independent risk factors of BM. A receiver operating curve (ROC) and nomogram for predicting the incidence of BM were then conducted based on the independent risk factors. The decision curve analysis (DCA) was performed to assess the clinical benefit of prediction model. Univariate regression analysis showed that the CCRT, RT dose, PNI, LLR, and dNLR were the significant factors for the incidence of BM. Multivariate analysis showed that CCRT, RT dose, and PNI were independent risk factors of BM and were included in the nomogram model. The ROC curves revealed the area under the ROC (AUC) of the model was 0.764 (95% CI, 0.658-0.869), which was much higher than individual variable alone. The calibration curve revealed favorable consistency between the observed probability and predicted probability for BM in LS-SCLC patients. Finally, the DCA demonstrated that the nomogram provides a satisfactory positive net benefit across the majority of threshold probabilities. In general, we established and verified a nomogram model that combines clinical variables and nutritional index characteristics to predict the incidence of BM in male SCLC patients with stage III. Since the model has high reliability and clinical applicability, it can provide clinicians with theoretical guidance and treatment strategy making.

Breaking the mold: Unveiling male breast cancer through a compelling case study

ABSTRACT Breast cancer in men is rare, it represents <1% of all male cancers, it usually presents between the ages of 60 and 70 years with an age peak at 67 years. Unlike in women, where screening studies are performed, in men, it is usually diagnosed later, because the low incidence of this cancer in male patients and the absence of early signs and symptoms lead to a delayed search for medical attention. Even though more data is emerging about this disease, the poor level of awareness often results in late presentation and delayed diagnosis in our country. The present study reported the case of a 63-year-old man who presented in the outpatient department with a large breast lump and a short history of 2 months; he was diagnosed on fine-needle aspiration cytology with an invasive ductal carcinoma. The case is presented for the rarity and to discuss awareness, regarding early diagnosis, and proper management.

Retrospective study of testosterone deficiency and symptom burden in patients with pancreatic cancer.

Pancreatic cancer patients have poor quality of life. Testosterone deficiency is associated with constitutional symptoms and sexual dysfunction which may contribute to poor quality of life. We investigated the prevalence of screening for and presence of testosterone deficiency in male pancreatic cancer patients. To determine the frequency of screening for testosterone deficiency in pancreatic cancer patients, our institution's electronic medical record system was queried for male patients diagnosed with a pancreatic mass between 2006 and 2020 and an available testosterone level. In a separate analysis, total testosterone was measured in serum samples from a cohort of 89 male pancreatic ductal adenocarcinoma (PDAC) patients. Low serum testosterone was defined as <300 ng/dL. One thousand five hundred and sixty-six male patients were identified with a pancreatic mass, and 35 (2.2%) also had a testosterone level. In our analysis cohort, 44 of 89 patients (49.4%) were found to have low serum testosterone. Symptoms consistent with testosterone deficiency were documented for 70% of these patients, with fatigue being the most common. Testosterone level had no significant association with progression-free survival (PFS) (P=0.66) or overall survival (OS) (P=0.95). Testosterone deficiency is common but rarely assessed in male patients with pancreatic cancer. Further studies are warranted to explore the possibility of testosterone supplementation to improve quality of life in this patient population.

Attenuation of doxorubicin-induced hypothalamic-pituitary-testicular axis dysfunction by diphenyl diselenide involves suppression of hormonal deficits, oxido-inflammatory stress and caspase 3 activity in rats

BackgroundDoxorubicin (DOX) is one of the popular anti-cancer drugs in the world and several literatures have implicated it in various toxicities especially cardiotoxicity and reproductive toxicity. Diphenyl diselenide (DPDS) is well acknowledged for its compelling pharmacological effects in numerous disease models and chemically-mediated toxicity. This study was carried out to investigate the effect of DPDS on DOX-induced changes in the reproductive indices of male Wistar rats. MethodsRats were intraperitoneally injected with 7.5 mg/kg body weight of DOX alone once followed by treatment with DPDS at 5 and 10 mg/kg for seven successive days. Excised hypothalamus, testes and epididymis were processed for biochemical and histological analyses. ResultsDPDS treatment significantly (p < 0.05) abated DOX-induced oxidative damage by decreasing the levels of oxidative stress indices such as hydrogen peroxide, reactive oxygen and nitrogen species, and lipid peroxidation with a respective improvement in the level of glutathione in the hypothalamic, testicular and epididymal tissues of DOX-treated rats. The activities of antioxidant enzymes such as catalase, superoxide dismutase, glutathione S-transferase and glutathione peroxidase were upregulated in the DPDS co-treated group. DPDS co-treatment alleviates the burden of DOX-induced inflammation by significant reductions in myeloperoxidase activity, levels of nitric oxide and tumor necrosis factor alpha with concomitant decline in the activity of caspase-3, an apoptotic biomarker. Consequently, significant improvement in the spermiogram, levels of reproductive hormones (follicle stimulating hormone, luteinizing hormone, prolactin, serum testosterone and intra-testicular testosterone) levels in the DPDS co-treatment group in comparison to DOX alone-treated group were observed. Histology results of the testes and epididymis showed that DPDS significantly alleviated pathological lesions induced by DOX in the animals. ConclusionDPDS may modulate reproductive toxicity associated with DOX therapy in male cancer patients.

HSF1 is a novel prognostic biomarker in high-risk prostate cancer that correlates with ferroptosis

BackgroundProstate cancer (PC) is the most common cancer in older men in Europe and the United States and has the second highest death rate among male cancers. The transcription of heat shock proteins by Heat shock factor 1 (HSF1) is known to regulate cell growth and stress. Nevertheless, the impact of HSF1 on ferroptosis in PC through heat shock protein 10 (HSPE1) remains unexplored.MethodsThis study employed a range of analytical techniques, including proteomics sequencing, LC–MS/MS, CHIP-qPCR, Western blotting, immunohisto -chemistry, JC-1, CKK-8, MDA, and ROS assays. Bioinformatics analysis was performed using the UALCAN,GEPIA, PCaDB and Metascape platforms.ResultsCompared with levels observed in tumor-adjacent tissue, the levels of proteins associated with fatty acids, amino acids and the oxidative phosphorylation metabolic pathway were significantly upregulated in high-risk PC tissue (Gleason score ≥ 8). HSF1 mRNA and protein levels in high-risk PC tissues were significantly higher than those observed in medium-risk PC (Gleason score = 7) and low-risk PC (Gleason score ≤ 6) tissues. ssGSEA showed that HSF1 was involved in the proliferation and anti-apoptotic processes of PC. Further bioinformatics analysis showed that HSF1 potentially affects the mitochondrial oxidative phosphorylation (OXPHOS) system by targeting HSPE1. In addition, HSF1 alleviates ROS and MDA levels to enhance the resistance of prostate cancer cells to ferroptosis by regulating HSPE1 in vitro, and HSF1 knockout promotes the susceptibility of PC to RSL3 treatment by increasing ferroptosis in vivo.ConclusionCollectively, our findings suggest that HSF1 exerts a significant influence on PC. HSF1 may represent a promising biomarker for identifying high-risk PC, and the elimination of HSF1 could potentially enhance the therapeutic effectiveness of RSL3.

P-051 Male cancer patient sperm cryopreservation for fertility preservation: 11-year multicenter experience: 16 regions of the mainland China national sperm

Abstract Study question What is the current status of fertility preservation (FP) of male cancer utilization, efficacy and safety in China and what national trends could be observed? Summary answer In this national report on FP status of male cancer over a 11-year period, data on population and trends, region development of FP are analyzed. What is known already Cryopreservation of sperm, the current standard option to preserve male patient's fertility, is very advantageous for men suffering from cancer. Unfortunately, the data on population and trends, region development of fertility preservation (FP)of male cancer in mainland China is scarce. Study design, size, duration A multicenter retrospective study of male cancer patients who performed sperm cryopreservation from 16 regions of a national network of sperm banks over a 11-year period from 2010 to 2020. A total of 2270 men with cancer were referred to 16 human sperm banks for fertility preservation. Participants/materials, setting, methods This national survey was conducted through 16 provincial administrative sectors to sperm cryopreservation for Chinese male cancer. Sperm cryopreservation for male cancer is conducted in 16 human sperm banks, which done well in Sperm cryopreservation for male cancer. Cancer diagnoses were classified according to types, as Testicular tumors, Lymphomas, Leukemia, Colorectal tumors, Nasopharyngeal carcinomas, Sarcomas, Brain tumors, Extragonadal germ cell tumors, and with other cancers grouped together. Main results and the role of chance The number of male cancer patients with sperm cryopreservation showed an overall upward trend. Statistically significant mean yearly increases were observed for three most frequent types of cancer (testicular cancers, lymphoma, leukemia). The development of male cancer FP in the eastern, central, and western regions of Chinese mainland displayed imbalance. There are seven tumor types for sperm preservation in the top incidence ten tumor types, including lymphoma, leukemia, nasopharyngeal carcinoma, sarcoma, thyroid cancer and brain tumor. Moreover, nasopharyngeal carcinoma is a high incidence rate in China, which is related to high sperm preservation rate, different from others countries. The most percentage of males receiving sperm cryopreservation in the testicular cancers (15-39 years old) of China in 2020 was 5.55%, 1.29% in the lymphoma and 0.39% in the Leukemia. According to type of cancer, a statistically significant lower pre-sperm density, total sperm output and post-sperm density was observed in Testicular cancers. It's worth noting that the prevalence of azoospermia 22.2 % in Leukemia patients. Disposition of cryopreserved sperm categories included continued storage (47.2%), discarded (9%), death (0.9%), and use (3.7%). Up to 2020, 70 patients (3.7%) who underwent assisted reproductive technology (ART) used their cryopreserved semen. Limitations, reasons for caution The limitations of our study are the inability to follow-up couples who were naturally conceived. Another limitation is that not all clinical outcomes have been gated. Wider implications of the findings This study provides the most comprehensive national statistical census and review of fertility preservation in men cancer patients trends, quantity and cancer types. Our findings regarding patients’ characteristics and analysis of semen parameters and sperm usage rate. Trial registration number not applicable

Social inequalities in male cancer in a metropolis in the Southeast region of Brazil.

To analyze inequalities in incidence, mortality, and estimated survival for neoplasms in men according to social vulnerability. Analysis of cases and deaths of all neoplasms and the five most common in men aged 30 years or older in the city of Campinas (SP), between 2010 and 2014, using data from the Population-Based Cancer Registry (RCBP) and the Mortality Information System (SIM). The areas of residence were grouped into five social vulnerability strata (SVS) using São Paulo Social Vulnerability Index. For each SVS, age-standardized incidence and mortality rates were calculated. A five-year survival proxy was calculated by complementing the ratio of the mortality rate to the incidence rate. Inequalities between strata were measured by the ratios between rates, the relative inequality index (RII) and the angular inequality index (AII). RII revealed that the incidence of all neoplasms (0.66, 95%CI 0.62-0.69) and colorectal and lung cancers were lower among the most socially vulnerable, who presented a higher incidence of stomach and oral cavity cancer. Mortality rates for stomach, oral cavity, prostate and all types of cancer were higher in the most vulnerable segments, with no differences in mortality for colorectal and lung cancer. Survival was lower in the most social vulnerable stratum for all types of cancer studied. AII showed excess cases in the least vulnerable and deaths in the most vulnerable. Social inequalities were different depending on the tumor location and the indicator analyzed. There is a trend of reversal of inequalities between incidence-mortality and incidence-survival, and the most social vulnerable segment presents lower survival rates for the types of cancer, pointing to the existence of inequality in access to early diagnosis and effective and timely treatment.

P-064 MicroRNAs as potential biomarkers for male infertility related to Testicular Germ Cell Tumors

Abstract Study question Could microRNAs represent efficient biomarkers to evaluate male infertility and the tendency of develop testicular germ cell tumors (TGCTs)? Summary answer The up-regulation of miR-193a-5p, miR-93-5p and let-7c-5p in TGCT patients with impaired spermiogram could represent a molecular signature of male infertility related to TGCTs. What is known already Testicular germ cell tumors (TGCTs) are the most recurrent tumors in young men with the highest incidence between the ages of 20 and 40 years and represent more than 60% of all cancers diagnosed in this age range. Several studies have shown a correlation between TGCTs and infertility, not only because infertility could be a consequence of testicular damage due to TGCTs but also because infertility may represent a risk factor for TGCTs. Therefore, it is important to find valid biomarkers that could be used to specifically identify infertility related to an increased risk of developing TGCTs. Study design, size, duration From March 2021 to January 2023, we collected 44 seminal plasma samples: 17 from TGCT patients who were undergoing sperm cryopreservation prior to chemotherapy, 14 with impaired spermiogram (IS) and 3 with normal spermiogram (NS) and 27 from control patients, 16 with IS and 11 with NS, undergoing assisted fertilization techniques. We evaluated the potential role of miRNAs as non-invasive biomarkers, analyzing the differential expression of 84 miRNAs in relation to cancer, infertility and both. Participants/materials, setting, methods Semen samples were placed 30’/37 °C, seminal plasma was purified using density-gradient centrifugation and stored at -80 °C. RNA was purified by Qiagen miRNeasy Serum/Plasma Kit and analyzed by miRCURY LNA miRNA SYBR®Green PCR_SerumPlasma, 96-well plate. We applied the 2−ΔΔCT method and statistical significance was evaluated by Significance Analysis of Microarrays, screened by p-values ≤ 0.05. We performed a Pearson correlation analysis applying two-sided p-values. miRTarBASE, MIENTURNET and Cytoscape were used for bioinformatics analysis. Main results and the role of chance In the four comparisons, we found 9 differentially expressed microRNAs. In particular, miR-221-3p, miR-222-3p, miR-204-5p and miR-205-5p down regulation would appear to be related to infertility, regardless to the cancer. Conversely, all TGCT patients shown an up-regulation of miR-376c-3p. Interestingly, up-regulation of miR-193a-5p, miR-93-5p and let-7c-5p specifically discriminates the infertile cancer patients vs other categories. Moreover, these three miRNAs showed a significant positive correlation both in cancer patients with impaired spermiogram and in infertile controls. This correlation demonstrates that their expression changes in the same way in the single samples and strongly suggests their role as early biomarkers of TGCT patients with impaired spermiogram. From the KEGG pathway analysis has emerged that DE miRNAs are involved in several signaling pathway, such as MAPK, mTOR, p53, PI3K-Akt, AMPK, FoxO, JAK-STAT, Ras, Estrogen signaling pathways, as well as cell cycle and cellular senescence. Moreover, from the Diseases Ontology analysis we found than those miRNAs are involved in germ cell tumor, male reproductive organ cancer, prostate cancer, male infertility and azoospermia. Limitations, reasons for caution The data must be validated by single assays in higher number of samples. These experiments are currently ongoing. Wider implications of the findings Three of the DE miRNAs are overexpressed in TGCT with impaired spermiogram patients. Specifically, they are over-expressed in TGCT with impaired spermiogram compared to infertile controls, so they may represent specific biomarkers able to discriminate, among the young men with infertility, those with higher risk of develop testicular cancer. Trial registration number Not applicable

P-401 Is cancer type associated with semen quality and infertility among men who desire fertility preservation?

Abstract Study question To investigate the association between cancer-types and semen-parameters before gonadotoxic-treatments, and to evaluate which patients have the highest risk of diminished spermatogenesis prior to therapy. Summary answer sperm quality among cancer patients before gonadotoxic treatment can differ according to the type of cancer. What is known already Many studies have reported impaired sperm quality at cancer diagnosis before any given gonadotoxic regiments. Except for testicular cancer and Hodgkin’s Lymphoma, baseline data on semen quality in case of different types of malignancies among male cancer patients are limited or based on low sample size Study design, size, duration A retrospective population-based cohort analysis was performed, 237 oncological male patients who were referred for fertility preservation between 1995-2020 within 90 days of cancer diagnosis and prior to cancer treatment Participants/materials, setting, methods The study population included 237oncological male patients who were referred to the Sperm Bank, Fertility, and IVF unit for the purpose of fertility preservation. Sperm analysis was performed within 90 days of cancer diagnosis and prior to therapy. The pre-treatment sperm analyses were based on the World Health Organization (WHO) guidelines Main results and the role of chance Histological examination of malignant diseases demonstrated 20 subtypes of cancers, the major groups included 49 patients with testicular cancer (TC), 72 patients with Hodgkin lymphoma (HD), 35 patients with other lymphoma, 29 patients with other hematological cancer, 16 with sarcoma and 36 with other solid malignant tumors. Our results show significant difference in sperm concentration between the different cancer groups (P value 0.007), the lowest median concentration of spermatozoa was found in the testicular cancer and sarcoma cancer patients 10 million per ml compared to the other cancer groups (other hematologic, Hodgkin lymphoma, other lymphoma and other solid tumors). Oligospermia was observed in 59% of testicular cancer patients and 50% of the sarcoma patients. Fertility outcomes were analyzed as a secondary objective. We found that only 37 patients' partners conceived and delivered offspring. Only 16.2% of those patients used their banked sperm and conceived via IVF-ICSI. We found that 20% of testicular cancer patients and other lymphoma patients including NHL conceived spontaneously after cancer diagnosis and treatment. Limitations, reasons for caution This is a retrospective cohort study and the oncology patients sample size is relatively small. Wider implications of the findings Our study emphasizes that sperm quality among cancer-patients before gonadotoxic-treatment can differ according to the cancer type. Significant reduction in sperm quality in testicular cancer patients was demonstrated, with a significant association was found between sperm concentration and various cancer-type. Further studies are warranted to confirm our results. Trial registration number not applicable

Changes in the Histology of Lung Cancer in Northern Italy: Impact on Incidence and Mortality

This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of −3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (−12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study’s findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence.

Epidemiology of laryngeal cancer in Brazil: Historical data from 2000 to 2019

IntroductionTo determine the incidence, morbidity, and mortality rate of laryngeal cancer in two decades and its epidemiological, clinical, and histological characteristics by sex in Brazil. MethodsThis ecological study used three reliable sources of secondary data: population- and hospital-based cancer registries and the national mortality database. All data available from 2000 to 2019 were considered. ResultsThe incidence of male laryngeal cancer decreased from 9.20 to 4.95 per 100,000 from 2000 to 2018, while mortality slightly decreased from 3.37 to 3.30 per 100,000 from 2000 to 2019. In the same period, the female incidence decreased from 1.26 to 0.48 per 100,000; however, mortality slightly increased from 0.34 to 0.36 per 100,000. Of 221,566 individuals with head and neck cancer, 27 % presented laryngeal cancer. The median age was 61 years (54−69), and most individuals were male (86.6 %), smokers (66.2 %), diagnosed with locally advanced cancer (66.7 %), and squamous cell carcinoma as the main histological type (93.2 %). Male tended to be older (p < 0.001), white (p < 0.001), smokers (p < 0.001), and present late treatment initiation (p < 0.001) and early death (p < 0.001) compared with female. ConclusionThe male laryngeal cancer affected mainly at productive age but with a decreased incidence, probably due to a reduction in smoking habit. However, mortality did not change, which may be explained by the late diagnosis and lack of access to radiotherapy.

Intra-prostatic gold fiducial marker insertion for image-guided radiotherapy (IGRT): five-year experience on 795 patients

IntroductionProstate cancer is the second most commonly diagnosed cancer in males. The use of intra-prostatic fiducial markers (FM) for image-guided radiotherapy (IGRT) has become widespread due to their accuracy, relatively safe use, low cost, and reproducibility. FM provides a tool to monitor prostate position and volume changes. Many studies reported low to moderate rates of complications following FM implantation. In the current study, we present our five years’ experience regarding the insertion technique, technical success, and rates of complication and migration of intraprostatic insertion of FM gold marker.MethodsFrom January 2018 to January 2023, 795 patients with prostate cancer candidate for IGRT (with or without a history of radical prostatectomy) enrolled in this study. We used three fiducial markers (3*0.6 mm) inserted through an 18-gauge Chiba needle under transrectal ultrasonography (TRUS) guidance. The patients were observed for complications up to seven days after the procedure. Besides, the rate of marker migration was recorded.ResultsAll procedures were completed successfully, and all patients tolerated the procedure well with minimal discomfort. The rate of sepsis after the procedure was 1%, and transient urinary obstruction was 1.6%. Only two patients experienced marker migration shortly after insertion, and no fiducial migration was reported throughout radiotherapy. No other major complication was recorded.DiscussionTRUS-guided intraprostatic FM implantation is technically feasible, safe, and well-tolerated in most patients. The FM migration can seldom occur, with negligible effects. This study can provide convincing evidence that TRUS-guided intra-prostatic FM insertion is an appropriate choice for IGRT.

Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices.

Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years. This fostered the search for alternative strategies, independent of the androgen receptor signaling pathway. In this line, radionuclide therapies may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases with the use of radiopharmaceuticals containing samarium-153, strontium-89 or radium-223 or tumor cells expressing the prostate-specific membrane antigen (PSMA), a protein found at the surface of prostate cancer cells. This review gives highlights the chemical properties of radioligands targeting prostate cancer cells and recapitulates the clinical trials evaluating the efficacy of radionuclide therapies, alone or in combination with other approved treatments, in patients with castration-resistant prostate tumors. It discusses some of the encouraging results obtained, especially the benefit on overall survival that was reported with [177Lu]-PSMA-617. It also addresses the specific requirements for the use of this particular class of drugs, both in terms of medical staff coordination and adapted infrastructures for efficient radioprotection.

Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review.

Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.

Breast cancer: the first comparative evaluation of oncobiome composition between males and females

BackgroundEmerging evidence suggests that breast microbiota dysbiosis contributes to cancer initiation, progression, prognosis and treatment efficacy. Anyway, available data are referred only to female patients, and studies on males are completely missing. Male breast cancer (MBC) is 70–100 times less frequent, but the mortality rate adjusted to incidence is higher in men than in females. Currently, MBC diagnostic approaches and treatments have generally been extrapolated from the clinical experience gained in women, while few studies focus on characterizing male cancer biology. Taking into account the rising importance of the oncobiome field and the need of MBC targeted studies, we explored the breast cancer oncobiome of male and female patients.Methods16S rRNA gene sequencing was performed in 20 tumor and 20 non-pathological adjacent FFPE breast tissues from male and female patients.ResultsWe documented, for the first time, the presence of a sexually dimorphic breast-associated microbiota, here defined as “breast microgenderome”. Moreover, the paired analysis of tumor and non-pathological adjacent tissues suggests the presence of a cancer-associated dysbiosis in male patients, with surrounding tissue conserving a healthier microbiome, whereas in female patients, the entire breast tissue is predisposed to cancer development. Finally, the phylum Tenericutes, especially the genera Mesoplasma and Mycobacterium, could to be involved in breast carcinogenesis, in both sexes, deserving further investigation, not only for its role in cancer development but even as potential prognostic biomarker.ConclusionsBreast microbiota characterization can enhance the understanding of male breast cancer pathogenesis, being useful for detection of new prognostic biomarkers and development of innovative personalized therapies, remarking the relevant gender differences.

Abstract A080: Male-biased metabolic and structural muscular changes driven by testosterone flare-like conditions

Abstract Background: During the first 1 to 3 weeks of LHRH-agonist therapy for recurrent or metastatic prostate cancer, an initial increase in testosterone is associated with a condition known as "flare." Flare often is accompanied by fatigue, increases in immune infiltrate in prostate cancer and cardiovascular distress. Cardiovascular myopathies and fatigue have been associated with chronic inflammatory responses and activated cell-mediated immunity. Methods and Results: Using a model of autoimmune mice with persistent low-level expression of proinflammatory interferon gamma (IFN-g), we found fatigue and aberrant cardiovascular activity in the form of reduced ejection fraction responding to exercise in male but not female mice. This finding suggests that male hormone has a potential role for impacting cardiovascular fatigue with a more activated immune environment. Furthermore, analysis of cardiovascular tissues revealed an increase in factors associated with fatigue, such as lactic acid production and changes in expression of genes associated with an increase in anaerobic respiration and poor mitochondrial performance in cardiac musculature. Conclusion: These results indicate that the chronic expression of IFN-g may be synergetic with androgen to produce a male-biased fatigue and muscle dysfunction. Considering that the most frequent side effects to activated immune therapies to cancer in males undergoing CAR-T therapies are fatigue and cardiomyopathies we believe this insight may be beneficial to patients of other therapies as well. Understanding the biological effects of therapy driven flare may offer opportunities for physiological interventions in patients undergoing persistent or intermittent LHRHa therapy. Citation Format: John M. Fenimore, Danielle Springer, Elijah Edmonston, Kunio Nagashima, Adam Sowalsky, Howard Young. Male-biased metabolic and structural muscular changes driven by testosterone flare-like conditions [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A080.