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European Urology Jul 2023Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer...
BACKGROUND
Previous studies have reported on incidence and mortality patterns for individual genitourinary cancers in the USA. However, these studies addressed individual cancer types rather than genitourinary cancers overall.
OBJECTIVE
To comprehensively examine disparities and trends in the incidence and mortality for the four major genitourinary cancers (bladder, kidney, prostate, and testis) in the USA.
DESIGN, SETTING, AND PARTICIPANTS
We obtained incidence data from the National Cancer Institute 22-registry Surveillance, Epidemiology and End Results (SEER) database and the US Cancer Statistics database (Centers for Disease Control and Prevention) and mortality data from the National Center for Health Statistics to examine cross-sectional and temporal trends in incidence and death rates stratified by sex, race/ethnicity, and county.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Age-adjusted incidence and death rates were calculated using SEER*Stat software. Temporal trends were analyzed using Joinpoint regression for a two-sided significance level of p < 0.05.
RESULTS AND LIMITATIONS
Incidence and mortality rates for bladder and kidney cancers were two to four times higher for men than for women. Among non-Hispanic White individuals, the highest incidence rates were found in the Northeast for bladder cancer and in Appalachia for kidney cancer, whereas the highest death rates for prostate cancer were found in the West. Incidence rates increased for cancers of the kidney and testis and for advanced-stage prostate cancer in almost all racial/ethnic populations and for bladder cancer in the American Indian/Alaska Native population. Death rates increased for testicular cancer in the Hispanic population and stabilized for prostate cancer among White and Asian American/Pacific Islander men after a steady decline since the early 1990s. Study limitations include misclassification of race/ethnicity on medical records and death certificates.
CONCLUSIONS
We found persistent sociodemographic disparities and unfavorable trends in incidence or mortality for all four major genitourinary cancers. Future studies should elucidate the reasons for these patterns.
PATIENT SUMMARY
In the USA, rates of cancer cases are increasing for kidney, testis, and advanced-stage prostate cancers in the overall population, and for bladder cancer in the American Indian/Alaska Native population. Differences in the rates by sex and race/ethnicity remain.
Topics: Male; Humans; United States; Testicular Neoplasms; Incidence; Cross-Sectional Studies; Prostatic Neoplasms; Kidney Neoplasms; Urinary Bladder Neoplasms; SEER Program
PubMed: 36566154
DOI: 10.1016/j.eururo.2022.11.023 -
The Lancet. Oncology Jun 2023It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer... (Review)
Review
BACKGROUND
It is proposed that, through restriction to individuals delineated as high risk, polygenic risk scores (PRSs) might enable more efficient targeting of existing cancer screening programmes and enable extension into new age ranges and disease types. To address this proposition, we present an overview of the performance of PRS tools (ie, models and sets of single nucleotide polymorphisms) alongside harms and benefits of PRS-stratified cancer screening for eight example cancers (breast, prostate, colorectal, pancreas, ovary, kidney, lung, and testicular cancer).
METHODS
For this modelling analysis, we used age-stratified cancer incidences for the UK population from the National Cancer Registration Dataset (2016-18) and published estimates of the area under the receiver operating characteristic curve for current, future, and optimised PRS for each of the eight cancer types. For each of five PRS-defined high-risk quantiles (ie, the top 50%, 20%, 10%, 5%, and 1%) and according to each of the three PRS tools (ie, current, future, and optimised) for the eight cancers, we calculated the relative proportion of cancers arising, the odds ratios of a cancer arising compared with the UK population average, and the lifetime cancer risk. We examined maximal attainable rates of cancer detection by age stratum from combining PRS-based stratification with cancer screening tools and modelled the maximal impact on cancer-specific survival of hypothetical new UK programmes of PRS-stratified screening.
FINDINGS
The PRS-defined high-risk quintile (20%) of the population was estimated to capture 37% of breast cancer cases, 46% of prostate cancer cases, 34% of colorectal cancer cases, 29% of pancreatic cancer cases, 26% of ovarian cancer cases, 22% of renal cancer cases, 26% of lung cancer cases, and 47% of testicular cancer cases. Extending UK screening programmes to a PRS-defined high-risk quintile including people aged 40-49 years for breast cancer, 50-59 years for colorectal cancer, and 60-69 years for prostate cancer has the potential to avert, respectively, a maximum of 102, 188, and 158 deaths annually. Unstratified screening of the full population aged 48-49 years for breast cancer, 58-59 years for colorectal cancer, and 68-69 years for prostate cancer would use equivalent resources and avert, respectively, an estimated maximum of 80, 155, and 95 deaths annually. These maximal modelled numbers will be substantially attenuated by incomplete population uptake of PRS profiling and cancer screening, interval cancers, non-European ancestry, and other factors.
INTERPRETATION
Under favourable assumptions, our modelling suggests modest potential efficiency gain in cancer case detection and deaths averted for hypothetical new PRS-stratified screening programmes for breast, prostate, and colorectal cancer. Restriction of screening to high-risk quantiles means many or most incident cancers will arise in those assigned as being low-risk. To quantify real-world clinical impact, costs, and harms, UK-specific cluster-randomised trials are required.
FUNDING
The Wellcome Trust.
Topics: Male; Humans; Testicular Neoplasms; Early Detection of Cancer; Risk Factors; Breast Neoplasms; Prostatic Neoplasms; Colorectal Neoplasms; United Kingdom; Genetic Predisposition to Disease
PubMed: 37178708
DOI: 10.1016/S1470-2045(23)00156-0 -
Deutsches Arzteblatt International Dec 2023Germ-cell tumors of the testes are the most common type of malignant tumor in men aged 20 to 40. Their incidence in Germany is 10 per 100 000 men per year, with an... (Review)
Review
BACKGROUND
Germ-cell tumors of the testes are the most common type of malignant tumor in men aged 20 to 40. Their incidence in Germany is 10 per 100 000 men per year, with an estimated 4200 new cases annually.
METHODS
This selective review is based on the recommendations of the German clinical practice guideline on the diagnosis, treatment and follow-up care of testicular germ-cell tumors, as well as on pertinent original articles and reviews.
RESULTS
The treatment of germ-cell tumors requires an interdisciplinary approach comprising resection of the affected testis followed by further steps that depend on the histological type and stage of the tumor, which may include active surveillance, chemotherapy, radiotherapy, further surgery, or some combination of these measures. Two-thirds of germ-cell tumors are diagnosed in clinical stage I, when they are still confined to the testis; one-third are already metastatic when diagnosed, with organ metastases in 10-15%. Stage-based multimodal treatment approaches are associated with cure rates of more than 99% for stage I tumors and 67-95% for advanced metastatic disease, depending on the degree of progression.
CONCLUSION
For patients with early-stage tumors, overtreatment should be avoided in order to minimize long-term sequelae. For those whose tumors are in advanced stages, it must be decided which patients should receive intensified treatment to optimize the outcome. Multimodal treatment approaches are associated with high cure rates even for patients with metastatic disease.
Topics: Male; Humans; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Combined Modality Therapy; Germany; Disease Progression
PubMed: 37378600
DOI: 10.3238/arztebl.m2023.0143 -
Nature Communications May 2023How the genetic landscape governs a tumor's response to immunotherapy remains poorly understood. To assess the immune-modulatory capabilities of 573 genes associated...
How the genetic landscape governs a tumor's response to immunotherapy remains poorly understood. To assess the immune-modulatory capabilities of 573 genes associated with altered cytotoxicity in human cancers, here we perform CRISPR/Cas9 screens directly in mouse lung cancer models. We recover the known immune evasion factors Stat1 and Serpinb9 and identify the cancer testis antigen Adam2 as an immune modulator, whose expression is induced by Kras and further elevated by immunotherapy. Using loss- and gain-of-function experiments, we show that ADAM2 functions as an oncogene by restraining interferon and TNF cytokine signaling causing reduced presentation of tumor-associated antigens. ADAM2 also restricts expression of the immune checkpoint inhibitors PDL1, LAG3, TIGIT and TIM3 in the tumor microenvironment, which might explain why ex vivo expanded and adoptively transferred cytotoxic T-cells show enhanced cytotoxic efficacy in ADAM2 overexpressing tumors. Together, direct in vivo CRISPR/Cas9 screens can uncover genetic alterations that control responses to immunotherapies.
Topics: Animals; Humans; Male; Mice; Antigens, Neoplasm; Antineoplastic Agents; Fertilins; Immunotherapy; Lung Neoplasms; Membrane Proteins; Serpins; T-Lymphocytes, Cytotoxic; Tumor Microenvironment
PubMed: 37258521
DOI: 10.1038/s41467-023-38841-7 -
Frontiers in Endocrinology 2024Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most... (Review)
Review
Cryptorchidism is the condition in which one or both testes have not descended adequately into the scrotum. The congenital form of cryptorchidism is one of the most prevalent urogenital anomalies in male newborns. In the acquired form of cryptorchidism, the testis that was previously descended normally is no longer located in the scrotum. Cryptorchidism is associated with an increased risk of infertility and testicular germ cell tumors. However, data on pubertal progression are less well-established because of the limited number of studies. Here, we aim to review the currently available data on pubertal development in boys with a history of non-syndromic cryptorchidism-both congenital and acquired cryptorchidism. The review is focused on the timing of puberty, physical changes, testicular growth, and endocrine development during puberty. The available evidence demonstrated that the timing of the onset of puberty in boys with a history of congenital cryptorchidism does not differ from that of non-cryptorchid boys. Hypothalamic-pituitary-gonadal hormone measurements showed an impaired function or fewer Sertoli cells and/or germ cells among boys with a history of cryptorchidism, particularly with a history of bilateral cryptorchidism treated with orchiopexy. Leydig cell function is generally not affected in boys with a history of cryptorchidism. Data on pubertal development among boys with acquired cryptorchidism are lacking; therefore, more research is needed to investigate pubertal progression among such boys.
Topics: Infant, Newborn; Humans; Male; Cryptorchidism; Testicular Neoplasms; Leydig Cells; Puberty
PubMed: 38532895
DOI: 10.3389/fendo.2024.1347435 -
Ugeskrift For Laeger Jan 2024Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumour and a cause of hydrocele. This case report concerns a 26-year-old male with hydrocele treated with...
Mesothelioma of the tunica vaginalis testis (MTVT) is a rare tumour and a cause of hydrocele. This case report concerns a 26-year-old male with hydrocele treated with left hydrocelectomy. Histopathology revealed MTVT, and left radical orchiectomy was performed followed by chemotherapy. Fluorescence in situ hybridization, DNA and RNA next-generation sequencing showed no mesothelioma-associated tumour suppressor gene mutations, but deletion of CDKN2A and a rare TFG-ADGRG7 fusion both reported in pleural mesotheliomas, were detected. Clinicians should consider malignancy in case of discrepancy between symptoms and objective findings in scrotal conditions.
Topics: Male; Humans; Adult; Testis; In Situ Hybridization, Fluorescence; Testicular Neoplasms; Mesothelioma; Mesothelioma, Malignant; Testicular Hydrocele
PubMed: 38305267
DOI: 10.61409/V07230476 -
International Journal of Gynaecology... Dec 2023Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if...
Fertility preservation is a growing field in reproductive medicine that may raise ethical questions. Preservation of fertility must be discussed with the patient if gonadotoxic treatment is required, whether in the case of benign or malignant pathology, or in the management of transgender identity. As a result, surgery or chemotherapy that has fewer adverse impacts on fertility should be proposed if this does not alter the prognosis of the disease. If the risk of infertility persists, then fertility cryopreservation should be proposed for children and adults of reproductive age. Sperm, oocytes, and gonadal tissue can be cryopreserved for many years. FIGO wishes to emphasize the importance of fertility preservation in the medical and surgical management of patients, and the importance of a specialized, multidisciplinary approach.
Topics: Child; Adult; Humans; Male; Fertility Preservation; Semen; Cryopreservation; Oocytes; Infertility; Neoplasms
PubMed: 37807831
DOI: 10.1002/ijgo.15187 -
Journal For Immunotherapy of Cancer Aug 2023CD8tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8 TILs, especially T-cell...
BACKGROUND
CD8tumor infiltrating lymphocytes (TILs) are often observed in non-small cell lung cancers (NSCLC). However, the characteristics of CD8 TILs, especially T-cell populations specific for tumor antigens, remain poorly understood.
METHODS
High throughput single-cell RNA sequencing and single-cell T-cell receptor (TCR) sequencing were performed on CD8 TILs from three surgically-resected lung cancer specimens. Dimensional reduction for clustering was performed using Uniform Manifold Approximation and Projection. CD8 TIL TCR specific for the cancer/testis antigen KK-LC-1 and for predicted neoantigens were investigated. Differentially-expressed gene analysis, Gene Set Enrichment Analysis (GSEA) and single sample GSEA was performed to characterize antigen-specific T cells.
RESULTS
A total of 6998 CD8 T cells was analyzed, divided into 10 clusters according to their gene expression profile. An exhausted T-cell (exhausted T (Tex)) cluster characterized by the expression of (CD39), , (PD1), (TIM3) and other genes, and by T-cell oligoclonality, was identified. The Tex TCR repertoire (Tex-TCRs) contained nine different TCR clonotypes recognizing five tumor antigens including a KK-LC-1 antigen and four neoantigens. By re-clustering the tumor antigen-specific T cells (n=140), it could be seen that the individual T-cell clonotypes were present on cells at different stages of differentiation and functional states even within the same Tex cluster. Stimulating these T cells with predicted cognate peptide indicated that TCR signal strength and subsequent T-cell proliferation and cytokine production was variable but always higher for neoantigens than KK-LC-1.
CONCLUSIONS
Our approach focusing on T cells with an exhausted phenotype among CD8 TILs may facilitate the identification of tumor antigens and clarify the nature of the antigen-specific T cells to specify the promising immunotherapeutic targets in patients with NSCLC.
Topics: Humans; Antigens, Neoplasm; Carcinoma, Non-Small-Cell Lung; CD8-Positive T-Lymphocytes; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Receptors, Antigen, T-Cell; Signal Transduction; Testis
PubMed: 37544663
DOI: 10.1136/jitc-2023-007180