Borgeaud M, Olivier T, Bar J
… +7 more, Saw SPL, Parikh K, Banna GL, De Vito C, Feldman J, Le X, Addeo A
CA Cancer J Clin
· 2025 · PMID 40673977
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The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene has revolutionized the management of lung cancer, enabling the development of targeted tyrosine kinase inhibitors (TKIs). These th...The discovery of activating mutations in the epidermal growth factor receptor (EGFR) gene has revolutionized the management of lung cancer, enabling the development of targeted tyrosine kinase inhibitors (TKIs). These therapies offer improved survival and reduced side effects compared with conventional treatments. Recent advancements have significantly reshaped the treatment paradigm for EGFR-mutant non-small cell lung cancer. TKIs are now incorporated into the management of early stage and locally advanced disease, and phase 3 trials have explored combination strategies in metastatic settings. Although these intensified approaches improve progression-free survival, they come with increased toxicity and higher costs, underscoring the need for precise patient selection to maximize benefit. Emerging data on biomarkers, such as co-mutations and circulating tumor DNA, show promise for refining treatment decisions. In addition, significant progress in understanding resistance mechanisms to EGFR TKIs has broadened therapeutic options. This review provides a comprehensive overview of the current landscape of EGFR-mutant nonsmall cell lung cancer, highlighting recent breakthroughs and discussing strategies to optimize treatment based on the latest evidence.
Chakrabarti D, Albertsen P, Adkins A
… +9 more, Kishan A, Murthy V, Parker C, Pathmanathan A, Reid A, Sartor O, Van As N, Walz J, Tree A
CA Cancer J Clin
· 2025 · PMID 40572035
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Prostate cancer is the most common cancer in two thirds of the world, with an expected doubling in both incidence and mortality in the next two decades. No strong environmental associations exist for the development of p...Prostate cancer is the most common cancer in two thirds of the world, with an expected doubling in both incidence and mortality in the next two decades. No strong environmental associations exist for the development of prostate cancer; therefore, lifestyle measures are unlikely to mitigate this increasing burden. The last three decades have seen rapid developments in the diagnostic and therapeutic landscape of prostate cancer, including multiparametric magnetic resonance imaging, positron emission tomography, robotic surgery, image-guided hypofractionated and stereotactic radiotherapy, novel anti-androgens and radioligand therapies. Prostate cancer is unique in that not everyone with a diagnosis needs treatment, and active surveillance is the preferred option for some. This review discusses the contemporary management of all stages of prostate cancer in the light of these modern developments, enabling holistic individualization of treatment, and describes the promise of future research to further improve outcomes.
Yip W, Jaime-Casas S, Kothari A
… +6 more, Sullivan M, Ballas LK, Escobar D, Schuckman AK, Rosenberg JE, Coleman JA
CA Cancer J Clin
· 2025 · PMID 40478748
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Urothelial carcinoma is an aggressive entity that is associated with significant morbidity, but there have been major advances in both our understanding of and treatment options for patients with this disease. In this re...Urothelial carcinoma is an aggressive entity that is associated with significant morbidity, but there have been major advances in both our understanding of and treatment options for patients with this disease. In this review, the authors focus on novel therapeutic and diagnostic approaches in the perioperative setting, with an emphasis on patient-centered and individualized care. For urothelial carcinoma of the bladder (UCB), advances in nonplatinum-based therapies, specifically immunotherapy and antibody-drug conjugates, have expanded the therapeutic arsenal for patients with muscle-invasive UCB in both the neoadjuvant and adjuvant settings to improve survival outcomes. Given the significant morbidity of extirpative surgery (radical cystectomy and urinary diversion), there have also been greater efforts to evaluate bladder-sparing protocols and improve the selection of patients for surgery and their postoperative recovery. The authors review special considerations for organ-sparing surgery in females, geriatric co-management, and enhanced recovery after surgery protocols. For upper tract urothelial carcinoma, there has been increasing recognition of its unique diagnostic and therapeutic challenges, including risks of renal functional loss. There have been advances in molecular profiling that have demonstrated various genomic differences between upper tract urothelial carcinoma and UCB, with treatment implications. This article reviews studies evaluating perioperative care that focused on optimizing therapeutic approaches, including neoadjuvant/adjuvant chemotherapy and immunotherapy, as well as nephron-sparing strategies in carefully selected cases.
Wagle NS, Nogueira L, Devasia TP
… +7 more, Mariotto AB, Yabroff KR, Islami F, Jemal A, Alteri R, Ganz PA, Siegel RL
CA Cancer J Clin
· 2025 · PMID 40445120
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The number of people living with a history of cancer in the United States continues to rise because of the growth and aging of the population as well as improved survival through advances in early detection and treatment...The number of people living with a history of cancer in the United States continues to rise because of the growth and aging of the population as well as improved survival through advances in early detection and treatment. To assist the public health community serve the needs of these survivors, the American Cancer Society and the National Cancer Institute collaborate triennially to estimate cancer prevalence in the United States using data from the Surveillance, Epidemiology, and End Results cancer registries, the Centers for Disease Control and Prevention's National Center for Health Statistics, and the United States Census Bureau. In addition, cancer treatment patterns are presented from the National Cancer Database along with a brief overview of treatment-related side effects. As of January 1, 2025, about 18.6 million people were living in the United States with a history of cancer, and this number is projected to exceed 22 million by 2035. The three most prevalent cancers are prostate (3,552,460), melanoma of the skin (816,580), and colorectum (729,550) among males and breast (4,305,570), uterine corpus (945,540), and thyroid (859,890) among females. About one half (51%) of survivors were diagnosed within the past 10 years, and nearly four fifths (79%) were aged 60 years and older. Racial differences in treatment in 2021 were common across disease stage; for example, Black people with stage I-II lung cancer were less likely to undergo surgery than their White counterparts (47% vs. 52%). Larger disparities exist for rectal cancer, for which 39% of Black people with stage I disease undergo proctectomy or proctocolectomy compared to 64% of their White counterparts. Targeted, multi-level efforts to expand access to high-quality care and survivorship resources are vital to reducing disparities and advancing support for all survivors of cancer.
Beddok A, Willmann J, Embring A
… +19 more, Appelt AL, Balermpas P, Chua K, Choi JI, Elger BS, Gabrys D, Hoskin P, Niyazi M, Pasquier D, Paradis K, Kaidar-Person O, Plaisier C, Schmitt NC, Steuer CE, Thariat J, Yom SS, Poortmans P, Vasquez Osorio E, Andratschke N
CA Cancer J Clin
· 2025 · PMID 40438993
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Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potenti...Reirradiation (reRT), defined as administering a course of radiation therapy to a specific area previously irradiated, is an evolving treatment strategy for locoregionally recurrent cancer that offers significant potential and poses inherent challenges. Advances in such techniques as intensity-modulated and stereotactic body radiation therapy have improved precision, making reRT a viable option for complex scenarios previously deemed high-risk. Nevertheless, reRT remains associated with substantial risks-including life-threatening side effects, functional impairments, and psychosocial effects-which must be carefully balanced against the patient's overall health and the likelihood of achieving cancer control or palliation. Patient selection is essential to optimize outcomes while mitigating risks. Decisions should account for tumor characteristics at the time of primary diagnosis and recurrence, elapsed time since prior treatment, the possibility of delivering meaningful doses to the tumor, and the cumulative irradiation tolerance of normal tissues. Advanced imaging modalities, such as functional magnetic resonance imaging and fluorine-18-labeled fluorodeoxyglucose-positron emission tomography, are important for distinguishing recurrences from treatment-induced changes, refining treatment targets, and minimizing exposure to healthy tissue. Combined treatment with systemic regimens-targeted therapies and immunotherapy in particular-offers promising opportunities but requires coordination to manage side effects. Standardized guidelines, such as those from the European Society of Therapeutic Radiology and Oncology-European Society for Research and Treatment of Cancer, are essential for improving the consistency of reporting, guiding clinical decision making, and fostering patient-centered care. Multidisciplinary collaboration and ongoing research, particularly through clinical trials, are central to fully exploiting reRT strategies. In addition, the development of innovative techniques, such as proton therapy, would likely enable safer treatments. These efforts aim to improve the therapeutic balance of reRT, enhancing outcomes and quality of life.
CA Cancer J Clin
· 2025 · PMID 40406981
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Approximately one in 3500 to one in 5100 live-born infants have atypical external genital development, known as differences in sex development (DSD). In 2005, an expert consensus conference thoroughly reviewed aspects of...Approximately one in 3500 to one in 5100 live-born infants have atypical external genital development, known as differences in sex development (DSD). In 2005, an expert consensus conference thoroughly reviewed aspects of health care for individuals with DSD. The conference proposed a classification system to help provide individualized evaluations and management. Some types of DSD are associated with germ cell tumors, which comprise a heterogeneous group of neoplasms derived from germline cells. These neoplasms commonly occur in infants, children, adolescents, and young adults. Herein, an overview of DSDs and risks for germ cell tumors is provided.
Moris D, Martinino A, Schiltz S
… +10 more, Allen PJ, Barbas A, Sudan D, King L, Berg C, Kim C, Bashir M, Palta M, Morse MA, Lidsky ME
CA Cancer J Clin
· 2025 · PMID 40392748
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Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-r...Hepatocellular carcinoma (HCC) is the sixth most common malignancy and the third leading cause of cancer-related death worldwide. Contemporary advances in systemic and locoregional therapies have led to changes in peer-reviewed guidelines regarding systemic therapy as well as the possibility of downstaging disease that may enable some patients with advanced disease to ultimately undergo partial hepatectomy or transplantation with curative intent. This review focuses on all modalities of therapy for HCC, guided by modern-day practice-changing randomized data where available. The surgical management of HCC, including resection and transplantation, both of which have evolving criteria for what is considered biologically resectable and transplantable, as well as locoregional therapy (i.e., therapeutic embolization, ablation, radiation, and hepatic arterial infusion), are discussed. Historical and modern-day practice-changing trials evaluating immunotherapy with targeted therapies for advanced disease, as well as adjuvant systemic therapy, are also summarized. In addition, this article examines the critical dimension of toxicities and patient-oriented considerations to ensure a comprehensive and balanced discourse on treatment implications.
Nogueira-Rodrigues A, Oonk MHM, Lorusso D
… +3 more, Slomovitz B, Leitão MM, Baiocchi G
CA Cancer J Clin
· 2025 · PMID 40377134
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Vulvar and vaginal cancers represent rare malignancies, with an incidence of 2.7 per 100,000 women for vulvar cancer, predominantly affecting women older than 60 years, although rising rates are observed in younger demog...Vulvar and vaginal cancers represent rare malignancies, with an incidence of 2.7 per 100,000 women for vulvar cancer, predominantly affecting women older than 60 years, although rising rates are observed in younger demographics. Approximately 90% of vulvar cancers are squamous cell carcinoma and frequently are associated with human papillomavirus (HPV) infection. Vaginal cancer, constituting less than 1% of all female cancers, similarly exhibit HPV-related trends. This review delineates the etiology, histopathology, and treatment strategies for carcinomas and vulvovaginal melanomas and sarcomas. Surgical intervention remains the primary treatment modality for vulvar cancer, involving tumor resection and inguinofemoral lymph node staging. For locally advanced vulvar carcinoma, chemoradiation is advised when exenterative surgery would be indicated. Recurrence rates within 2 years after diagnosis range from 12% to 37%. Unfortunately, systemic treatments for recurrent or metastatic disease are limited, with 5-year survival rates at approximately 20%. Current evidence primarily derives from retrospective studies or small phase 2 trials or otherwise is extrapolated from the treatment of cervical cancer. Enrollment in clinical trials is strongly advocated, along with prompt access to best supportive care to mitigate the effect of locoregional progression on quality of life. Moreover, the psychosocial implications of treatment on body image and sexuality necessitate careful consideration. Future HPV vaccination initiatives may reduce cancer incidence, although significant effects of such vaccination will manifest over decades, underscoring the urgent need to enhance treatment efficacy and minimize morbidity in vulvar and vaginal cancers.
Kordowitzki P, Lange B, Elias KM
… +4 more, Haigis MC, Mechsner S, Braicu IE, Sehouli J
CA Cancer J Clin
· 2025 · PMID 40252048
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High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of all ovarian cancer cases and contributing significantly to the high mortality rate...High-grade serous ovarian cancer (HGSOC) is the most common and aggressive subtype of ovarian cancer, accounting for approximately 70% of all ovarian cancer cases and contributing significantly to the high mortality rates associated with this disease. Because of the asymptomatic nature of early stage disease, most patients are diagnosed at advanced stages when the cancer has already spread into the abdominal cavity, requiring complex and intensive surgical and chemotherapeutic interventions followed by maintenance therapies. Although a minority of cases are associated with well defined genetic syndromes, specific risk factors and a clear etiology in many cases remain elusive. HGSOC tumors are characterized by a high frequency of somatic gene copy number alterations, often associated with defects in homologous recombination repair of DNA. All attempts to introduce an effective screening for HGSOC to date have been unsuccessful. This review elucidates the complexities surrounding HGSOC and encompasses its etiology, epidemiology, classification, pathogenesis, and the current array of treatment strategies. Understanding molecular underpinnings is crucial for the development of targeted therapies and personalized multimodal treatment approaches in centralized therapeutic structures. This review also examines the importance of the tumor microenvironment. In addition, the authors' objective is to underscore the critical importance of placing the patient's perspective and diversity at the forefront of therapeutic strategies, thereby fostering a genuinely participatory decision-making process and ultimately improving patient quality of life.
Sabzevari A, Ung J, Craig JW
… +5 more, Jayappa KD, Pal I, Feith DJ, Loughran TP, O'Connor OA
CA Cancer J Clin
· 2025 · PMID 40232267
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The peripheral T-cell lymphomas (PTCL) are the only disease for which four histone deacetylase (HDAC) inhibitors have been approved globally as single agents. Although it is not clear why the PTCL exhibit such a vulnerab...The peripheral T-cell lymphomas (PTCL) are the only disease for which four histone deacetylase (HDAC) inhibitors have been approved globally as single agents. Although it is not clear why the PTCL exhibit such a vulnerability to these drugs, understanding the biological basis for this activity is essential. Many lines of data have established that the PTCL exhibit marked sensitivity to other epigenetically targeted drugs, including EZH2 and DNMT3 (DNA-methyltransferase 3) inhibitors. Even more compelling is the finding that combinations of drugs targeting the epigenetic biology of PTCL are beginning to produce provocative data, leading some to wonder if these agents can replace historical chemotherapy regimens routinely used for patients with the disease. Simultaneously, the field has identified a spectrum of mutations in genes governing epigenetic biology in many subtypes of PTCL, although the T follicular helper lymphomas, including angioimmunoblastic T-cell lymphoma, appear to be particularly enriched for these genetic features. While the direct relationship between the presence of any one of these mutations and responsiveness to a particular epigenetic drug has yet to be established, it is increasingly accepted that the PTCL may be the prototypical epigenetic disease as no other form of cancer has exhibited such a vulnerability to this diversity of epigenetically targeted agents. Herein, we comprehensively review this esoteric and rapidly evolving field to identify themes and lessons from these experiences that may guide efforts to improve outcomes of patients with T-cell neoplasms. Furthermore, we will discuss how these concepts might be applied to the broader field of cancer medicine.
Juweid ME, Al-Qasem SF, Khuri FR
… +4 more, Gallamini A, Lohmann P, Ziellenbach HJ, Mottaghy FM
CA Cancer J Clin
· 2025 · PMID 40183513
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Cancer molecular imaging is the noninvasive visualization of a process unique to or altered in neoplasia, such as proliferation, glucose metabolism, and receptor expression, which is relevant to patient management. Sever...Cancer molecular imaging is the noninvasive visualization of a process unique to or altered in neoplasia, such as proliferation, glucose metabolism, and receptor expression, which is relevant to patient management. Several molecular imaging modalities are now available, including magnetic resonance, optical, and nuclear imaging. Nuclear imaging, particularly using fluorine-18-fluorodeoxyglucose positron emission tomography, is widely used in the staging and response assessment of multiple cancer types. However, at this writing, new nuclear medicine probes, especially positron emission tomography tracers, are increasingly used or are being investigated for cancer evaluation. This review focuses on these probes, their biologic targets, and the applications or potential applications for their use in the assessment of various neoplasms, including both probes available for commercial use-such as somatostatin receptor ligands in neuroendocrine tumors, prostate-specific membrane antigen ligands in prostate cancer, norepinephrine analogs in neural crest tumors like neuroblastoma, and estrogen analogs in breast cancer-and others in clinical development, such as fibroblast-activating protein inhibitors, C-X-C chemokine receptor type 4 ligands, and monoclonal antibodies targeting receptor tyrosine kinases, CD4-positive or CD8-positive tumor-infiltrating lymphocytes, tumor-associated macrophages, and cancer stem cell biomarkers. These developments represent a major step toward the integration of molecular imaging as a powerful tool in precision medicine, with an expectedly significant impact on patient management and outcome.