CA: A Cancer Journal for Clinicians最新文献

{"title":"Personalizing therapies over the course of hormone receptor-positive/HER2-negative metastatic breast cancer","authors":"Akshara Singareeka Raghavendra MD, MS,&nbsp;Senthil Damodaran MD, PhD,&nbsp;Carlos H. Barcenas MD, MSc,&nbsp;Suzanne A. Fuqua PhD,&nbsp;Rachel M. Layman MD,&nbsp;Debu Tripathy MD","doi":"10.3322/caac.70055","DOIUrl":"10.3322/caac.70055","url":null,"abstract":"<p>The hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer subtype accounts for most early and metastatic breast cancer (MBC) cases. HR-positive/HER2-negative MBC is characterized by a relatively prolonged, although variable, disease course and substantial intertumoral and intratumoral heterogeneity. Although endocrine-based therapies remain the cornerstone of treatment, nearly all patients eventually develop resistance, which is increasingly addressed with biologically targeted agents and newer-generation cytotoxic drugs. This review summarizes the current understanding of HR-positive/HER2-negative MBC biology, highlighting mechanisms of intrinsic and acquired resistance, including driver genomic alterations that, along with clinical factors, help guide therapeutic choices and sequencing. The authors specify and discuss how genomic and transcriptomic profiling inform treatment selection and how side effects and overall patient experience are considered in decision making. Advances in targeted therapies, such as CDK4/6 (cyclin-dependent kinase 4/6), PI3K (phosphatidylinositol 3-kinase), and AKT (protein kinase B) inhibitors, and next-generation estrogen receptor degraders are reviewed along with the expanding role of antibody–drug conjugates and biomarker-guided tumor-agnostic biologic therapies. The authors also explore evolving biologic concepts, including the impact of the tumor microenvironment on resistance and disease progression, and consider the distinct clinical behavior of invasive lobular carcinoma and current approaches. Emerging data from contemporary clinical trials promise to refine clinical and biomarker-driven algorithms and improve outcomes for patients with HR-positive/HER2-negative MBC. Ongoing multi-omic research and adaptive clinical strategies will be essential to further the application of precision oncology in this most common subtype of MBC. Importantly, patient-reported outcomes, shared decision making, and real-world evidence are increasingly useful in formulating comprehensive care plans, guidelines, and policy. The modern treatment landscape features a personalized approach that integrates clinical features, biomarkers, and patient preferences across the disease continuum.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70055","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949885","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pursuit of precision oncology in the treatment of metastatic hormone receptor–positive breast cancer: Making strides or barely moving?","authors":"Ilana Schlam MD, MPH,&nbsp;Ajay Dhakal MBBS","doi":"10.3322/caac.70060","DOIUrl":"10.3322/caac.70060","url":null,"abstract":"&lt;p&gt;Breast cancer is the most common cancer among females in the United States, and metastatic breast cancer is estimated to cause more than 42,000 deaths in 2025.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Hormone receptor (HR)–positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer is the most common subtype of metastatic breast cancer.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Although advances in endocrine and targeted therapies have improved patient outcomes, resistance and disease progression remain common, and the optimal sequencing of available treatments is unknown. In their review, Raghavendra and colleagues present a framework for managing patients with HR-positive, HER2-negative metastatic breast cancer, describing knowledge gaps and the growing role of precision oncology tools, such as genomic profiling of tumor tissue or circulating tumor DNA (ctDNA), in treatment selection.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; The review describes advances in endocrine and targeted therapies that have improved patient outcomes.&lt;/p&gt;&lt;p&gt;As highlighted in the article, there have been two major advances in the treatment of HR-positive metastatic breast cancer over the last decade: first, the approval of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors and, second, the increased use of genomic profiling of tumor tissue and ctDNA for treatment selection, driven primarily by the approval of novel, molecularly targeted therapies that were previously unavailable. An improved understanding of the estrogen receptor pathway and its downstream promotion of the cell cycle has led to the development and approval of CDK4/6 inhibitors in combination with endocrine therapy.&lt;span&gt;&lt;sup&gt;3-6&lt;/sup&gt;&lt;/span&gt; The introduction of these novel drugs is associated with significant improvements in progression-free survival and, in many patients, overall survival as well, making it one of the biggest advancements in the treatment of metastatic HR-positive breast cancer.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; However, some patients do progress early on these therapies, and, as Raghavendra and colleagues have described, it is unclear whether CDK4/6 inhibitors need to be introduced in the first-line setting for all patients.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; To improve precision, we need to develop biomarkers that help identify those patients who have intrinsic resistance to CDK4/6 inhibitors and those who can safely forego the addition of CDK4/6 inhibitors in the first-line setting.&lt;/p&gt;&lt;p&gt;A major shift in recent years has been the routine integration of genomic and molecular characterization using next-generation sequencing (NGS), including analyses of tumor tissue and ctDNA. These tools provide insight into acquired resistance mechanisms, guide targeted therapy selection, and recent data suggest that adaptive treatment changes based on the emergence of genomic alterations, before clinical or radiographic progression, could improve patient outcomes.&lt;span&gt;&lt;sup&gt;8, 9&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;NGS has become the standard for ","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949868","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global incidence of lip, oral cavity, and pharyngeal cancers: Disparities, determinants, and opportunities for prevention, early detection, and treatment","authors":"Fernando Neves Hugo DDS, MSc, PhD","doi":"10.3322/caac.70059","DOIUrl":"10.3322/caac.70059","url":null,"abstract":"&lt;p&gt;Studying cancer incidence by country presents a unique global health opportunity to investigate lip, oral, and pharyngeal cancers (LOPCs), aiming to identify international disparities and understand disease burden across various levels of socioeconomic development. This cross-national approach highlights the central role that social determinants play in shaping LOPC burden inequalities worldwide.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; LOPCs constitute a heterogeneous group of diseases with distinct etiologic profiles and anatomic subsites. Oral cavity cancers are primarily linked to tobacco use in its various forms and alcohol consumption, whereas oropharyngeal cancers share these traditional risk factors but are increasingly associated with high-risk human papillomavirus (HPV) infection, particularly HPV types 16 and 18.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The findings reported by Rumgay and colleagues&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; in this issue of &lt;i&gt;CA: A Cancer Journal for Clinicians&lt;/i&gt; provide a comprehensive overview of LOPC incidence across 185 countries, using estimates from the International Agency for Research on Cancer. The authors estimated 758,000 new cases of LOPC globally in 2022 with a predominance of men (7:1 ratio), with cancers of the oral cavity, followed by the oropharynx and nasopharynx, representing the most incident cases. Their results reveal that oral cavity cancer incidence remains alarmingly high in South-Central Asia, Melanesia, Micronesia, and Polynesia; whereas oropharyngeal cancer rates are elevated in Europe, and represent the most common LOPC subsite among men in North and South America.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Given the distinct etiologies of oral and oropharyngeal cancers, these findings call for equitable health promotion and prevention strategies tailored to specific risk exposures within each country. Rumgay and colleagues&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; appropriately emphasize the World Health Organization (WHO) Framework Convention on Tobacco Control and its MPOWER measures (Monitoring tobacco use; Protecting people from tobacco smoke; Offering help to quit tobacco use; Warning about the dangers of tobacco; Enforcing bans on tobacco advertising, promotion, and sponsorship; and Raising tobacco taxes) as central tools to reduce exposure. Emerging evidence links comprehensive implementation of MPOWER policies with significant reductions in global smoking prevalence and consequent declines in incidence, mortality, and disability-adjusted life-years related to LOPCs.&lt;span&gt;&lt;sup&gt;4, 5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;Efforts to curb alcohol consumption and increase adoption of gender-neutral HPV vaccination are both feasible and essential but have shown uneven progress compared with efforts to reduce consumption of tobacco products. In this regard, the WHO Global Alcohol Action Plan 2022–2030 and the SAFER initiative provide evidence-based, cost-effective strategies. However, evaluations indicate challenges, such as commercial interference, limite","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70059","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145807920","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the cancer divide: Policy and structural solutions for equity in the United States","authors":"Mariana Chavez-MacGregor MD, MSc,&nbsp;Inimfon Jackson MD, MPH, PhD","doi":"10.3322/caac.70054","DOIUrl":"10.3322/caac.70054","url":null,"abstract":"&lt;p&gt;Over the last few decades, there has been significant progress in the fight against cancer. In the United States between 1991 and 2022, cancer-related mortality decreased, with an estimated 4.5 million fewer deaths.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; This is because of numerous factors, including reductions in smoking, early detection for cancers with available screening, and improved therapies in the management of both localized and metastatic cancer.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Despite such improvements, the American Cancer Society's (ACS) Report on the Status of Cancer Disparities by Islami and colleagues that accompanies this editorial, sheds light on the persistent and substantial disparities across the cancer care continuum, including risk factors, incidence, stage at diagnosis, receipt of care, survival, and mortality for many cancers.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; The report evaluates not only the effect of race and ethnicity but also educational status, geographic location, sex, and social determinants of health. In a nation where some of the world’s most advanced treatments and medical technologies are available, it is tragic that not all individuals benefit equally from these innovations. These persistent cancer disparities reflect complex interactions between race and ethnicity, socioeconomic status, and geography.&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; Systemic inequities and policies that have not satisfactorily addressed the most vulnerable have widened the gap between the rich and the poor, disproportionately affecting racial and ethnically minoritized individuals.&lt;span&gt;&lt;sup&gt;5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;According to the 2025 ACS report, the incidence of cancer is higher among Black and American Indian/Alaska Native men and women compared with White individuals across multiple cancers and, notably, these populations also have the highest cancer-related mortality rates.&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; Strategies to improve cancer outcomes have led to a modest narrowing of these gaps over time; however, Black–White mortality disparities persist.&lt;span&gt;&lt;sup&gt;6&lt;/sup&gt;&lt;/span&gt; Although cancer disparities are frequently described according to race and ethnicity, to better understand the implications of this report, it is crucial to detangle the concept of race, which nonetheless remains a strong predictor of higher cancer incidence and worse survival.&lt;span&gt;&lt;sup&gt;7&lt;/sup&gt;&lt;/span&gt; The statistics presented in the ACS report highlight that, beyond race and ethnicity, factors like inequitable access to care, poverty, social determinants of health, and other structural factors are key drivers of disparities and associated poor outcomes, rather than biologic differences alone.&lt;/p&gt;&lt;p&gt;Social determinants of health unequally affect racial and ethnically minoritized individuals, compromising their opportunities to have health care outcomes comparable to those of White populations. Black, American Indian/Alaska Native, and Hispanic individuals are more likely to be poor, less educated, lack health i","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145760078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"American Cancer Society’s Report on the Status of Cancer Disparities in the United States, 2025","authors":"Farhad Islami MD, PhD,&nbsp;Gladys Arias MPA,&nbsp;Dongjun Lee MS,&nbsp;Daniel Wiese PhD,&nbsp;Jordan Baeker Bispo PhD,&nbsp;K. Robin Yabroff PhD,&nbsp;Rebecca L. Siegel MPH,&nbsp;Priti Bandi PhD,&nbsp;Nigar Nargis PhD,&nbsp;Alpa V. Patel PhD,&nbsp;Paul P. Thienprayoon MBA, MS,&nbsp;Arif H. Kamal MD, MBA, MHS,&nbsp;Elvan C. Daniels MD, MPH,&nbsp;Christina M. Annunziata MD, PhD,&nbsp;Kirsten Sloan BA,&nbsp;Lisa A. Lacasse MBA,&nbsp;Robert A. Winn MD,&nbsp;Otis W. Brawley MD, MACP,&nbsp;Carmen E. Guerra MD, MSCE,&nbsp;William L. Dahut MD,&nbsp;Ahmedin Jemal DVM, PhD","doi":"10.3322/caac.70045","DOIUrl":"10.3322/caac.70045","url":null,"abstract":"<p>Since 2021, the American Cancer Society has published its biennial report on the status of cancer disparities in the United States. In this 2025 report, the authors provide updated data on disparities in cancer occurrence and outcomes by sex, race, ethnicity, socioeconomic status (SES [educational attainment as a proxy]), and geographic location (including urbanicity of county of residence and congressional district), along with contributors to these disparities, including major cancer risk factors, screening, and select social determinants of health (SDOH) and health-related social needs. The authors found substantial disparities across the cancer continuum, including risk factors, incidence, stage at diagnosis, receipt of care, survival, and mortality for many cancers and in evaluated SDOH by race and ethnicity, educational attainment, and geographic location. During 2019 through 2023, Black and American Indian/Alaska Native populations had the highest cancer mortality rates, both overall and for the leading causes of cancer death. Cancer mortality rates were also consistently higher among adults with lower SES. However, differences in cancer mortality were substantially larger by education than by race, indicating that SES plays a major role in driving racial disparities in cancer mortality. Overall cancer mortality rates were higher in Black adults than in White adults with the same education level by 7%–28% among males and by 2%–43% among females. Within each race, however, overall cancer mortality rates were higher in adults with ≤12 years of education than in those with ≥16 years of education by 143%–192% among males and by 71%–140% among females. Mortality from all cancers combined was 21% higher in nonmetropolitan than in large metropolitan counties, with the greatest differences for lung (45%) and cervical (36%) cancers and the smallest for prostate, female breast, and pancreatic cancers (7%–8%). By congressional district, the highest cancer mortality rates both overall and for lung, colorectal, and breast cancers were largely found in the South and East North-Central division of the Midwest; however, for prostate cancer, there was no distinct geographic pattern. Sociodemographic groups that had higher cancer mortality generally had higher exposure to risk factors, lower health insurance coverage, and limited access to cancer prevention, early detection, and treatment compared with groups that had lower cancer mortality, largely reflecting fundamental disparities in SDOH. Mitigating cancer disparities in the United States requires intersectoral stakeholder engagement, targeted funding, effective policies at the federal, state, and local levels, and broad implementation of evidence-based interventions, such as expanding health insurance coverage, including through strengthening Marketplaces and protecting and expanding access to Medicaid.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12707308/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761663","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus and controversy in advanced urologic cancers: Insights from the Advanced Urologic Cancer Consensus Conference (AUC3) 2025","authors":"Albert Jang MD,&nbsp;Yousef Zakharia MD,&nbsp;Pedro C. Barata MD, MSc","doi":"10.3322/caac.70056","DOIUrl":"10.3322/caac.70056","url":null,"abstract":"&lt;p&gt;Treatment advances in renal cell carcinoma (RCC) and urothelial carcinoma (UC) have redefined patient outcomes within a single decade, transforming fatal diseases into chronic, manageable conditions for many. The widespread adoption of multitargeted tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and the antibody–drug conjugate enfortumab vedotin (EV) has extended survival compared with historic standards. Yet this progress has introduced new complexity, including overlapping mechanisms, inconsistent success across trials, and limited generalizability because of narrow eligibility criteria along with the lack of reliable predictive biomarkers.&lt;/p&gt;&lt;p&gt;To translate this rapidly expanding evidence base into clinical clarity, the Advanced Urologic Cancer Consensus Conference (AUC3) assembled more than 50 multidisciplinary experts from North America and Europe.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; By using a structured Delphi approach, the panel sought to define consensus thresholds and pinpoint gaps where data remain incomplete and controversial. This editorial highlights the most contentious issues (for which, even among global leaders, consensus was elusive) and frames future directions for investigation.&lt;/p&gt;&lt;p&gt;Pembrolizumab for high-risk clear cell RCC (ccRCC) after nephrectomy remains the first adjuvant regimen to demonstrate an overall survival benefit compared with placebo, as demonstrated in KEYNOTE-564 (ClinicalTrials.gov identifier NCT03142334).&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Strong consensus was reached (&gt;90%) among the panel for high-risk ccRCC including pathologic T3 (pT3) or worse and lymph node-positive disease. Yet situations not addressed in the trial, such as stereotactic body radiation therapy to sites of oligometastatic disease within 1 year of nephrectomy, reached only 65.9% agreement for adjuvant pembrolizumab. Similarly, favorable pathology on the nephrectomy specimen (pT3a tumor, grade 1–2) reached only 54.5% in favor of adjuvant pembrolizumab, with the panel divided over treatment for lower risk patients.&lt;/p&gt;&lt;p&gt;Identifying low-risk patients who may be spared the toxicity of ICI is critical, but predictive biomarkers are lacking. At 72 months, 48.7% of patients receiving placebo in KEYNOTE-564 were still disease-free compared with 58.5% of those receiving pembrolizumab,&lt;span&gt;&lt;sup&gt;3&lt;/sup&gt;&lt;/span&gt; highlighting the importance of predicting the small subset of patients who truly derive benefit from pembrolizumab. Conversely, biomarkers of resistance are needed for the subset of patients likely to have disease relapse despite adjuvant pembrolizumab. They may require upfront adjuvant treatment intensification, and ongoing trials such as STRIKE of adjuvant pembrolizumab with tivozanib (ClinicalTrials.gov identifier NCT06661720) and the recently announced positive trial LITESPARK-022&lt;span&gt;&lt;sup&gt;4&lt;/sup&gt;&lt;/span&gt; of adjuvant pembrolizumab with belzutifan (ClinicalTrials.gov identifier NCT05239728) may offer insight.&lt;/p&gt;&lt;p&gt;Several ","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70056","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced Urologic Cancer Consensus Conference (AUC3) 2025: Expert consensus on the management of renal cell and urinary tract cancers","authors":"Rana R. McKay MD,&nbsp;Sumanta Pal MD,&nbsp;Wanling Xie MS,&nbsp;David Aggen MD, PhD,&nbsp;Laurence Albiges MD, PhD,&nbsp;Andrea Apolo MD,&nbsp;Michael B. Atkins MD,&nbsp;Rick Bangs MBA, PMP,&nbsp;Kathryn E. Beckermann MD, PhD,&nbsp;Joaquim Bellmunt MD, PhD,&nbsp;Stephanie A. Berg DO,&nbsp;Mehmet A. Bilen MD,&nbsp;David Braun MD, PhD,&nbsp;Maria I. Carlo MD,&nbsp;Jason Efstathiou MD, DPhil,&nbsp;Matthew Galsky MD,&nbsp;Petros Grivas MD, PhD,&nbsp;Shilpa Gupta MD,&nbsp;Naomi Haas MD,&nbsp;A. Ari Hakimi MD,&nbsp;Hans Hammers MD, PhD,&nbsp;Daniel Y. C. Heng MSC,&nbsp;Michelle Hirsch MD, PhD,&nbsp;Gopakumar Iyer MD,&nbsp;Eric Jonasch MD,&nbsp;Vadim S. Koshkin MD,&nbsp;Oleksandr Kryvenko MD,&nbsp;Bryan Lewis JD,&nbsp;Roger Li MD,&nbsp;Surena Matin MD,&nbsp;Benjamin Maughan MD, PharmD,&nbsp;David F. McDermott MD,&nbsp;Bradley McGregor MD,&nbsp;Joshua Meeks MD, PhD,&nbsp;Matthew Milowsky MD,&nbsp;Robert Motzer MD,&nbsp;Andrea Necchi MD,&nbsp;Dan Petrylak MD,&nbsp;Sima Porten MD, MPH,&nbsp;Thomas Powles MBBS, MRCP, MD,&nbsp;Brian Rini MD,&nbsp;Brian Shuch MD,&nbsp;Arlene Siefker-Radtke MD,&nbsp;Guru Sonpavde MD,&nbsp;S. Srikala Sridhar MD,&nbsp;Cristina Suarez MD, PhD,&nbsp;Chad Tang MD,&nbsp;Abhishek Tripathi MD,&nbsp;Michiel S. Van Der Heijden MD, PhD,&nbsp;Martin Voss MD,&nbsp;Wenxin Xu MD,&nbsp;Tian Zhang MD,&nbsp;Jonathan Rosenberg MD,&nbsp;Toni K. Choueiri MD","doi":"10.3322/caac.70052","DOIUrl":"10.3322/caac.70052","url":null,"abstract":"<p>The therapeutic landscape for renal cell carcinoma (RCC) and urinary tract cancer (UTC) has transformed dramatically, creating complexity in treatment selection and sequencing. The 2025 Advanced Urologic Cancer Consensus Conference was convened to establish evidence-based expert consensus recommendations for optimal management. A multidisciplinary panel of 51 experts participated in a modified Delphi process addressing questions developed through iterative consensus-building covering RCC and UTC management. Voting occurred before and after the conference, and analyses focused on postmeeting responses. Consensus was defined as ≥75% agreement, with strong consensus as &gt;90%. Strong consensus was found on the use of adjuvant pembrolizumab for higher risk RCC (pathologic T2 [pT2], grade 4; pT3–pT4, any grade; pTXN1; or fully resected metastatic disease) and on neoadjuvant therapy before cystectomy for localized UTC. There was strong consensus on the use of enfortumab vedotin plus pembrolizumab as frontline therapy for metastatic UTC and the use of platinum-based chemotherapy postprogression in biomarker-negative UTC. For RCC, there was consensus on the role of single-agent vascular endothelial growth factor receptor–tyrosine kinase inhibitor therapy after progression on frontline immune checkpoint inhibitor/vascular endothelial growth factor receptor–tyrosine kinase inhibitor therapy or dual immune checkpoint inhibitor therapy. However, there was a lack of consensus on other critical areas in the management of RCC and UTC. The 2025 Advanced Urologic Cancer Consensus Conference provides evidence-informed guidance for complex clinical scenarios while identifying critical research priorities. The group recognizes that the lack of consensus across multiple areas highlights the need for improved patient selection and prospective studies enabling optimal combination and sequencing approaches. This iterative annual process will address evolving treatment paradigms to optimize outcomes.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70052","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145732615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperbaric oxygen therapy for chronic radiotherapy-related adverse effects: A clinically focused review","authors":"Cas Stefaan Dejonckheere MD,&nbsp;Lukas Käsmann MD, MHBA,&nbsp;Leonard Christopher Schmeel MD, MHBA,&nbsp;Stefanie Walter MSc, MBH,&nbsp;Teresa Anzböck MD,&nbsp;Sven Dreyer MD,&nbsp;Gustavo Renato Sarria MD, MHBA,&nbsp;Eleni Gkika MD, MBA,&nbsp;Julian Philipp Layer MD, MHBA","doi":"10.3322/caac.70058","DOIUrl":"10.3322/caac.70058","url":null,"abstract":"<p>Radiotherapy is a cornerstone of modern oncologic care, yet its sequelae can significantly impair survivors' quality of life. Chronic radiation-induced conditions—including skin fibrosis, bone necrosis, radiation cystitis, and proctitis—pose substantial challenges for both patients and caregivers, particularly in the context of improving long-term cancer survival. Hyperbaric oxygen therapy, characterized by the promotion of angiogenesis, fibroblast activation, and tissue remodeling in hypoxic environments, has emerged as a potential adjunctive treatment for mitigating these late effects. Herein, the authors critically evaluate randomized trials, cohort studies, and real-world data while highlighting gaps in knowledge, including patient selection, optimal treatment protocols, and long-term outcomes. In addition, they discuss practical considerations and health system implications of the integration of hyperbaric oxygen therapy into survivorship care. The objective of this review is to provide clinicians with an evidence-informed framework to guide decision making in the multidisciplinary management of radiation-related late effects.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145729117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interventional oncology: A primer for clinicians on the role of ablation and embolization for solid tumors","authors":"Mohamed E. Abdelsalam MD,&nbsp;Kamran Ahrar MD,&nbsp;Rahul A. Sheth MD,&nbsp;Ketan Y. Shah MD,&nbsp;Steven Yevich MD,&nbsp;Varshana Gurusamy MD,&nbsp;Bruno C. Odisio MD,&nbsp;Alda L. Tam MD,&nbsp;Armeen Mahvash MD,&nbsp;Peiman Habibollahi MD","doi":"10.3322/caac.70051","DOIUrl":"10.3322/caac.70051","url":null,"abstract":"<p>Interventional radiology (IR) is a rapidly evolving medical field that combines advanced imaging with minimally invasive techniques for both diagnosis and treatment. Interventional oncology (IO), a subspecialty of IR, focuses on the minimally invasive, image-guided intervention for cancer and cancer-related conditions. IR plays an important and increasingly recognized role within the multidisciplinary care of patients with cancer, contributing meaningfully to diagnosis, therapy, and palliation. IO therapies, particularly tumor ablation and transarterial embolization, aim to target tumors directly while preserving surrounding healthy tissue. These therapies are increasingly supported by clinical guidelines and have shown favorable outcomes in cancers such as hepatocellular carcinoma, renal cell carcinoma, and metastatic colorectal cancer. This review focuses on the role of minimally invasive, image-guided, locoregional IR therapies for patients who have cancer.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145711022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maintenance therapy after first-line therapy for ovarian cancer: Quantitative effectiveness","authors":"Susana M. Campos MD, MPH,&nbsp;Jessica DiSilvestro MD,&nbsp;Stephanie V. Blank MD","doi":"10.3322/caac.70057","DOIUrl":"10.3322/caac.70057","url":null,"abstract":"&lt;p&gt;For patients with ovarian, peritoneal, and fallopian tube carcinoma, completing first-line treatment, maintenance therapy aims to stave off the risk of recurrence with the hope it will improve overall survival. Multiple trials, including the Gynecologic Oncology Group GOG-0218 trial,&lt;span&gt;&lt;sup&gt;1, 2&lt;/sup&gt;&lt;/span&gt; which investigated the vascular endothelial growth factor inhibitor (VEGFi) bevacizumab; SOLO1&lt;span&gt;&lt;sup&gt;3-5&lt;/sup&gt;&lt;/span&gt; (olaparib; ClinicalTrials.gov identifier NCT01844986); PRIMA&lt;span&gt;&lt;sup&gt;6, 7&lt;/sup&gt;&lt;/span&gt; (niraparib; (ClinicalTrials.gov identifier NCT02655016); and PAOLA-1&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; (bevacizumab plus olaparib (ClinicalTrials.gov identifier NCT24777644) have uniquely and independently played pivotal roles in shaping the role of maintenance therapy in this patient population.&lt;/p&gt;&lt;p&gt;Specifically, PAOLA-1&lt;span&gt;&lt;sup&gt;8&lt;/sup&gt;&lt;/span&gt; investigated whether there was value in a combined maintenance strategy. This trial randomly assigned people with ovarian cancer (both homologous recombination-proficient [HRP] and homologous recombination-deficient [HRD]) to receive either maintenance bevacizumab plus the poly (ADP-ribose polymerase) inhibitor (PARPi) olaparib or bevacizumab plus placebo. Compared with bevacizumab plus placebo, there was a significant benefit in progression-free survival (PFS) among patients with HRD disease who received bevacizumab plus olaparib (hazard ratio [HR], 0.41; 95% confidence interval [CI], 0.32–0.54). Among those with HRD disease because of a &lt;i&gt;BRCA1&lt;/i&gt; or &lt;i&gt;BRCA2&lt;/i&gt; mutation, combined treatment resulted in an overall survival benefit (HR, 0.60; 95% CI, 0.39–0.93); this was not reported among those who had HRP disease (HR, 1.19; 95% CI, 0.88–1.63). Despite these results, notable limitations included the omission of a third arm in which participants received a PARPi alone and, as such, questions regarding the true as well as the &lt;i&gt;quantitative effectiveness&lt;/i&gt; of bevacizumab plus olaparib versus treatment with olaparib alone remained unanswered. The only data to suggest a possible benefit to the combination come from an indirect comparison&lt;span&gt;&lt;sup&gt;9&lt;/sup&gt;&lt;/span&gt; of SOLO-1 and PAOLA-1, and the study suggested that adding bevacizumab to olaparib was associated with a &lt;i&gt;numerical&lt;/i&gt;, although not statistically significant, improvement in PFS (HR, 0.71; 95% CI, 0.45–1.09).&lt;/p&gt;&lt;p&gt;In this issue of &lt;i&gt;CA: A Cancer Journal for Clinicians&lt;/i&gt;, we get the results of FZOCUS-1, a randomized trial testing a PARPi, fuzuloparib, with a VEGFi, apatinib, as maintenance treatment after first-line therapy in ovarian cancer.&lt;span&gt;&lt;sup&gt;10&lt;/sup&gt;&lt;/span&gt; Participants were stratified by the presence or absence of germline &lt;i&gt;BRCA1&lt;/i&gt; or &lt;i&gt;BRCA2&lt;/i&gt; mutation and by response to primary treatment. They were randomly assigned 2:2:1 to one of three maintenance arms: fuzuloparib plus apatanib, fuzuloparib plus placebo, or placebo plus placebo.&lt;/p&gt;&lt;p&gt;Compared with placebo, treatment with either fuzuloparib plus placeb","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 1","pages":""},"PeriodicalIF":232.4,"publicationDate":"2025-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}