Anatu H. Saka MPH, Tyler B. Kratzer MPH, Angela N. Giaquinto MSPH, Natalia Mazzitelli MPH, Paulo S. Pinheiro PhD, Ana P. Ortiz PhD, MPH, Dinorah Martinez Tyson PhD, MPH, MA, Ahmedin Jemal DVM, PhD, Rebecca L. Siegel MPH
The Hispanic/Latino population is the second largest racial and ethnic group in the United States, accounting for 20% of the total population (68 million), plus approximately 3 million Hispanic Americans residing in Puerto Rico. Herein, the American Cancer Society reports cancer occurrence, risk factors, and screening for US Hispanic people using federally funded, high-quality, population-based cancer registry data and national vital statistics and survey data. In 2026, an estimated 229,900 Hispanic people will be diagnosed with cancer, and 54,200 will die from the disease in the continental United States and Hawaii. Cancer incidence during 1998–2022 rose in Hispanic women (from 345 to 385 per 100,000) and fell in Hispanic men (from 471 to 389 per 100,000), narrowing the male-to-female incidence rate ratio from a peak of 1.40 (95% CI, 1.38–1.42) in 2002 to 1.01 (95% CI, 1.00–1.02; p = .02) in 2022. This pattern is partly driven by declining incidence of lung and prostate cancers among men and increasing incidence of breast and uterine corpus cancers among women. Although temporal trends mirror the general population, the Hispanic cancer distribution is distinct, consistent with relatively lower prevalence of smoking, alcohol drinking, and screening and higher prevalence of obesity and cancer-causing infections. Compared with White people, Hispanic people have one half the incidence of lung and urinary bladder cancers and 24% lower breast cancer but double the rate of liver, stomach, and gallbladder cancers, 61%–65% higher acute lymphocytic leukemia, and 36% higher cervical cancer. The cancer burden in Puerto Rico is distinct, with lower rates of lung cancer but higher rates of cervical, prostate, and colorectal cancers compared with other US Hispanic populations. Residents in Puerto Rico also experience lasting health care system challenges from extreme weather events. Thus, prevention efforts should target the unique cancer profile of the Hispanic population, including infection prevention and control, healthy eating, physical activity, and routine screening, especially for cervical and colorectal cancer that are 11 percentage points lower than White people.
西班牙/拉丁裔人口是美国第二大种族和族裔群体，占总人口的20%（6800万），加上大约300万居住在波多黎各的西班牙裔美国人。在此，美国癌症协会使用联邦资助的、高质量的、基于人群的癌症登记数据和国家生命统计数据和调查数据，报告了美国西班牙裔人群的癌症发病率、危险因素和筛查。到2026年，估计将有229,900名西班牙裔人被诊断患有癌症，美国大陆和夏威夷将有54200人死于这种疾病。1998-2022年期间，西班牙裔女性的癌症发病率上升（从每10万人345例上升到385例），而西班牙裔男性的癌症发病率下降（从每10万人471例下降到389例），使男女发病率比从2002年的峰值1.40 （95% CI, 1.38-1.42）缩小到2022年的1.01 （95% CI, 1.00-1.02; p = 0.02）。这种模式的部分原因是男性肺癌和前列腺癌发病率下降，而女性乳腺癌和子宫癌发病率上升。虽然时间趋势反映了一般人群，但西班牙裔癌症的分布是明显的，与吸烟、饮酒和筛查的患病率相对较低以及肥胖和致癌感染的患病率较高相一致。与白人相比，西班牙裔人的肺癌和膀胱癌发病率是白人的一半，乳腺癌发病率低24%，但肝癌、胃癌和胆囊癌的发病率是白人的两倍，急性淋巴细胞白血病的发病率高61%-65%，宫颈癌的发病率高36%。波多黎各的癌症负担很明显，与美国其他西班牙裔人口相比，肺癌发病率较低，但宫颈癌、前列腺癌和结直肠癌的发病率较高。波多黎各居民还经历了极端天气事件对医疗保健系统的持续挑战。因此，预防工作应针对西班牙裔人口独特的癌症特征，包括感染预防和控制、健康饮食、体育活动和常规筛查，特别是宫颈癌和结直肠癌，它们的发病率比白人低11个百分点。
{"title":"Cancer statistics for Hispanic/Latino people, 2026","authors":"Anatu H. Saka MPH, Tyler B. Kratzer MPH, Angela N. Giaquinto MSPH, Natalia Mazzitelli MPH, Paulo S. Pinheiro PhD, Ana P. Ortiz PhD, MPH, Dinorah Martinez Tyson PhD, MPH, MA, Ahmedin Jemal DVM, PhD, Rebecca L. Siegel MPH","doi":"10.3322/caac.70107","DOIUrl":"10.3322/caac.70107","url":null,"abstract":"<p>The Hispanic/Latino population is the second largest racial and ethnic group in the United States, accounting for 20% of the total population (68 million), plus approximately 3 million Hispanic Americans residing in Puerto Rico. Herein, the American Cancer Society reports cancer occurrence, risk factors, and screening for US Hispanic people using federally funded, high-quality, population-based cancer registry data and national vital statistics and survey data. In 2026, an estimated 229,900 Hispanic people will be diagnosed with cancer, and 54,200 will die from the disease in the continental United States and Hawaii. Cancer incidence during 1998–2022 rose in Hispanic women (from 345 to 385 per 100,000) and fell in Hispanic men (from 471 to 389 per 100,000), narrowing the male-to-female incidence rate ratio from a peak of 1.40 (95% CI, 1.38–1.42) in 2002 to 1.01 (95% CI, 1.00–1.02; <i>p</i> = .02) in 2022. This pattern is partly driven by declining incidence of lung and prostate cancers among men and increasing incidence of breast and uterine corpus cancers among women. Although temporal trends mirror the general population, the Hispanic cancer distribution is distinct, consistent with relatively lower prevalence of smoking, alcohol drinking, and screening and higher prevalence of obesity and cancer-causing infections. Compared with White people, Hispanic people have one half the incidence of lung and urinary bladder cancers and 24% lower breast cancer but double the rate of liver, stomach, and gallbladder cancers, 61%–65% higher acute lymphocytic leukemia, and 36% higher cervical cancer. The cancer burden in Puerto Rico is distinct, with lower rates of lung cancer but higher rates of cervical, prostate, and colorectal cancers compared with other US Hispanic populations. Residents in Puerto Rico also experience lasting health care system challenges from extreme weather events. Thus, prevention efforts should target the unique cancer profile of the Hispanic population, including infection prevention and control, healthy eating, physical activity, and routine screening, especially for cervical and colorectal cancer that are 11 percentage points lower than White people.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13637640/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101524","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}
<p>Gastric cancer (GC) remains one of the most lethal cancers globally. In this issue of <i>CA: A Cancer Journal for Clinicians</i>, Wang et al. provide a comprehensive review of recent advances across the spectrum of GC.<span><sup>1</sup></span> The rapidly evolving treatment paradigm of metastatic disease is particularly striking and is the focus of this editorial. Clinicians now face questions that were uncommon a decade ago: Which treatment should take priority when several biomarkers are actionable, and how should that choice influence subsequent therapy? The emergence of claudin 18.2 (CLDN18.2)-directed antibodies, antibody–drug conjugates, and cellular therapy makes these questions increasingly relevant.</p><p>For many years, palliative systemic treatment relied almost entirely on cytotoxic chemotherapy along with trastuzumab as an option for human epidermal growth factor receptor 2 (HER2)-positive disease<span><sup>2</sup></span> and the vascular endothelial growth factor 2 (VEGFR2) antagonist ramucirumab as an option after first-line therapy.<span><sup>3</sup></span> Only experimental options were available once these therapies became ineffective or intolerable. This landscape has changed considerably over the past 5 years; Biomarker-driven treatment is now part of routine clinical practice, and actionable targets continue to evolve. The addition of immune checkpoint inhibitors to chemotherapy was one of the recent significant advancements.<span><sup>4-6</sup></span> Programmed death ligand-1 (PD-L1) expression, quantified using the combined positive score (CPS), is used to identify patients most likely to benefit from immunotherapy, with the magnitude of benefit generally increasing with higher CPS. Treatment decisions remain difficult for tumors with low PD-L1 expression, in which the incremental benefit is less clear. Microsatellite instability-high status and, in selected settings, high tumor mutational burden provide additional information regarding the suitability of treatment with immune checkpoint inhibitors, but this pertains to only a relatively small proportion of patients.</p><p>HER2-directed therapy has also expanded. HER2 is overexpressed in a subset of GCs<span><sup>7</sup></span> and has been successfully targeted with trastuzumab, the antibody–drug conjugate fam-trastuzumab deruxtecan-nxki, and the dual HER2-targeted, bispecific antibody zanidatamab. The eligibility criteria for first-line combinations differ. Pembrolizumab with trastuzumab and fluoropyrimidine-containing and platinum-containing chemotherapy is approved by the US Food and Drug Administration (FDA) for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma with a PD-L1 CPS ≥1.<span><sup>5</sup></span> However, the combination of zanidatamab, tislelizumab, and chemotherapy, which was approved by the FDA on August 25, 2026, does not require PD-L1 positivity.<span><sup>6</sup></span> These distinctions matter when
胃癌（GC）仍然是全球最致命的癌症之一。在这一期的《CA: A Cancer Journal for clinical》中，Wang等人对胃癌的最新进展进行了全面回顾。1转移性疾病快速发展的治疗模式尤其引人注目，这也是这篇社论的重点。临床医生现在面临着十年前不常见的问题：当几种生物标志物可用时，应该优先采用哪种治疗方法？这种选择应该如何影响后续治疗？claudin 18.2 （CLDN18.2）定向抗体、抗体-药物偶联物和细胞治疗的出现使得这些问题越来越相关。多年来，姑息性全身治疗几乎完全依赖于细胞毒性化疗和曲妥珠单抗作为人类表皮生长因子受体2 （HER2）阳性疾病2的选择，以及血管内皮生长因子2 （VEGFR2）拮抗剂ramucirumab作为一线治疗后的选择一旦这些疗法变得无效或无法忍受，就只有实验性的选择了。这种情况在过去5年中发生了很大变化；生物标志物驱动的治疗现在是常规临床实践的一部分，可操作的靶点也在不断发展。在化疗中加入免疫检查点抑制剂是最近的重大进展之一。4-6程序性死亡配体-1 （PD-L1）表达，使用联合阳性评分（CPS）进行量化，用于识别最有可能从免疫治疗中获益的患者，获益程度通常随着更高的CPS而增加。对于低PD-L1表达的肿瘤，治疗决策仍然困难，其增量获益不太清楚。微卫星不稳定性-高状态和在特定情况下，高肿瘤突变负担提供了关于免疫检查点抑制剂治疗适用性的额外信息，但这仅适用于相对较小比例的患者。her2定向治疗也在扩大。HER2在GCs7的一个亚群中过表达，并且已经成功地用曲妥珠单抗、抗体-药物偶联物fama -曲妥珠单抗deruxtecan-nxki和双HER2靶向双特异性抗体zanidatamab靶向。一线组合的资格标准有所不同。Pembrolizumab联合曲妥珠单抗和含氟嘧啶和含铂化疗被美国食品和药物管理局（FDA）批准用于一线治疗PD-L1 CPS≥1.5的her2阳性晚期胃或胃食管交界腺癌。然而，2026年8月25日FDA批准的zanidatamab、tislelizumab和化疗联合治疗不需要PD-L1阳性cldn18.2已成为另一个重要靶点，抗cldn18.2单克隆抗体zolbetuximab已被批准用于一线治疗her2阴性、cldn18.2阳性的晚期疾病，并与含氟嘧啶和含铂化疗联合使用这些进展提出了一个越来越重要的临床问题：当不止一种生物标志物可用时，我们该怎么办？这个问题与肿瘤表达CLDN18.2和具有高PD-L1 CPS的患者特别相关。免疫治疗和cldn18.2定向治疗可能是合理的选择。然而，迄今为止，我们只有有限的证据来指导我们应该优先考虑哪些，是否应该将它们结合起来，或者如何对它们进行排序。最近的研究已经开始解决组合问题。在ii期ILUSTRO试验的队列4中，10例her2阴性、cldn18.2阳性疾病患者接受了唑贝妥昔单抗联合纳武单抗和改性亚叶酸蛋白（亚叶酸）、氟尿嘧啶和奥沙利铂（mFOLFOX6）治疗。pd - l1阳性和pd - l1阴性肿瘤均包括在内。疗效和安全性的研究结果支持对该联合的进一步评估，但由于缺乏随机比较，无法得出关于每种药物的作用或其优于现有标准治疗方案的结论。目前正在进行的3期LUCERNA试验旨在评估在her2阴性、cldn18.2阳性、pd - 1阳性疾病患者的化学免疫治疗中加入唑贝妥昔单抗的疗效，将未接受治疗的患者1:1随机分组，分为mFOLFOX或CAPOX（卡培他滨+奥沙利铂）+派姆单抗+唑贝妥昔单抗的试验组，或mFOLFOX或CAPOX +派姆单抗+安慰剂的对照组该试验将阐明在化学免疫治疗中加入唑贝昔单抗的增量益处，尽管它不会确定最佳治疗顺序。CLARITY GASTRIC-02研究（ClinicalTrials）正在评估另一种组合。 该研究评估了抗pd -1和抗tigit双特异性抗体rilvegostomig和抗CLDN18.2的抗体-药物偶联物sonesitatug vedotin与卡佩他滨在CLDN18.2阳性和pd - l1阳性胃食管癌队列1患者中的应用。随着这些方法的发展，治疗选择将需要特定于所考虑的药物和组合的证据。然而，最近最重要的发展可能是细胞疗法的出现。嵌合抗原受体（CAR） t细胞（CAR- t）疗法已经改变了血液系统恶性肿瘤的治疗方法，但在实体肿瘤中取得类似的成功一直很困难。satri-cel是一种cldn18.2靶向疗法，在中国获得批准，标志着CAR-T疗法首次被批准用于实体肿瘤，并表明限制其在实体肿瘤中疗效的一些障碍可能被克服。在先前接受过治疗的her2阴性、cldn18.2阳性、晚期胃癌患者中，与医生选择的治疗相比，sati -cel显示出改善的临床结果这一发展的意义超出了单个药物的功效。它为GC增加了一个新的治疗维度，使CAR-T治疗与现有治疗方法的整合成为一个实际的临床问题。随着其他药物和细胞疗法进入临床实践，关于最佳方案选择和顺序的决定变得更加复杂。除了疗效外，毒性也是方案选择的一个重要特征。针对cldn18.2的抗体疗法可能会导致恶心和呕吐，而CAR-T疗法则会带来一系列不同的副作用，包括细胞因子释放综合征和其他免疫介导的毒性因此，治疗选择将越来越需要考虑治疗靶点、治疗方式、既往治疗、治疗相关毒性、经济负担和患者特征，以及生物标志物，而不是单独考虑生物标志物的存在或不存在。反应的持久性和耐药性仍然是重要的挑战。抗原丢失和下调是公认的细胞治疗耐药机制，实体瘤的抑制性微环境可能会限制细胞治疗的疗效正在研究的方法，包括双靶点car，改善t细胞持久性的策略，以及与检查点抑制剂的联合，可能有助于解决这些限制。它们的临床价值将取决于它们是否在不增加不可接受的毒性的情况下扩大疾病控制。了解每次治疗后的耐药性也可能有助于确定针对同一靶点的另一种药物是否仍然是合理的选择。一个基本的限制是诊断时的单一生物标志物在整个治疗过程中可能不具有代表性。无论是在患者之间还是在单个肿瘤内，GC都是异质的，并且其分子谱可以随着治疗而变化。在诊断时获得的单一活检可能在其病程后期提供疾病的不完整图像。结合序列分子谱、循环肿瘤DNA和其他多组学方法，可以使治疗决策反映肿瘤如何随时间变化，而不是依赖于静态的生物标志物结果。Wang等人描述了一个发生了实质性变化的领域。问题不再仅仅是转移性胃癌患者是否有可操作的生物标志物。越来越多的挑战将是确定在疾病病程的特定时间点哪种生物标志物最重要，以及如何组合或排序可用的治疗方法。对于cldn18.2定向治疗，这包括使用抗体或抗体-药物偶联物治疗是否会影响细胞治疗的后续获益。试验应关注治疗结果、顺序和生活质量。CAR-T疗法最终是否会成为全球胃癌常规治疗的一部分仍有待确定，但CAR-T疗法首次被批准用于实体肿瘤，这使得其在治疗序列中的位置规划尤为及时。利益冲突声明lindsey M. Hannan在提交的工作之外报告了来自阿斯利康、Coherus生物科学公司和强生公司的资助/合同。Vaia Florou曾担任顾问或顾问：Aadi Bioscience， Deciphera, SpringWorks Therapeutics, Merus, Ipsen, Exelixis
{"title":"A changing landscape in gastric cancer","authors":"Lindsay M. Hannan MD, MSPH, Vaia Florou MD, MS","doi":"10.3322/caac.70113","DOIUrl":"10.3322/caac.70113","url":null,"abstract":"<p>Gastric cancer (GC) remains one of the most lethal cancers globally. In this issue of <i>CA: A Cancer Journal for Clinicians</i>, Wang et al. provide a comprehensive review of recent advances across the spectrum of GC.<span><sup>1</sup></span> The rapidly evolving treatment paradigm of metastatic disease is particularly striking and is the focus of this editorial. Clinicians now face questions that were uncommon a decade ago: Which treatment should take priority when several biomarkers are actionable, and how should that choice influence subsequent therapy? The emergence of claudin 18.2 (CLDN18.2)-directed antibodies, antibody–drug conjugates, and cellular therapy makes these questions increasingly relevant.</p><p>For many years, palliative systemic treatment relied almost entirely on cytotoxic chemotherapy along with trastuzumab as an option for human epidermal growth factor receptor 2 (HER2)-positive disease<span><sup>2</sup></span> and the vascular endothelial growth factor 2 (VEGFR2) antagonist ramucirumab as an option after first-line therapy.<span><sup>3</sup></span> Only experimental options were available once these therapies became ineffective or intolerable. This landscape has changed considerably over the past 5 years; Biomarker-driven treatment is now part of routine clinical practice, and actionable targets continue to evolve. The addition of immune checkpoint inhibitors to chemotherapy was one of the recent significant advancements.<span><sup>4-6</sup></span> Programmed death ligand-1 (PD-L1) expression, quantified using the combined positive score (CPS), is used to identify patients most likely to benefit from immunotherapy, with the magnitude of benefit generally increasing with higher CPS. Treatment decisions remain difficult for tumors with low PD-L1 expression, in which the incremental benefit is less clear. Microsatellite instability-high status and, in selected settings, high tumor mutational burden provide additional information regarding the suitability of treatment with immune checkpoint inhibitors, but this pertains to only a relatively small proportion of patients.</p><p>HER2-directed therapy has also expanded. HER2 is overexpressed in a subset of GCs<span><sup>7</sup></span> and has been successfully targeted with trastuzumab, the antibody–drug conjugate fam-trastuzumab deruxtecan-nxki, and the dual HER2-targeted, bispecific antibody zanidatamab. The eligibility criteria for first-line combinations differ. Pembrolizumab with trastuzumab and fluoropyrimidine-containing and platinum-containing chemotherapy is approved by the US Food and Drug Administration (FDA) for first-line treatment of HER2-positive advanced gastric or gastroesophageal junction adenocarcinoma with a PD-L1 CPS ≥1.<span><sup>5</sup></span> However, the combination of zanidatamab, tislelizumab, and chemotherapy, which was approved by the FDA on August 25, 2026, does not require PD-L1 positivity.<span><sup>6</sup></span> These distinctions matter when ","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101591","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}
Amar U. Kishan MD, Yulia Zekster MD, Adam E. Singer MD, PhD, Kekoa Taparra MD, PhD, MPH, Luca F. Valle MD, Michael L. Steinberg MD, Nicholas G. Nickols MD, PhD, Robert E. Reiter MD, MBA, Johannes Czernin MD, Jeremie Calais MD, PhD, John K. Lee MD, PhD, Lawrence R. Hardesty BS, Matthew B. Rettig MD
<p>A man aged 76 years in good health presented for evaluation of a rising prostate-specific antigen (PSA) level after prior radical prostatectomy (Figure 1). Briefly, his prostate cancer had been diagnosed 5 years prior in the setting of a rising PSA. A standard biopsy had revealed International Society of Urological Pathology (ISUP) grade group 3 disease, and he underwent radical prostatectomy without pelvic nodal sampling. Pathologic examination demonstrated extracapsular extension and the presence of intraductal carcinoma; otherwise, at final pathology, the tumor was ISUP grade group 3, with negative surgical margins but evidence of perineural invasion. Postoperative PSA was undetectable for 3 years and then began to slowly rise, reaching 0.06 ng/dL 42 months after surgery. PSA then began to rise more rapidly, reaching 0.37 ng/dL 51 months after surgery. He underwent a prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scan at that time, which showed an enhancing nodular soft tissue along the right prostate bed (1.1 × 0.5 cm) with intense PSMA uptake, as well as uptake in a 3-mm right internal iliac node, a 3-mm right common iliac node, and a 3-mm aortocaval node (Figure 2). Focal uptake in a left presacral area was thought to represent a ganglion, whereas uptake in the T11 vertebral body was equivocal; follow-up magnetic resonance imaging (MRI) of the thoracic spine confirmed that the T11 lesion was a hemangioma. MRI of the prostate bed showed a small focus of T2-hypointense soft tissue in the right pelvis lateral to the prostatectomy bed measuring 15 × 5 mm.</p><p>The patient was evaluated by a radiation oncologist, urologist, and medical oncologist, and decided to pursue a clinical trial of stereotactic body radiotherapy (SBRT; ClinicalTrials.gov identifier NCT03541850).<span><sup>1</sup></span> He received 40 grays (Gy) in five fractions to the prostate bed gross nodule and PSMA-positive nodes, 30 Gy in five fractions to the prostate bed, and 25 Gy in five fractions to the elective lymph node regions. In addition to SBRT, he started a planned short course of androgen-deprivation therapy (ADT; this was allowed on the protocol) but stopped after 1 month because of intolerance. PSA dropped to 0.18 ng/dL 6 months after SBRT, but then rose to 0.27 ng/dL 3months later and 0.99 ng/dL 6 months after that (now nearly 6 years after his prostatectomy). PSMA PET/CT imaging revealed a decrease in size and positivity of the right internal iliac node, with stable low uptake in the right CI node and prostate bed, and resolution of the aortocaval node. However, there was new uptake in two 4–6 mm left para-aortic nodes and a 5-mm node anterior to the aorta (Figure 3).</p><p>The patient enrolled on a trial of PSMA PET/CT–guided, metastasis-directed therapy (MDT) with 6 months of androgen-annihilation therapy (AAT; leuprolide, apalutamide, and abiraterone; ClinicalTrials.gov identifier NCT03902951).<span><sup>
{"title":"Recurrent prostate adenocarcinoma after radical prostatectomy: Principles of multidisciplinary management across a spectrum of disease","authors":"Amar U. Kishan MD, Yulia Zekster MD, Adam E. Singer MD, PhD, Kekoa Taparra MD, PhD, MPH, Luca F. Valle MD, Michael L. Steinberg MD, Nicholas G. Nickols MD, PhD, Robert E. Reiter MD, MBA, Johannes Czernin MD, Jeremie Calais MD, PhD, John K. Lee MD, PhD, Lawrence R. Hardesty BS, Matthew B. Rettig MD","doi":"10.3322/caac.70111","DOIUrl":"10.3322/caac.70111","url":null,"abstract":"<p>A man aged 76 years in good health presented for evaluation of a rising prostate-specific antigen (PSA) level after prior radical prostatectomy (Figure 1). Briefly, his prostate cancer had been diagnosed 5 years prior in the setting of a rising PSA. A standard biopsy had revealed International Society of Urological Pathology (ISUP) grade group 3 disease, and he underwent radical prostatectomy without pelvic nodal sampling. Pathologic examination demonstrated extracapsular extension and the presence of intraductal carcinoma; otherwise, at final pathology, the tumor was ISUP grade group 3, with negative surgical margins but evidence of perineural invasion. Postoperative PSA was undetectable for 3 years and then began to slowly rise, reaching 0.06 ng/dL 42 months after surgery. PSA then began to rise more rapidly, reaching 0.37 ng/dL 51 months after surgery. He underwent a prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scan at that time, which showed an enhancing nodular soft tissue along the right prostate bed (1.1 × 0.5 cm) with intense PSMA uptake, as well as uptake in a 3-mm right internal iliac node, a 3-mm right common iliac node, and a 3-mm aortocaval node (Figure 2). Focal uptake in a left presacral area was thought to represent a ganglion, whereas uptake in the T11 vertebral body was equivocal; follow-up magnetic resonance imaging (MRI) of the thoracic spine confirmed that the T11 lesion was a hemangioma. MRI of the prostate bed showed a small focus of T2-hypointense soft tissue in the right pelvis lateral to the prostatectomy bed measuring 15 × 5 mm.</p><p>The patient was evaluated by a radiation oncologist, urologist, and medical oncologist, and decided to pursue a clinical trial of stereotactic body radiotherapy (SBRT; ClinicalTrials.gov identifier NCT03541850).<span><sup>1</sup></span> He received 40 grays (Gy) in five fractions to the prostate bed gross nodule and PSMA-positive nodes, 30 Gy in five fractions to the prostate bed, and 25 Gy in five fractions to the elective lymph node regions. In addition to SBRT, he started a planned short course of androgen-deprivation therapy (ADT; this was allowed on the protocol) but stopped after 1 month because of intolerance. PSA dropped to 0.18 ng/dL 6 months after SBRT, but then rose to 0.27 ng/dL 3months later and 0.99 ng/dL 6 months after that (now nearly 6 years after his prostatectomy). PSMA PET/CT imaging revealed a decrease in size and positivity of the right internal iliac node, with stable low uptake in the right CI node and prostate bed, and resolution of the aortocaval node. However, there was new uptake in two 4–6 mm left para-aortic nodes and a 5-mm node anterior to the aorta (Figure 3).</p><p>The patient enrolled on a trial of PSMA PET/CT–guided, metastasis-directed therapy (MDT) with 6 months of androgen-annihilation therapy (AAT; leuprolide, apalutamide, and abiraterone; ClinicalTrials.gov identifier NCT03902951).<span><sup>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13620192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072953","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}
Feng Wang MD, PhD, 王峰, Zi-Xian Wang MD, PhD, 王梓贤, Yu-Jing Zhang MD, PhD, 张玉晶, Ye He MD, PhD, 何叶, Jia-Fu Ji MD, PhD, 季加孚, Yuan-Fang Li MD, PhD, 李元方, Xiu-Juan Qu MD, PhD, 曲秀娟, Yi Ba MD, PhD, 巴一, Shu-Qiang Yuan MD, PhD, 袁庶强, Rui-Hua Xu MD, PhD, 徐瑞华
Gastric cancer remains a leading cause of cancer-related mortality worldwide, with nearly 1 million new cases diagnosed annually. Despite innovations in diagnosis, most patients still present at advanced stages, contributing to a poor prognosis. For early gastric cancer, endoscopic resection or minimally invasive surgery has become standard, offering comparable oncologic outcomes with faster recovery compared with open surgery. In locally advanced disease, resection of the primary lesion and D2 lymphadenectomy, defined as dissection of lymph nodes along two levels of blood vessels supplying the stomach, remains the cornerstone of curative surgery, whereas perioperative chemotherapy, particularly oxaliplatin-based regimens, has demonstrated improved survival benefits compared with surgery alone. The integration of immunotherapy into perioperative therapy for locally advanced disease and first-line palliative therapy for metastatic disease represents a paradigm shift, with programmed death 1/programmed death-ligand 1 inhibitors combined with chemotherapy significantly improving pathologic complete response rates and overall survival, especially in programmed death ligand 1–positive and microsatellite instability-high tumors. Targeted agents include claudin 18.2 antibody, with zolbetuximab establishing a new first-line standard for claudin 18.2–positive disease, and antibody–drug conjugates, such as trastuzumab deruxtecan for human epidermal growth factor receptor 2–positive disease, both of which have revolutionized treatment paradigms. Emerging strategies include dual immune checkpoint inhibition, bispecific antibodies, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor 2b–targeting agents. Ultimately, the field is moving toward personalized, biomarker-driven approaches within multidisciplinary frameworks, although overcoming acquired resistance and addressing global disparities in therapeutic access remain important challenges.
{"title":"Advances in therapeutic approaches to gastric cancer","authors":"Feng Wang MD, PhD, 王峰, Zi-Xian Wang MD, PhD, 王梓贤, Yu-Jing Zhang MD, PhD, 张玉晶, Ye He MD, PhD, 何叶, Jia-Fu Ji MD, PhD, 季加孚, Yuan-Fang Li MD, PhD, 李元方, Xiu-Juan Qu MD, PhD, 曲秀娟, Yi Ba MD, PhD, 巴一, Shu-Qiang Yuan MD, PhD, 袁庶强, Rui-Hua Xu MD, PhD, 徐瑞华","doi":"10.3322/caac.70103","DOIUrl":"10.3322/caac.70103","url":null,"abstract":"<p>Gastric cancer remains a leading cause of cancer-related mortality worldwide, with nearly 1 million new cases diagnosed annually. Despite innovations in diagnosis, most patients still present at advanced stages, contributing to a poor prognosis. For early gastric cancer, endoscopic resection or minimally invasive surgery has become standard, offering comparable oncologic outcomes with faster recovery compared with open surgery. In locally advanced disease, resection of the primary lesion and D2 lymphadenectomy, defined as dissection of lymph nodes along two levels of blood vessels supplying the stomach, remains the cornerstone of curative surgery, whereas perioperative chemotherapy, particularly oxaliplatin-based regimens, has demonstrated improved survival benefits compared with surgery alone. The integration of immunotherapy into perioperative therapy for locally advanced disease and first-line palliative therapy for metastatic disease represents a paradigm shift, with programmed death 1/programmed death-ligand 1 inhibitors combined with chemotherapy significantly improving pathologic complete response rates and overall survival, especially in programmed death ligand 1–positive and microsatellite instability-high tumors. Targeted agents include claudin 18.2 antibody, with zolbetuximab establishing a new first-line standard for claudin 18.2–positive disease, and antibody–drug conjugates, such as trastuzumab deruxtecan for human epidermal growth factor receptor 2–positive disease, both of which have revolutionized treatment paradigms. Emerging strategies include dual immune checkpoint inhibition, bispecific antibodies, chimeric antigen receptor T-cell therapy, and fibroblast growth factor receptor 2b–targeting agents. Ultimately, the field is moving toward personalized, biomarker-driven approaches within multidisciplinary frameworks, although overcoming acquired resistance and addressing global disparities in therapeutic access remain important challenges.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987443","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}
Clarissa Mathias MD, PhD, Fabio Ynoe Moraes MD, PhD, MBA
<p>For decades, the management of early stage nonsmall cell lung cancer (NSCLC) was guided primarily by anatomic staging and surgical resection. Although this approach has achieved favorable outcomes for many patients, it does not fully account for the biologic heterogeneity that influences recurrence risk and treatment response. Contemporary advances in lung cancer screening, surgical techniques, precision radiotherapy, molecular profiling, and perioperative systemic therapies have collectively transformed the therapeutic landscape, supporting a more risk-adaptive approach that integrates anatomic, biologic, and patient-specific factors into clinical decision-making.</p><p>In this context, the review by Zhang et al.<span><sup>1</sup></span> provides a comprehensive overview of the advances that are reshaping the management of localized NSCLC. Progress in lung cancer screening, minimally invasive and parenchyma-sparing surgery, stereotactic ablative radiotherapy (SABR) and other highly conformal radiotherapy techniques, together with the integration of perioperative immunotherapy and molecularly targeted therapies, has broadened the therapeutic landscape and enabled increasingly individualized treatment approaches.</p><p>Importantly, the review highlights the evolving limitations of relying solely on the tumor-node-metastasis classification to guide treatment decisions. Although tumor-node-metastasis staging remains the cornerstone of prognostic assessment and therapeutic planning, it provides limited information regarding tumor biology, host immune interactions, or the likelihood of micrometastatic disease.<span><sup>2</sup></span> The increasing availability of molecular profiling, circulating tumor DNA analysis, and other emerging biomarkers offers opportunities to complement anatomic staging with biologic risk assessment, potentially enabling more individualized treatment strategies. Rather than replacing established staging systems, these advances support a more integrated framework in which anatomic extent of disease, molecular alterations, immune characteristics, and dynamic biomarkers collectively inform clinical decision-making. As the field continues to evolve, the central challenge will be determining how these emerging tools can be incorporated into evidence-based care while maintaining equitable access across diverse health care settings.</p><p>The widespread implementation of low-dose computed tomography screening has fundamentally altered the presentation of NSCLC. Landmark trials, specifically the National Lung Screening Trial<span><sup>3</sup></span> and the NELSON trial,<span><sup>4</sup></span> have demonstrated significant mortality reductions, cementing low-dose computed tomography as the gold standard for high-risk populations. However, this screening success has precipitated a <i>stage migration</i>, characterized by a dramatic increase in the detection of early stage lesions, particularly ground-glass opacities.</p><p>Simu
{"title":"Redefining early stage nonsmall cell lung cancer: The dawn of the risk-adaptive and biologically precise era","authors":"Clarissa Mathias MD, PhD, Fabio Ynoe Moraes MD, PhD, MBA","doi":"10.3322/caac.70102","DOIUrl":"10.3322/caac.70102","url":null,"abstract":"<p>For decades, the management of early stage nonsmall cell lung cancer (NSCLC) was guided primarily by anatomic staging and surgical resection. Although this approach has achieved favorable outcomes for many patients, it does not fully account for the biologic heterogeneity that influences recurrence risk and treatment response. Contemporary advances in lung cancer screening, surgical techniques, precision radiotherapy, molecular profiling, and perioperative systemic therapies have collectively transformed the therapeutic landscape, supporting a more risk-adaptive approach that integrates anatomic, biologic, and patient-specific factors into clinical decision-making.</p><p>In this context, the review by Zhang et al.<span><sup>1</sup></span> provides a comprehensive overview of the advances that are reshaping the management of localized NSCLC. Progress in lung cancer screening, minimally invasive and parenchyma-sparing surgery, stereotactic ablative radiotherapy (SABR) and other highly conformal radiotherapy techniques, together with the integration of perioperative immunotherapy and molecularly targeted therapies, has broadened the therapeutic landscape and enabled increasingly individualized treatment approaches.</p><p>Importantly, the review highlights the evolving limitations of relying solely on the tumor-node-metastasis classification to guide treatment decisions. Although tumor-node-metastasis staging remains the cornerstone of prognostic assessment and therapeutic planning, it provides limited information regarding tumor biology, host immune interactions, or the likelihood of micrometastatic disease.<span><sup>2</sup></span> The increasing availability of molecular profiling, circulating tumor DNA analysis, and other emerging biomarkers offers opportunities to complement anatomic staging with biologic risk assessment, potentially enabling more individualized treatment strategies. Rather than replacing established staging systems, these advances support a more integrated framework in which anatomic extent of disease, molecular alterations, immune characteristics, and dynamic biomarkers collectively inform clinical decision-making. As the field continues to evolve, the central challenge will be determining how these emerging tools can be incorporated into evidence-based care while maintaining equitable access across diverse health care settings.</p><p>The widespread implementation of low-dose computed tomography screening has fundamentally altered the presentation of NSCLC. Landmark trials, specifically the National Lung Screening Trial<span><sup>3</sup></span> and the NELSON trial,<span><sup>4</sup></span> have demonstrated significant mortality reductions, cementing low-dose computed tomography as the gold standard for high-risk populations. However, this screening success has precipitated a <i>stage migration</i>, characterized by a dramatic increase in the detection of early stage lesions, particularly ground-glass opacities.</p><p>Simu","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910286","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}
Chaoqi Zhang MD, PhD, 张超奇, Xuanyu Gu MD, 谷炫谕, Pan Wang MD, 王攀, Dongyu Li MD, 李东宇, Guochao Zhang MD, 张国超, Ting Wang MD, PhD, 王婷, Peng Wu PhD, 吴芃, Wei Rao MD, 饶薇, Shan Muhammad PhD, Binghua Tan MD, 谭炳华, Yun Che MD, PhD, 车云, Mobai Zhu MD, 朱墨白, Qilin Qiao MD, 乔奇临, Fanbo Lai MD, 来凡博, Bohui Zhao MD, 赵博慧, Kailun Fei MD, 费凯伦, Yue Wu PhD, 吴玥, Zhihui Zhang PhD, 张志慧, Min Dai PhD, 代敏, Wanqing Chen MD, PhD, 陈万青, Yawei Zhang PhD, 张亚玮, Nan Bi MD, 毕楠, Jie Wang MD, 王洁, Jie He MD, PhD, 赫捷
The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence–driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.
{"title":"Early stage nonsmall cell lung cancer: Toward a risk-adaptive paradigm in the era of biologic precision","authors":"Chaoqi Zhang MD, PhD, 张超奇, Xuanyu Gu MD, 谷炫谕, Pan Wang MD, 王攀, Dongyu Li MD, 李东宇, Guochao Zhang MD, 张国超, Ting Wang MD, PhD, 王婷, Peng Wu PhD, 吴芃, Wei Rao MD, 饶薇, Shan Muhammad PhD, Binghua Tan MD, 谭炳华, Yun Che MD, PhD, 车云, Mobai Zhu MD, 朱墨白, Qilin Qiao MD, 乔奇临, Fanbo Lai MD, 来凡博, Bohui Zhao MD, 赵博慧, Kailun Fei MD, 费凯伦, Yue Wu PhD, 吴玥, Zhihui Zhang PhD, 张志慧, Min Dai PhD, 代敏, Wanqing Chen MD, PhD, 陈万青, Yawei Zhang PhD, 张亚玮, Nan Bi MD, 毕楠, Jie Wang MD, 王洁, Jie He MD, PhD, 赫捷","doi":"10.3322/caac.70100","DOIUrl":"10.3322/caac.70100","url":null,"abstract":"<p>The clinical landscape of early stage nonsmall cell lung cancer is at transformative crossroads. Driven by the widespread adoption of low-dose computed tomography screening, the frequent detection of ground-glass opacities, and a rising incidence among never-smokers, the diagnostic center of gravity has shifted toward earlier, potentially curable disease. This shift has been accompanied by equally important therapeutic advances, including parenchyma-sparing surgical techniques, minimally invasive platforms enhanced by digital navigation, and the transformative integration of perioperative immunotherapy and targeted agents. Concurrently, noninvasive monitoring approaches, such as liquid biopsy, have emerged as powerful tools to guide precision management. Despite this progress, substantial barriers to achieving a universal cure persist. Clinicians continue to face uncertainty in the management of ground-glass opacities, the anatomy-based TNM staging system fails to capture the biologic heterogeneity of early tumors, and global disparities in access to innovation remain unresolved. To address these challenges, the authors propose a shift toward a risk-adaptive management paradigm that harnesses artificial intelligence–driven analytics and multi-omics profiling to tailor treatment intensity according to each patient's biologic risk. Such an approach would enable appropriate escalation for high-risk individuals while permitting safe de-escalation for those at low risk. This holistic, lifespan-oriented strategy must be embraced to deliver equitable and durable cures for patients with early stage nonsmall cell lung cancer.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70100","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148910240","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}
Alexander B. Olawaiye MD, Elliot A. Asare MD, MS, Ian S. Hagemann MD, PhD, Priya R. Bhosale MD, MBA, Stephanie Gaillard MD, PhD, Brian Rous MBBChir, PhD, Bunja Rungruang MD, Shitanshu Uppal MD, MBA, Gulisa Turashvili MD, PhD, Kaled M. Alektiar MD, Jonathan A. Cosin MD, Uma Krishnamurti MD, PhD, Lee-may Chen MD, Keiichi Fujiwara MD, PhD, Matthew A. Powell MD, Mauricio A. Cuello MD, PhD, David G. Mutch MD
The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for all cancer sites has been updated periodically as a published manual for many years. The last update of the manual version, the eighth edition AJCC Cancer Staging Manual, went into use on January 1, 2018. The AJCC has since restructured and updated its processes for curating, analyzing, and publishing updates to the TNM staging system. All AJCC staging-related data are now housed on its new application programming interface. Consequently, the subsequent AJCC TNM staging updates are now published electronically as protocols and are released by disease sites. The protocol for carcinoma of the vulva, AJCC version 9, is now published. The new TNM vulvar cancer staging was validated using the American College of Surgeons’ National Cancer Data Base. This article highlights the changes to the new AJCC TNM staging protocol for carcinoma of the vulva; these changes align with the 2021 International Federation for Gynecology and Obstetrics staging. The most important of the changes are: (1) a new method for depth of invasion measurement, (2) the addition of a new T subcategory—T4, (3) redefined N subcategories, and (4) an increased number of M subcategories with the addition of clinical to all M subcategories.
{"title":"The new (version 9) American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging protocol for carcinoma of the vulva","authors":"Alexander B. Olawaiye MD, Elliot A. Asare MD, MS, Ian S. Hagemann MD, PhD, Priya R. Bhosale MD, MBA, Stephanie Gaillard MD, PhD, Brian Rous MBBChir, PhD, Bunja Rungruang MD, Shitanshu Uppal MD, MBA, Gulisa Turashvili MD, PhD, Kaled M. Alektiar MD, Jonathan A. Cosin MD, Uma Krishnamurti MD, PhD, Lee-may Chen MD, Keiichi Fujiwara MD, PhD, Matthew A. Powell MD, Mauricio A. Cuello MD, PhD, David G. Mutch MD","doi":"10.3322/caac.70104","DOIUrl":"https://doi.org/10.3322/caac.70104","url":null,"abstract":"<p>The American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for all cancer sites has been updated periodically as a published manual for many years. The last update of the manual version, the eighth edition <i>AJCC Cancer Staging Manual</i>, went into use on January 1, 2018. The AJCC has since restructured and updated its processes for curating, analyzing, and publishing updates to the TNM staging system. All AJCC staging-related data are now housed on its new application programming interface. Consequently, the subsequent AJCC TNM staging updates are now published electronically as protocols and are released by disease sites. The protocol for carcinoma of the vulva, AJCC version 9, is now published. The new TNM vulvar cancer staging was validated using the American College of Surgeons’ National Cancer Data Base. This article highlights the changes to the new AJCC TNM staging protocol for carcinoma of the vulva; these changes align with the 2021 International Federation for Gynecology and Obstetrics staging. The most important of the changes are: (1) a new method for depth of invasion measurement, (2) the addition of a new T subcategory—T4, (3) redefined N subcategories, and (4) an increased number of M subcategories with the addition of <i>clinical</i> to all M subcategories.</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70104","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849263","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}
In order to maintain the high standards of CA’s content, the Editors of CA rely on the knowledge and dedication of many experts in deciding which topics to pursue, which manuscripts to publish, and what modifications to make to ensure medical and scientific accuracy and suitability for our readers. We thank our Associate Editors and our Editorial Advisory Board, who continue to provide these services for us time and time again.
We are also greatly indebted to the effort and expertise of the following individuals for reviewing manuscripts for the journal from July 1, 2025, to June 30, 2026. These individuals go beyond expectations by consistently and expeditiously delivering comprehensive, discerning reviews.
Nadeem R. Abu-Rustum
Pedro Barata
Surinder Batra
Beth Beadle
Daniel Benedetti
Sushil Beriwal
Stephanie Blank
Susana Campos
Fumiko Chino
Clay Cockerell
Adil Daud
Michael Davies
Ajay Dhakal
Jessica DiSilvestro
Milana Dolezal
Julien Edeline
Bita Esmaeli
Douglas Evans
Vaia Florou
Zhi Ven Fong
Anand Ganesan
Ben George
Amandeep Godara
Krishna Gunturu
Lindsay Hannan
Jeremy Harris
Kate Hetherington
Kathleen Horst
Fernando Hugo
Ahmedin Jemal
Rachel Jimenez
Corinne Joshu
Hina Khan
Albert E. Kim
Kevin B. Kim
Matthew Kudek
Matteo Lambertini
Phebe Lemert
Gilberto Lopes de Lima Lopes Junior
Stefano Luminari
Martin Ma
Kim Margolin
Carol Marquez
Jonathan Marron
Claudia Massarotti
Paul Mathew
Clarissa Mathias
Sandy Mazzoni
Krishnan Patel
Mack Roach
Ilana Schlam
Vivek Subbiah
Molly Taylor
Derek Tsang
Angela E. Usher
Hao Wang
Lori Wirth
Fabio Ynoe de Moraes
Youssef Zeidan
Mu-Sheng Zeng
Janie Zhang
{"title":"Thank You to Reviewers 2026","authors":"","doi":"10.3322/caac.70108","DOIUrl":"https://doi.org/10.3322/caac.70108","url":null,"abstract":"<p>In order to maintain the high standards of <i>CA</i>’s content, the Editors of <i>CA</i> rely on the knowledge and dedication of many experts in deciding which topics to pursue, which manuscripts to publish, and what modifications to make to ensure medical and scientific accuracy and suitability for our readers. We thank our Associate Editors and our Editorial Advisory Board, who continue to provide these services for us time and time again.</p><p>We are also greatly indebted to the effort and expertise of the following individuals for reviewing manuscripts for the journal from July 1, 2025, to June 30, 2026. These individuals go beyond expectations by consistently and expeditiously delivering comprehensive, discerning reviews.</p><p>Nadeem R. Abu-Rustum</p><p>Pedro Barata</p><p>Surinder Batra</p><p>Beth Beadle</p><p>Daniel Benedetti</p><p>Sushil Beriwal</p><p>Stephanie Blank</p><p>Susana Campos</p><p>Fumiko Chino</p><p>Clay Cockerell</p><p>Adil Daud</p><p>Michael Davies</p><p>Ajay Dhakal</p><p>Jessica DiSilvestro</p><p>Milana Dolezal</p><p>Julien Edeline</p><p>Bita Esmaeli</p><p>Douglas Evans</p><p>Vaia Florou</p><p>Zhi Ven Fong</p><p>Anand Ganesan</p><p>Ben George</p><p>Amandeep Godara</p><p>Krishna Gunturu</p><p>Lindsay Hannan</p><p>Jeremy Harris</p><p>Kate Hetherington</p><p>Kathleen Horst</p><p>Fernando Hugo</p><p>Ahmedin Jemal</p><p>Rachel Jimenez</p><p>Corinne Joshu</p><p>Hina Khan</p><p>Albert E. Kim</p><p>Kevin B. Kim</p><p>Matthew Kudek</p><p>Matteo Lambertini</p><p>Phebe Lemert</p><p>Gilberto Lopes de Lima Lopes Junior</p><p>Stefano Luminari</p><p>Martin Ma</p><p>Kim Margolin</p><p>Carol Marquez</p><p>Jonathan Marron</p><p>Claudia Massarotti</p><p>Paul Mathew</p><p>Clarissa Mathias</p><p>Sandy Mazzoni</p><p>Krishnan Patel</p><p>Mack Roach</p><p>Ilana Schlam</p><p>Vivek Subbiah</p><p>Molly Taylor</p><p>Derek Tsang</p><p>Angela E. Usher</p><p>Hao Wang</p><p>Lori Wirth</p><p>Fabio Ynoe de Moraes</p><p>Youssef Zeidan</p><p>Mu-Sheng Zeng</p><p>Janie Zhang</p>","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 5","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70108","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849199","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}
Michael Rooney MD, MS, Krishnan R. Patel MD, MHS, Shalin Shah MD, Justin R. Gregg MD, Steven Jay Frank MD, Karen Hoffman MD, MHSc, MPH, Ryan Park MD, Comron J. Hassanzadeh MD, MPH, Seungtaek Choi MD, Sean McGuire MD, PhD, Quynh-Nhu Nguyen MD, Daniel N. Costa MD, Patricia Troncoso MD, Sumit K. Subudhi MD, Shuang George Zhao MD, PhD, Curtis A. Pettaway MD, Paul Corn MD, PhD, Chad Tang MD, Phuoc T. Tran MD, PhD
<p>A Black gentleman aged 67 years was referred for evaluation of an elevated prostate-specific antigen (PSA) level of 4.9 ng/mL detected during routine screening, representing an increase from a prior value of 3.6 ng/mL 1 year earlier and a gradual rise from values in the low 2 ng/mL range beginning in his mid-50s. He reported no lower urinary tract symptoms and had an Eastern Cooperative Oncology Group performance status of 0. His past medical history was notable only for well controlled hypertension and hyperlipidemia. He had no family history of prostate cancer. He remained physically active and had an estimated life expectancy exceeding 10 years based on actuarial life tables,<span><sup>1</sup></span> with both parents having lived into their late 80s. His American Urological Association International Prostate Symptom Score was 6, and his score on the Sexual Health Inventory for Men was 19. Digital rectal examination revealed subtle induration involving the right peripheral zone of the prostate without fixation.</p><p>Multiparametric magnetic resonance imaging (MRI) of the prostate demonstrated a 1.9-cm lesion characterized as a Prostate Imaging-Reporting and Data System score of 5 (<i>very high</i> likelihood of significant cancer). It was located within the right posterior peripheral zone at the mid-gland, without radiographic evidence of extracapsular extension or seminal vesicle invasion. No suspicious pelvic lymph nodes were identified.</p><p>Transrectal ultrasound–guided, systematic and MRI-targeted biopsies were subsequently performed. Pathologic sampling included a systematic 12-core biopsy sampling of the entire prostate, from which seven of 12 cores were positive. The biopsy was enhanced by MRI-informed targeting of the aforementioned lesion with a Prostate Imaging-Reporting and Data System score of 5 and yielded two of three positive cores. Of all biopsies, the highest Gleason score was 4 + 3 = 7, representing an intermediate grade and correlating to International Society of Urological Pathology (ISUP) grade group 3,<span><sup>2</sup></span> with pattern 4 in approximately 60% and no cribriform features. Perineural invasion was present, and overall tumor involvement ranged from 20% to 70% within positive cores. Based on these findings, the patient was staged with clinical T2b, N0, M0 (cT2bN0M0) disease.</p><p>According to National Comprehensive Cancer Network (NCCN) criteria, the patient was classified as having unfavorable intermediate-risk (UIR) prostate cancer based on the presence of ISUP grade group 3<span><sup>2</sup></span> adenocarcinoma and ≥50% of cores that were positive for cancer. Staging with prostate-specific membrane antigen–positron emission tomography demonstrated no evidence of nodal or distant metastatic disease.</p><p>The patient was evaluated in a multidisciplinary clinic and expressed interest in definitive radiation therapy (RT) over surgery. Given his UIR disease, standard management options included RT al
一位67岁的黑人男士在常规筛查中检测到前列腺特异性抗原（PSA）水平升高4.9 ng/mL，比一年前的3.6 ng/mL有所增加，并从50多岁开始的低2 ng/mL范围逐渐上升。患者无下尿路症状，东部肿瘤合作组评分0。既往病史中仅有高血压和高脂血症控制良好。他没有前列腺癌的家族史。根据精算生命表估计，他的预期寿命超过10年，父母都活到了80多岁。他的美国泌尿学会国际前列腺症状评分为6分，他的男性性健康量表得分为19分。直肠指检显示轻微硬结累及右前列腺外周区，未固定。前列腺多参数磁共振成像（MRI）显示一个1.9厘米的病变，前列腺成像报告和数据系统评分为5分（非常高的显著癌症可能性）。它位于腺体中部右侧后周区，未见囊外延伸或精囊侵犯的影像学证据。未发现可疑的盆腔淋巴结。随后进行经直肠超声引导，系统和mri靶向活检。病理取样包括对整个前列腺进行系统的12核活检取样，其中12核中有7核为阳性。前列腺成像报告和数据系统评分为5分的上述病变的mri靶向活检增强了活检，并产生了三个阳性核心中的两个。在所有活检中，最高Gleason评分为4 + 3 = 7，代表中等级别，与国际泌尿病理学学会（ISUP）分级3,2组相关，约60%为4型，无筛状特征。存在神经周围浸润，阳性核区肿瘤总体受累范围为20%至70%。根据这些发现，患者被分期为临床T2b， N0, M0 （cT2bN0M0）疾病。根据国家综合癌症网络（NCCN）标准，基于ISUP级32组腺癌的存在和≥50%的核心癌阳性，患者被归类为不良中危（UIR）前列腺癌。前列腺特异性膜抗原的分期-正电子发射断层扫描显示没有淋巴结或远处转移性疾病的证据。患者在多学科临床评估，并表示对最终放射治疗（RT）的兴趣超过手术。考虑到他的UIR疾病，标准的治疗方案包括单独RT或联合短期雄激素剥夺治疗（ADT）。然而，考虑到与激素治疗相关的潜在代谢、性和生活质量（QoL）影响，患者特别感兴趣的是了解添加ADT是否会有意义地改善他的预后。他还对癌症复发和与癌症有关的死亡表示严重关切，这是基于他以前照顾患有癌症的家庭成员的经验，以及这给他的大家庭带来的情感和后勤负担。为了进一步完善治疗选择，进行了分子生物标志物检测。在多个临床队列中，Decipher前列腺基因组分类器（Decipher GC）的评分为0.94（图1），3-7对应于高基因组风险，这与远处转移（DM）和前列腺癌特异性死亡率（PCSM）的风险增加有关。相比之下，使用Artera多模态人工智能（MMAI）平台（ArteraAI）进行分析，该平台将数字组织病理学特征与临床变量相结合，预测转移风险较低，并在短期ADT （ST-ADT）预测生物标志物成分方面得出阴性结果（图2）因此，这两种生物标志物提供了不一致的临床指导。Decipher结果提示该疾病具有生物侵袭性，并支持强化治疗，而MMAI预测模型提示单独RT与RT加ST-ADT相似，提示ST-ADT的增量益处可能很小。在这篇文章中，我们对越来越常见的中危局限性前列腺癌（IR-PCa）的临床表现进行了广泛的概述，其中生物标志物指导是不一致的。我们的目标是针对临床医生提供商业上可获得的、指南认可的生物标志物测试的高层次讨论，以帮助那些在实践中理解如何将这些下一代测试整合到他们的临床实践中。 我们概述了目前可用的证据以及在现代临床实践中使用这些生物标志物的知识差距，试图总结我们对IR-PCa的机构实践。我们有目的地概述了一个在局限性前列腺癌的两种常见生物标志物之间存在极端分歧的案例，以突出一个需要更多证据的实质性实践不确定性领域，我们讨论了通过这种介绍进行推理的几个潜在框架。对于局限性前列腺癌患者，ADT是决定性放疗的辅助手段。多个3期随机试验表明，有限时间的ADT改善了RT在多个终点的疗效。然而，根据基线疾病风险，绝对获益的幅度有很大差异，这就产生了关于哪些患者从强化治疗中获得有意义的临床获益的持续争论。ST-ADT（即≤6个月）在IR-PCa中的作用是通过几项随机试验确定的放射治疗肿瘤学组的3期研究RTOG 94084将2000多名主要患有IR-PCa的男性随机分配到有或没有4个月ADT的放疗组。在10年的随访中，PCSM有统计学上显著的益处，转化为总生存期（OS）的改善值得注意的是，这种益处是在整个研究人群中观察到的，并且主要是由IR-PCa人群驱动的，因为在低风险人群中缺乏益处。在长期随访中，DM （ir -亚组的风险比[HR]， 0.67; p = 0.01）和PCSM （ir -亚组的风险比[HR]， 0.53; p < 0.01）方面的获益持续存在，尽管由于长期随访中非前列腺癌死亡，OS出现相似。最近，NRG Oncology/RTOG 0815 iii期试验在现代使用现代剂量递增放疗（即≥75灰色）重新审视了这个问题与RTOG 9408相反，在RTOG 0815中，试验患者被随机分配到有或没有6个月ADT的RT组，患者人群仅限于那些患有IR-PCa的患者。在RTOG 0815中，ADT与生化衰竭时间的改善（原因特异性HR， 0.52; p < .001）、DM（原因特异性HR， 0.25; p < .001）和PCSM（原因特异性HR， 0.10; p = .007）相关，转化为10年这些临床终点的估计绝对改善分别为8%、4%和2%。尽管在PCSM中获益，并且在非PCSM中没有相应的恶化（HR, 0.92; p = 0.56），但该试验未能证明在OS方面获益（HR, 0.85; p = 0.22）。这可能反映了在大多数死亡发生于非前列腺癌的竞争原因11和/或复发疾病治疗的改进的人群中，对OS的治疗效果估计的精确度有限。除了RTOG 9408和RTOG 0815之外，还有另外5项随机试验评估了外束放疗加或不加ST-ADT的益处。4,5,12 -14他们证明，在患有IR-PCa的人群中，ADT可以改善临床有意义的终点虽然这对于平均风险的IR-PCa患者是正确的，但IR-PCa包含了广泛的预后范围以及对ADT的敏感性，只有一些亚组获得了有意义的益处，例如临床患有UIR疾病的患者。鉴于ADT的不良反应，包括代谢功能障碍、心血管风险、性功能障碍和生活质量下降，人们越来越关注用下一代生物标志物来指导患者选择ADT。下面，我们讨论生物标志物评估如何为考虑ST-ADT强化的IR-PCa患者提供患者咨询。将分子和计算生物标志物整合到前列腺癌管理中，为治疗个性化带来了新的机会，但也带来了新的临床挑战。当不同的生物标志物平台在治疗选择方面提供不一致的指导时，就会出现这样的挑战，正如我们的案例所强调的那样。因此，了解这些工具之间的生物学和方法学差异对于在临床实践中解释其结果至关重要。破译GC主要被证明是一种独立的预后生物标志物，超越了传统的临床病理因素。基因组风险评分高的患者患糖尿病和PCSM的比例一直较高，支持将其作为识别生物侵袭性疾病的工具。相比之下，ArteraAI MMAI测试平台不仅代表了一种预后生物标志物分析，而且代表了一种预测性生物标志物成分。 具体来说，预测性生物标志物旨在识别更有可能从ST-ADT添加到RT中获得有意义的益
{"title":"Discordant molecular biomarkers in unfavorable intermediate-risk localized prostate cancer","authors":"Michael Rooney MD, MS, Krishnan R. Patel MD, MHS, Shalin Shah MD, Justin R. Gregg MD, Steven Jay Frank MD, Karen Hoffman MD, MHSc, MPH, Ryan Park MD, Comron J. Hassanzadeh MD, MPH, Seungtaek Choi MD, Sean McGuire MD, PhD, Quynh-Nhu Nguyen MD, Daniel N. Costa MD, Patricia Troncoso MD, Sumit K. Subudhi MD, Shuang George Zhao MD, PhD, Curtis A. Pettaway MD, Paul Corn MD, PhD, Chad Tang MD, Phuoc T. Tran MD, PhD","doi":"10.3322/caac.70105","DOIUrl":"10.3322/caac.70105","url":null,"abstract":"<p>A Black gentleman aged 67 years was referred for evaluation of an elevated prostate-specific antigen (PSA) level of 4.9 ng/mL detected during routine screening, representing an increase from a prior value of 3.6 ng/mL 1 year earlier and a gradual rise from values in the low 2 ng/mL range beginning in his mid-50s. He reported no lower urinary tract symptoms and had an Eastern Cooperative Oncology Group performance status of 0. His past medical history was notable only for well controlled hypertension and hyperlipidemia. He had no family history of prostate cancer. He remained physically active and had an estimated life expectancy exceeding 10 years based on actuarial life tables,<span><sup>1</sup></span> with both parents having lived into their late 80s. His American Urological Association International Prostate Symptom Score was 6, and his score on the Sexual Health Inventory for Men was 19. Digital rectal examination revealed subtle induration involving the right peripheral zone of the prostate without fixation.</p><p>Multiparametric magnetic resonance imaging (MRI) of the prostate demonstrated a 1.9-cm lesion characterized as a Prostate Imaging-Reporting and Data System score of 5 (<i>very high</i> likelihood of significant cancer). It was located within the right posterior peripheral zone at the mid-gland, without radiographic evidence of extracapsular extension or seminal vesicle invasion. No suspicious pelvic lymph nodes were identified.</p><p>Transrectal ultrasound–guided, systematic and MRI-targeted biopsies were subsequently performed. Pathologic sampling included a systematic 12-core biopsy sampling of the entire prostate, from which seven of 12 cores were positive. The biopsy was enhanced by MRI-informed targeting of the aforementioned lesion with a Prostate Imaging-Reporting and Data System score of 5 and yielded two of three positive cores. Of all biopsies, the highest Gleason score was 4 + 3 = 7, representing an intermediate grade and correlating to International Society of Urological Pathology (ISUP) grade group 3,<span><sup>2</sup></span> with pattern 4 in approximately 60% and no cribriform features. Perineural invasion was present, and overall tumor involvement ranged from 20% to 70% within positive cores. Based on these findings, the patient was staged with clinical T2b, N0, M0 (cT2bN0M0) disease.</p><p>According to National Comprehensive Cancer Network (NCCN) criteria, the patient was classified as having unfavorable intermediate-risk (UIR) prostate cancer based on the presence of ISUP grade group 3<span><sup>2</sup></span> adenocarcinoma and ≥50% of cores that were positive for cancer. Staging with prostate-specific membrane antigen–positron emission tomography demonstrated no evidence of nodal or distant metastatic disease.</p><p>The patient was evaluated in a multidisciplinary clinic and expressed interest in definitive radiation therapy (RT) over surgery. Given his UIR disease, standard management options included RT al","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 4","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148811662","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}
<p>Few therapies are available for patients with previously treated metastatic pancreatic ductal adenocarcinomas (mPDACs), and those that exist offer limited benefit while causing toxic side effects. The median overall survival (OS) for patients with the disease is less than 1 year.</p><p>More than 90% of PDAC cases, including mPDAC, have mutations in the <i>KRAS</i> gene, and researchers have long sought a way to effectively target them. Although some targeted therapies for the mutation exist, they are limited to rare molecular subgroups.</p><p>Scientists have developed new types of <i>RAS</i>(ON) multiselective inhibitors to target a broader range of variants and to improve outcomes for patients with hard-to-treat cancers. In the phase 3 RASolute 302 trial, the <i>RAS</i>(ON) inhibitor daraxonrasib demonstrated significant, unprecedented improvements in both OS and progression-free survival (PFS) for patients with mPDAC.</p><p>The international phase 3 trial compared daraxonrasib to chemotherapy in 500 patients with mPDAC. Results showed nearly a doubling of survival with fewer side effects in patients treated with daraxonrasib versus chemotherapy.</p><p>“We have never seen survival like this before in patients with advanced pancreas cancer who have progressed on one line of chemotherapy, so it will absolutely be landscape-changing for therapeutic options,” says Rachna Shroff, MD, chief of the Division of Hematology/Oncology at the University of Arizona Cancer Center in Tucson. “This is a game changer for pancreas cancer.”</p><p>The research was presented at the 2026 American Society of Clinical Oncology Annual Meeting and was published simultaneously in <i>The New England Journal of Medicine</i> (doi:10.1056/NEJMoa2605555).</p><p>Daraxonrasib is an oral <i>RAS</i>(ON) multiselective, tricomplex inhibitor of the active guanosine triphosphate–bound state of mutant and wild-type <i>RAS</i>.</p><p>The open-label, randomized trial assigned patients previously treated for mPDAC to receive either once daily oral daraxonrasib or chemotherapy of the investigator’s choice. The dual primary endpoints were OS and PFS in the subpopulation of patients with <i>RAS</i> G12 mutations (91.8% of patients).</p><p>The overall study population included patients with <i>RAS</i> G12, G13, or Q61 mutations as well as those with no identified <i>RAS</i> mutation. Key secondary endpoints included OS and PFS in the overall population along with objective responses and patient-reported quality of life in the <i>RAS</i> G12 and overall populations. Investigators also assessed safety.</p><p>In the study population, 248 patients received daraxonrasib, and 252 patients received chemotherapy. For patients in the <i>RAS</i> G12 group, the median OS was 13.2 months with daraxonrasib and 6.6 months with chemotherapy. In the overall population, the median OS was 13.2 and 6.7 months, respectively. In both groups, the hazard ratio was 0.40 (<i>p</i> < .001).</p><p>For patients wi
{"title":"Daraxonrasib significantly improves overall and progression-free survival in patients with previously treated metastatic pancreatic cancer","authors":"Carrie Printz","doi":"10.3322/caac.70097","DOIUrl":"https://doi.org/10.3322/caac.70097","url":null,"abstract":"<p>Few therapies are available for patients with previously treated metastatic pancreatic ductal adenocarcinomas (mPDACs), and those that exist offer limited benefit while causing toxic side effects. The median overall survival (OS) for patients with the disease is less than 1 year.</p><p>More than 90% of PDAC cases, including mPDAC, have mutations in the <i>KRAS</i> gene, and researchers have long sought a way to effectively target them. Although some targeted therapies for the mutation exist, they are limited to rare molecular subgroups.</p><p>Scientists have developed new types of <i>RAS</i>(ON) multiselective inhibitors to target a broader range of variants and to improve outcomes for patients with hard-to-treat cancers. In the phase 3 RASolute 302 trial, the <i>RAS</i>(ON) inhibitor daraxonrasib demonstrated significant, unprecedented improvements in both OS and progression-free survival (PFS) for patients with mPDAC.</p><p>The international phase 3 trial compared daraxonrasib to chemotherapy in 500 patients with mPDAC. Results showed nearly a doubling of survival with fewer side effects in patients treated with daraxonrasib versus chemotherapy.</p><p>“We have never seen survival like this before in patients with advanced pancreas cancer who have progressed on one line of chemotherapy, so it will absolutely be landscape-changing for therapeutic options,” says Rachna Shroff, MD, chief of the Division of Hematology/Oncology at the University of Arizona Cancer Center in Tucson. “This is a game changer for pancreas cancer.”</p><p>The research was presented at the 2026 American Society of Clinical Oncology Annual Meeting and was published simultaneously in <i>The New England Journal of Medicine</i> (doi:10.1056/NEJMoa2605555).</p><p>Daraxonrasib is an oral <i>RAS</i>(ON) multiselective, tricomplex inhibitor of the active guanosine triphosphate–bound state of mutant and wild-type <i>RAS</i>.</p><p>The open-label, randomized trial assigned patients previously treated for mPDAC to receive either once daily oral daraxonrasib or chemotherapy of the investigator’s choice. The dual primary endpoints were OS and PFS in the subpopulation of patients with <i>RAS</i> G12 mutations (91.8% of patients).</p><p>The overall study population included patients with <i>RAS</i> G12, G13, or Q61 mutations as well as those with no identified <i>RAS</i> mutation. Key secondary endpoints included OS and PFS in the overall population along with objective responses and patient-reported quality of life in the <i>RAS</i> G12 and overall populations. Investigators also assessed safety.</p><p>In the study population, 248 patients received daraxonrasib, and 252 patients received chemotherapy. For patients in the <i>RAS</i> G12 group, the median OS was 13.2 months with daraxonrasib and 6.6 months with chemotherapy. In the overall population, the median OS was 13.2 and 6.7 months, respectively. In both groups, the hazard ratio was 0.40 (<i>p</i> < .001).</p><p>For patients wi","PeriodicalId":137,"journal":{"name":"CA: A Cancer Journal for Clinicians","volume":"76 4","pages":""},"PeriodicalIF":685.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784613","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}
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