adenocarcinoma

Importance Globally, 968 350 new cases and 659 853 deaths from gastric cancer were reported in 2022. In the US, 30 300 new cases and 10 780 deaths were estimated in 2025.

Observations Gastric cancer is more common in men, and the median age at diagnosis is 68 years. Most gastric cancers (>90%) are adenocarcinomas. Worldwide, 85% of cases arise from the stomach body or antrum and 15% from the cardia. In the US, more than 90% of patients diagnosed with gastric cancer present with symptoms such as weight loss and abdominal pain. At presentation, approximately 13% have localized disease (limited to the stomach), 15% to 25% have locally advanced disease, defined as a tumor that has spread to regional lymph nodes, and 35% to 65% have metastatic disease. Helicobacter pylori infection is a treatable risk factor associated with 90% of gastric body and antrum cancers globally. Additional modifiable risk factors include smoking, alcohol, obesity, and salt intake. In countries with high incidence such as Japan and Korea, routine endoscopic screening beginning at age 40 years is associated with improved survival. Diagnosis is made by endoscopic biopsy. Patients with localized gastric cancer are treated with surgical resection and have a 5-year relative survival rate of 75% with treatment. Patients with more advanced-stage disease should receive gastrectomy, perioperative chemotherapy with 5-fluorouracil, oxaliplatin, and docetaxel and immunotherapy (durvalumab). Metastatic or unresectable disease may be treated with chemotherapy, immunotherapy, and/or targeted therapy depending on biomarkers, including programmed cell death ligand 1 (PD-L1), human epidermal growth factor receptor 2 (ERBB2; formerly HER2 or HER2/neu), and claudin-18, isoform 2 (CLDN18.2). For PD-L1–expressing gastric cancer, adding immune checkpoint inhibitors, such as nivolumab and pembrolizumab, is associated with an additional 3 months of survival when compared with chemotherapy alone. For gastric cancers overexpressing the ERBB2 or CLDN18.2 proteins, the addition of trastuzumab or zolbetuximab, respectively, is associated with an additional 3 to 4 months’ survival. Early supportive care focusing on symptom management and on nutritional and psychosocial support is associated with 3 months of survival benefit. Less than 10% of patients with metastatic gastric cancer survive more than 5 years.

Conclusions and Relevance Approximately 30 300 new cases of gastric cancer are diagnosed annually in the US. Localized gastric cancer is treated with gastrectomy, and locally advanced disease is treated with surgery and chemoimmunotherapy. For patients with unresectable or metastatic gastric cancer, chemotherapy with immune checkpoint inhibitors and targeted therapies such as trastuzumab or zolbetuximab improves survival by several months.

Author/s:

Anuj Kishor Patel, Nilay S. Sethi

Lung Cancer in Nonsmoking Individuals: A Review

Megan George — Tue, 02 Dec 2025 15:53:35 +0000

Date Added:

December 2, 2025

Journal/Publication:

JAMA

Publication Date:

October 20, 2025

URL:

Lung Cancer in Nonsmoking Individuals: A Review

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1001/jama.2025.17695

Keywords

Early Detection of Cancer

PMID (1):

41114991

MeSH

Adenocarcinoma* / diagnosis

Adenocarcinoma* / epidemiology

Adenocarcinoma* / genetics

Adenocarcinoma* / therapy

Anaplastic Lymphoma Kinase / genetics

Carcinoma

Adenosquamous* / diagnosis

Adenosquamous* / epidemiology

Adenosquamous* / genetics

Adenosquamous* / therapy

Squamous Cell* / diagnosis

Squamous Cell* / epidemiology

Squamous Cell* / genetics

Squamous Cell* / therapy

Chemoradiotherapy

Adjuvant / methods

Early Detection of Cancer / standards

ErbB Receptors / genetics

Lung Neoplasms* / diagnosis

Lung Neoplasms* / epidemiology

Lung Neoplasms* / genetics

Lung Neoplasms* / therapy

male

Mass Screening / standards

Mutation

Neoplasm Staging

Non-Smokers* / statistics & numerical data

Pneumonectomy

practice guidelines as topic

Receptor Protein-Tyrosine Kinases / antagonists & inhibitors

Receptor Protein-Tyrosine Kinases / genetics

risk factors

Sex Factors

Small Cell Lung Carcinoma* / diagnosis

Small Cell Lung Carcinoma* / epidemiology

Small Cell Lung Carcinoma* / genetics

Small Cell Lung Carcinoma* / therapy

Smoking / adverse effects

tomography

X-Ray Computed / standards

Tyrosine Kinase Inhibitors / therapeutic use

A review of current knowledge regarding lung cancer in non-smokers. James W. Mold, MD, MPH

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Importance: Lung cancer in nonsmoking individuals (defined as people who have smoked fewer than 100 cigarettes in their lifetime) accounts for 15% to 20% of all lung cancer cases worldwide. In the US, the annual incidence of lung cancer in nonsmoking individuals is 14.4 to 20.8 per 100 000 person-years in females and 4.8 to 12.7 per 100 000 person-years in males.

Observations: Most lung cancers in nonsmoking individuals are histologically adenocarcinomas (60%-80%) with the remainder being squamous or adenosquamous (10%-20%) and rarely small cell lung cancer (<10%). Risk factors include exposure to passive smoking, radon exposure, air pollution, asbestos, and history of lung cancer in a first-degree family member. Therapeutically targetable genomic variants, such as EGFR mutations or ALK gene rearrangements, are more common in tumors from nonsmoking individuals compared with those with a smoking history (defined as people who currently or formerly smoked) (43% vs 11% for EGFR and 12% vs 2% for ALK). In contrast, tumor mutation burden, the number of somatic mutations in a tumor cell, is lower in lung cancer among nonsmoking individuals (0-3 mutations/megabase [Mb] vs 0-30 mutations/Mb). Similar to individuals with a history of smoking, nonsmoking individuals with lung cancer may present with wheeze, chest pain, dyspnea, hemoptysis, or symptoms attributable to metastatic disease (eg, bone pain and headache) or be diagnosed with incidentally detected disease. The US Preventive Services Task Force does not currently recommend lung cancer screening with low-dose computed tomographic scans for nonsmoking individuals, although screening guidelines vary globally. Treatment typically involves a combination of surgery, radiotherapy, and systemic therapies depending on stage, performance status, and molecular features of the tumor. Comprehensive next-generation sequencing should be performed on stage Ib to IIIa lung cancer tumor tissue from nonsmoking individuals because actionable genomic alterations, such as EGFR mutations or ALK gene rearrangements, are treated with targeted therapy such as the tyrosine kinase inhibitors osimertinib or lorlatinib, respectively. Median survival among nonsmoking individuals with advanced non-small cell lung cancer (stage IIIb or higher) and actionable genomic alterations can exceed 3 to 5 years, while survival without these genomic alterations is similar to lung cancer in people with a history of smoking (1-2 years).

Conclusions: Lung cancer in nonsmoking individuals accounts for 15% to 20% of lung cancer cases worldwide. Among patients with lung cancer, nonsmoking individuals are more likely to have genomic alterations such as EGFR mutations or ALK gene rearrangements, and these patients have improved survival when treated with tyrosine kinase inhibitors compared with chemotherapy.

Author/s:

Cian Murphy, Tej Pandya, Charles Swanton

Prostate Cancer: A Review

Erin Blanchette — Wed, 12 Mar 2025 21:19:16 +0000

Date Added:

March 12, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 10, 2025

URL:

Prostate Cancer: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.0228

Keywords

prostate

prostate cancer

adenocarcinoma

PMID (1):

40063046

MeSH

Prostate-Specific Antigen

An evidence-based review of our current understanding of prostate cancer. James W. Mold, MD, MPH

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Importance: Prostate cancer is the most common nonskin cancer in men in the US, with an estimated 299 010 new cases and 35 250 deaths in 2024. Prostate cancer is the second most common cancer in men worldwide, with 1 466 680 new cases and 396 792 deaths in 2022.

Observations: The most common type of prostate cancer is adenocarcinoma (≥99%), and the median age at diagnosis is 67 years. More than 50% of prostate cancer risk is attributable to genetic factors; older age and Black race (annual incidence rate, 173.0 cases per 100 000 Black men vs 97.1 cases per 100 000 White men) are also strong risk factors. Recent guidelines encourage shared decision-making for prostate-specific antigen (PSA) screening. At diagnosis, approximately 75% of patients have cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Based on risk stratification that incorporates life expectancy, tumor grade (Gleason score), tumor size, and PSA level, one-third of patients with localized prostate cancer are appropriate for active surveillance with serial PSA measurements, prostate biopsies, or magnetic resonance imaging, and initiation of treatment if the Gleason score or tumor stage increases. For patients with higher-risk disease, radiation therapy or radical prostatectomy are reasonable options; treatment decision-making should include consideration of adverse events and comorbidities. Despite definitive therapy, 2% to 56% of men with localized disease develop distant metastases, depending on tumor risk factors. At presentation, approximately 14% of patients have metastases to regional lymph nodes. An additional 10% of men have distant metastases that are associated with a 5-year survival rate of 37%. Treatment of metastatic prostate cancer primarily relies on androgen deprivation therapy, most commonly through medical castration with gonadotropin-releasing hormone agonists. For patients with newly diagnosed metastatic prostate cancer, the addition of androgen receptor pathway inhibitors (eg, darolutamide, abiraterone) improves survival. Use of abiraterone improved the median overall survival from 36.5 months to 53.3 months (hazard ratio, 0.66 [95% CI, 0.56-0.78]) compared with medical castration alone. Chemotherapy (docetaxel) may be considered, especially for patients with more extensive disease.

Conclusions and relevance: Approximately 1.5 million new cases of prostate cancer are diagnosed annually worldwide. Approximately 75% of patients present with cancer localized to the prostate, which is associated with a 5-year survival rate of nearly 100%. Management includes active surveillance, prostatectomy, or radiation therapy, depending on risk of progression. Approximately 10% of patients present with metastatic prostate cancer, which has a 5-year survival rate of 37%. First-line therapies for metastatic prostate cancer include androgen deprivation and novel androgen receptor pathway inhibitors, and chemotherapy for appropriate patients.

Author/s:

Ruben Raychaudhuri, Daniel W Lin, R Bruce Montgomery