The Rounds Report: September 2025
The surgeon walked into the room and told the patient to cancel their colectomy. Not because of complications or delays—because they were already cured.
This isn't science fiction. It happened 80 times this summer in a groundbreaking dostarlimab study, and it's just one of five paradigm-shifting trials that published between June and September.
Here's what caught my attention during this quarter's literature analysis: these aren't incremental improvements or "promising early results." These are studies that just might fundamentally challenge the treatment algorithms we learned in residency. Cancer patients skipping surgery. COPD finally getting targeted therapy. Kidney disease responding to combination approaches we thought were too risky.
The medical Twitter debates are already fierce, department meetings are getting longer, and some of these findings are so practice-changing that updated guidelines are dropping before the ink is dry on the publications.
Five studies. Five paradigm shifts. Let me walk you through what matters most.
The Big Five Game-Changers
1. Surgery-Free Cancer Cures Are Now Reality
Remember when cancer diagnosis meant immediate surgery planning? The dostarlimab organ preservation study just proved 82% of patients can skip surgery entirely and stay cured.
The results from 117 patients with mismatch repair-deficient tumors are revolutionary: 80% avoided their planned surgeries completely, including colectomies, gastrectomies, and pancreaticoduodenectomies. Most remarkably, all 49 rectal cancer patients achieved complete responses with 92% remaining recurrence-free at 2 years.
This isn't limited to one cancer type. The study included gastroesophageal, hepatobiliary, genitourinary, and gynecologic cancers. The FDA granted breakthrough therapy designation, with expanded access programs already available.
Bottom line: Universal dMMR/MSI screening is now essential. That rectal cancer patient you're seeing tomorrow might qualify for a cure without surgery.
2. Kidney Disease Gets Its First Combination Breakthrough
The CONFIDENCE trial proved that 1+1 equals 3 in chronic kidney disease. Simultaneous finerenone plus empagliflozin achieved a 52% reduction in urinary albumin-to-creatinine ratio compared to either drug alone.
Among 800 participants, combination therapy was 29% more effective than finerenone alone and 32% more effective than empagliflozin alone (both P<0.001). This challenges the traditional sequential approach we've been using for decades.
Both medications are already FDA-approved for this population, enabling immediate implementation. The magnitude of UACR reduction predicts substantial long-term kidney and cardiovascular protection.
Clinical reality check: Start dual therapy conversations now with appropriate CKD patients. Monitor potassium and eGFR as usual, but combination initiation is safe and significantly more effective.
3. COPD Finally Gets Its First Biologic
After decades without disease-modifying therapies, the MATINEE trial established mepolizumab as the first biologic approved for COPD. Results show 21% reduction in moderate/severe exacerbations (RR 0.79, P=0.01) in patients with blood eosinophils ≥300 cells/μL.
Among 804 patients on triple inhaled therapy, time to first exacerbation improved from 321 to 419 days, with 35% reduction in ED visits and hospitalizations. This breakthrough addresses 20-40% of COPD patients with eosinophilic phenotypes who remain inadequately controlled.
FDA approval occurred May 22, 2025, making this immediately available. The simple biomarker requirement (blood eosinophil count ≥150 cells/μL) enables straightforward patient selection using routine CBC testing.
Practice implication: Start checking eosinophil counts in exacerbating COPD patients. This represents a historic milestone comparable to early biologic approvals in asthma.
4. COVID Prevention Breakthrough for Cancer Patients
The interferon-alpha nasal spray study delivered what oncologists have been hoping for: 40% reduction in COVID-19 infection risk (RR 0.60, 95% CI 0.33-0.97) among cancer patients.
Among 433 cancer patients, infection rates dropped from 14.4% (placebo) to 8.3% (interferon-alpha), with greatest efficacy in patients <65 years, women, and vaccinated individuals. This represents the first proven prophylactic intervention beyond vaccination and monoclonal antibodies.
Using commercially available interferon-alpha formulated as nasal spray, this intervention is immediately implementable in high-risk populations. The University of Melbourne/Peter MacCallum study provides level 1 evidence for protecting vulnerable patients.
What this means: Internal medicine physicians managing cancer patients now have an evidence-based prophylactic option during vulnerable treatment periods.
5. Lung Cancer Gets a New Gold Standard
The MARIPOSA study final analysis established amivantamab-lazertinib as the new first-line standard for EGFR-mutated NSCLC. Among 1,074 patients, combination therapy achieved progression-free survival of 23.7 vs 16.6 months compared to osimertinib (HR 0.70, P<0.001).
This chemotherapy-free regimen represents a paradigm shift in advanced lung cancer treatment. The combination showed particular benefit in high-risk patients with TP53 mutations, detectable ctDNA, or brain/liver metastases.
FDA/EMA approval occurred in 2024-2025, making this immediately available. Prophylactic measures during the first four months significantly reduce skin reactions and thrombotic events.
Clinical reality check: The subcutaneous formulation under investigation will improve convenience. Overall survival benefits are projected to exceed one year.
The Clinical Pearls That Matter
Baxdrostat breakthrough for resistant hypertension. The aldosterone synthase inhibitor baxdrostat achieved 9.8 mmHg placebo-adjusted reduction in systolic BP among patients with treatment-resistant hypertension. This represents the first novel mechanism in hypertension therapy in over two decades, targeting aldosterone dysregulation directly. BaxHTN trial results
Omega-3 fatty acids protect against childhood myopia. Higher dietary omega-3 intake was associated with shorter axial length and reduced myopia risk in over 1,000 children aged 6-8 years. Conversely, high saturated fat intake increased risk. The protective effect may work through improved choroidal blood flow preventing scleral hypoxia. Hong Kong Children Eye Study
Updated pneumococcal susceptibility changes antibiotic selection. S. pneumoniae isolates with penicillin MIC ≤2 μg/mL should be considered susceptible for respiratory tract infections (excluding meningitis). This updated breakpoint means oral β-lactams like amoxicillin are appropriate first-line therapy. Updated EUCAST breakpoints 2025
Semaglutide demonstrates vascular benefits beyond diabetes. The STRIDE trial shows semaglutide 1mg weekly improves walking capacity by clinically meaningful amounts (>20 meters) in PAD patients with type 2 diabetes, with 13% improvement in maximum walking distance. STRIDE trial results
Monday Morning Rounds: 5 Key Discussion Points
1. The surgery-free cancer revolution - Dostarlimab achieved 82% complete responses in mismatch repair-deficient tumors, enabling 80% of patients to avoid planned surgeries entirely.
2. CKD combination therapy breakthrough - The CONFIDENCE trial showed 52% better kidney protection with simultaneous finerenone plus empagliflozin versus sequential treatment.
3. COPD gets its first biologic - Mepolizumab reduced exacerbations by 21% in eosinophilic COPD patients, representing the first targeted therapy for this population.
4. COVID protection for cancer patients - Interferon-alpha nasal spray reduced COVID-19 infections by 40% in immunocompromised cancer patients.
5. Lung cancer treatment evolution - MARIPOSA study established amivantamab-lazertinib as the new first-line standard, improving survival by 7+ months versus osimertinib.
Before You Go...
This quarter delivered breakthrough research that challenges conventional approaches across multiple subspecialties. From surgery-free cancer cures to the first biologic for COPD, these studies represent evidence-based paradigm shifts with immediate clinical applications.
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Modern medicine is evolving toward precision approaches that target specific patient phenotypes. The question isn't whether these breakthroughs will influence your practice—it's how quickly you'll integrate them to optimize patient outcomes.
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Essential Reading for Deep Dives
Oncology Breakthroughs: • Dostarlimab Organ Preservation Study • MARIPOSA - Amivantamab-Lazertinib vs Osimertinib
Nephrology & Pulmonology Advances: • CONFIDENCE Trial - Dual CKD Therapy • MATINEE Trial - Mepolizumab for COPD
Infectious Disease Innovation: • Interferon-Alpha Nasal Spray for Cancer Patients • Updated EUCAST Antimicrobial Breakpoints 2025
Precision Medicine Applications: • STRIDE Trial - Semaglutide for PAD • FDA Approval - Mepolizumab for COPD
Disclaimer: The content provided in The Rounds Report is for educational and informational purposes only and does not constitute medical advice, diagnosis, treatment recommendations, or professional medical guidance. This newsletter presents summaries and analysis of published medical research and should not be used as a substitute for professional medical judgment, clinical decision-making, or consultation with qualified healthcare providers. Always consult with appropriate medical professionals and refer to original research sources before making any clinical decisions. The Rounds Report does not establish a doctor-patient relationship and readers should not rely on this content for patient care decisions.