Transbronchial Lung Cryobiopsy and Awake Video-Assisted Thoracic Surgery in Interstitial Lung Disease: Complementary Roles in a Stepwise Diagnostic Approach

The diagnostic evaluation of interstitial lung diseases (ILDs) remains challenging when clinical assessment and imaging findings are inconclusive. Although surgical lung biopsy has traditionally represented the diagnostic gold standard, its invasiveness and perioperative risks limit its applicability, particularly in patients with advanced disease or impaired respiratory reserve. This review aims to examine the evolving roles of transbronchial lung cryobiopsy (TBLC) and awake video-assisted thoracoscopic surgery (Awake VATS) within contemporary diagnostic pathways for ILD. A narrative review of the current literature was performed, focusing on studies evaluating the diagnostic performance, safety profiles, clinical indications, and complementary integration of TBLC and Awake VATS in patients with suspected ILD. Evidence from multidisciplinary ILD referral centers and recent guideline recommendations was critically analyzed. TBLC has progressively emerged as an appropriate first-line histological procedure in many ILD centers, providing a pooled diagnostic yield of approximately 80% with an acceptable safety profile. Awake VATS has refined the surgical approach by preserving spontaneous ventilation while maintaining high diagnostic accuracy. Current evidence suggests that these techniques should be considered complementary rather than competitive. A TBLC-first strategy, followed by selective surgical escalation when endoscopic sampling is non-diagnostic or insufficient, appears to achieve diagnostic accuracy comparable to upfront surgical biopsy while reducing complications, length of hospital stay, and overall patient burden. The choice between Awake VATS and conventional surgical biopsy should be individualized according to patient characteristics, institutional expertise, and available resources. TBLC and Awake VATS represent complementary tools within a multidisciplinary, personalized, and risk-adapted diagnostic framework for ILD. Their integrated use enables optimization of diagnostic accuracy while minimizing procedural invasiveness and improving patient safety, supporting a stratified approach to histological assessment in contemporary clinical practice.