A new large-scale study published in JAMA Network has revealed significant inaccuracies in the initial staging of pancreatic ductal adenocarcinoma (PDAC), with the majority of early-stage patients being upstaged following surgical resection and histopathological examination.
Widespread Understaging in Clinical Practice
The research, analyzing data from 24,260 patients with complete records in the National Cancer Database between 2004 and 2020, found that 78.4% of patients initially diagnosed with stage I PDAC and 29.2% with stage II disease were upstaged following histopathological examination. Most notably, the majority of stage I patients were upstaged to stage IIB, suggesting that undetected lymph node involvement is the primary factor in clinical understaging.
Treatment Approaches and Staging Accuracy
The study examined two primary treatment pathways: upfront surgical resection (USR) and neoadjuvant therapy followed by surgical resection (NTSR). Among patients receiving USR, 79.1% were upstaged, compared to 73.5% in the NTSR group. Dr. Gerardo Perrotta, a post-doctoral research fellow at Cedars-Sinai and lead researcher, noted that "the proportions upstaged were lower in the NTSR group than the USR group, suggesting that the additional time required for neoadjuvant therapy did not contribute to disease progression."
Detailed Patient Demographics and Outcomes
The study population had a median age of 60 years, with 51% being women. For stage I PDAC patients, the disease distribution was:
- Stage IA: 9.3%
- Stage IB: 15.5%
- Stage IIA: 16.9%
- Stage IIB: 48.8%
- Stage III: 7.9%
- Stage IV: 1.6%
The mean time from diagnosis to surgery varied significantly between treatment approaches: 25 days for USR versus 153 days for NTSR (P <.001).
Historical Trends and Current Implications
Analysis of staging accuracy over different time periods revealed persistent challenges. For stage I patients, upstaging rates were:
- 2006-2010: 69.5%
- 2011-2017: 82.7%
- 2018-2020: 75.4%
These findings highlight an ongoing challenge in accurate initial staging, despite advances in diagnostic technologies. The research team emphasized that clinical staging has been a poor predictor of pathologic staging, consistently overrepresenting earlier stages.
Study Limitations and Future Directions
While comprehensive, the study had several limitations, including:
- Lack of information on preoperative imaging
- Absence of data on factors influencing treatment decisions
- No clinical outcome data for upstaged patients
- Limited information on resectability criteria
These findings underscore the need for more accurate initial staging methods and suggest that current clinical staging practices may need reassessment to improve treatment planning and patient outcomes in early-stage PDAC.
