Closer Look at Cutting-Edge Lung Cancer Surgery: How a New Study Could Change the Game for NSCLC Patients

Study Overview

This study was a multicentre, open-label, randomized, controlled, phase 3 trial, specifically a post-hoc supplemental analysis of the JCOG0802/WJOG4607L trial. It focused on patients aged between 20 and 85 years who had small-sized non-small-cell lung cancer (NSCLC) with a radiologically pure-solid appearance on thin-section CT, characterized by a consolidation tumor ratio of 1.0 and a maximum size of 2 cm (1). The primary objective was to investigate the reasons behind the superior overall survival rates observed in segmentectomy compared to lobectomy for this patient population, by analyzing survival rates, causes of death, and recurrence patterns.

The trial involved 553 patients, all of whom had radiologically pure-solid NSCLC. These participants were equally divided into two groups, with 274 undergoing lobectomy and 279 undergoing segmentectomy. The median age of the patients was 67 years, and the cohort consisted of 63% male and 37% female patients. Race and ethnicity data were not collected.

The results, as of June 13, 2020, after a median follow-up of 7.3 years, indicated a significant difference in the 5-year overall survival rate between the two groups. The segmentectomy group showed a higher survival rate of 92.4% (95% CI 88.6-95.0) with 38 deaths, compared to 86.1% (95% CI 81.4-89.7) with 55 deaths in the lobectomy group. This difference had a hazard ratio of 0.64 (95% CI 0.41-0.97; p=0.033). However, the 5-year relapse-free survival rates were similar between the groups: 82.0% (95% CI 76.9-86.0) in the segmentectomy group with 52 events, and 81.7% (95% CI 76.5-85.8) in the lobectomy group with 34 events, yielding a hazard ratio of 1.01 (95% CI 0.72-1.42; p=0.94).

Lung cancer-related deaths occurred in 7% of patients in both groups (20 in lobectomy and 19 in segmentectomy). Deaths due to other causes were higher in the lobectomy group (13%) compared to the segmentectomy group (7%). Notably, locoregional recurrence was higher following segmentectomy (21 [8%] vs 45 [16%]; p=0.0021). Subgroup analyses revealed that patients aged 70 years or older and male patients had better 5-year overall survival rates with segmentectomy compared to lobectomy. Conversely, better 5-year relapse-free survival after lobectomy was observed in patients younger than 70 years and in female patients.

The study concluded that segmentectomy offers improved overall survival in patients with pure-solid NSCLC compared to lobectomy, but these outcomes vary depending on the patient's age and sex. The findings suggest a need for further research to define clinically relevant indications for segmentectomy in this specific type of NSCLC. The study was funded by the Japanese National Cancer Center Research and Development Fund and other research grants from the Ministry of Health, Labor, and Welfare of Japan.

Standard Treatment

The current standard treatment for early-stage non-small-cell lung cancer (NSCLC), especially for small-sized tumors with a solid appearance on imaging, typically involves surgical resection. The most common surgical approaches are lobectomy (removal of an entire lobe of the lung) and, less frequently, sub-lobar resections like segmentectomy or wedge resection. Lobectomy has been considered the gold standard for early-stage NSCLC due to its effectiveness in completely removing the tumor and reducing the risk of recurrence.

The impact of the study in question, which compares segmentectomy and lobectomy for small-sized, pure-solid NSCLC, is significant for several reasons:

  1. Potential Paradigm Shift in Surgical Approach: The study's finding that segmentectomy leads to a higher overall survival rate than lobectomy for certain patient subgroups may influence surgical decision-making. If these findings are replicated and validated in further studies, they could lead to a shift towards segmentectomy being favored over lobectomy for selected patients with small-sized, pure-solid NSCLC.

  2. Consideration of Patient Characteristics: The study highlights the importance of considering patient-specific factors like age and sex in deciding the surgical approach. This aligns with the growing trend towards personalized medicine in oncology, where treatment decisions are increasingly tailored to individual patient characteristics.

  3. Balancing Effectiveness and Quality of Life: Segmentectomy, being less extensive than lobectomy, might offer advantages in terms of preserving lung function and potentially leading to a better quality of life post-surgery. This aspect is particularly important for elderly patients or those with compromised lung function.

  4. Need for Further Research: The study underscores the need for additional research to more precisely define which patients would benefit most from segmentectomy. It opens avenues for further investigation into the long-term outcomes of segmentectomy, especially regarding recurrence rates and quality of life.

  5. Impact on Clinical Guidelines: Depending on the strength of evidence from this and subsequent studies, there could be changes to clinical guidelines recommending segmentectomy as a preferred option for certain patient groups with NSCLC.

In conclusion, while the results of this study are promising and suggest a potential shift in surgical treatment for a subset of NSCLC patients, it is crucial to approach these findings with caution. Further research, including larger randomized controlled trials, is needed to confirm these results and to better understand the long-term implications of segmentectomy versus lobectomy in NSCLC treatment. As of now, lobectomy remains the standard treatment, but this study contributes to the evolving landscape of surgical options for lung cancer.

Clinical Impact Potential

The clinical impact potential of this trial can be assessed as medium. This assessment is based on several considerations:

  1. Targeted Patient Population: The study is focused on a specific subset of NSCLC patients - those with small-sized, pure-solid tumors. While this represents a significant group within lung cancer patients, the findings may not be applicable to all NSCLC cases, particularly those with different tumor characteristics or at a more advanced stage.

  2. Potential for Surgical Practice Change: The study suggests that segmentectomy may offer better overall survival rates than lobectomy for certain patients, which could lead to a change in surgical practices. However, lobectomy remains the standard of care, and this study alone may not be sufficient to shift the paradigm entirely. It does, however, contribute to the growing body of evidence that could gradually change clinical guidelines.

  3. Need for Further Validation: The findings, while promising, require validation through additional studies. The medium impact is partly due to the need for further research to confirm these results and understand the long-term implications fully.

  4. Balance of Outcomes: The study raises important considerations about balancing overall survival with other factors like relapse-free survival and the rate of locoregional recurrence. These factors are crucial in determining the best surgical approach for individual patients.

  5. Alignment with Personalized Medicine Trends: The findings align with the trend towards more personalized approaches in cancer treatment, considering patient-specific factors. This is increasingly important in oncology but requires a nuanced understanding of when to apply different treatment strategies.

In summary, the trial has the potential to moderately impact clinical practice, particularly in how surgeons choose between lobectomy and segmentectomy for specific NSCLC patients. However, its impact is not yet high due to the need for further studies and validation, along with its applicability to a specific patient subgroup rather than the broader NSCLC population.

Reference

Hattori A, Suzuki K, Takamochi K, Wakabayashi M, Sekino Y, Tsutani Y, Nakajima R, Aokage K, Saji H, Tsuboi M, Okada M, Asamura H, Nakamura K, Fukuda H, Watanabe SI; Japan Clinical Oncology Group; West Japan Oncology Group. Segmentectomy versus lobectomy in small-sized peripheral non-small-cell lung cancer with radiologically pure-solid appearance in Japan (JCOG0802/WJOG4607L): a post-hoc supplemental analysis of a multicentre, open-label, phase 3 trial. Lancet Respir Med. 2024 Jan 3:S2213-2600(23)00382-X. doi: 10.1016/S2213-2600(23)00382-X. Epub ahead of print. PMID: 38184010.