Jump to content

Stage III Surgery clarified!


Recommended Posts

Role of Surgery in Stage III NSCLC Clarified

By Charles Bankhead, Staff Writer, MedPage Today

Published: July 27, 2009

Reviewed by Zalman S. Agus, MD; Emeritus Professor

University of Pennsylvania School of Medicine and

Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner Earn CME/CE credit

for reading medical news

HOUSTON, July 27 -- Concurrent chemoradiation followed by surgery improves progression-free but not overall survival in patients with stage III non-small cell lung cancer (NSCLC) compared with chemotherapy and definitive radiation, a cooperative group clinical trial showed.

Action Points

* Explain to patients that surgery after chemoradiation improved progression-free survival but not overall survival in stage III non-small cell lung cancer.

* An unplanned analysis showed that less extensive surgery (lobectomy versus pneumonectomy) improved overall survival.

Subgroup analysis showed that surgery did improve overall survival when lobectomy was performed, as opposed to pneumonectomy, Kathy Albain, MD, of Loyola University Chicago in Mayfield, Ill., and colleagues reported online in The Lancet.

Taken together, the results indicate that either therapeutic strategy is an option for patients with stage III NSCLC and ipsilateral mediastinal nodal metastases (N2).

"A prospective trial is unlikely to be done to validate the hypothesis generated as a result of our exploratory analysis [of lobectomy]," the authors concluded. "Thus, medically healthy patients with stage IIIA(N2) non-small cell lung cancer should be assessed by a team skilled in multimodality treatment, and treatment options can be considered during assessment.

"On the basis of the findings of our study, patients should be counseled about the risks and potential benefits of definitive chemotherapy plus radiotherapy with and without a surgical resection (preferably by lobectomy)."

Progressive clinical-trial evaluation showed that concurrent chemoradiation improved survival in stage IIIA(N2) NSCLC compared with surgery or radiotherapy alone.

Several pilot studies suggested that surgery after chemoradiation optimized local control. However, the results sparked controversy because long-term survival was higher than expected, the authors said.

Moreover, the studies of trimodal therapy demonstrated substantial toxicity, postoperative morbidity, and mortality.

The studies also were criticized because of patients' clinical heterogeneity and because the patients seemed unusually healthy compared with the general population of stage III NSCLC.

Two additional phase II studies showed favorable outcomes in stage III NSCLC patients: one employing trimodal therapy and the other chemotherapy, definitive radiation therapy, followed by more chemotherapy (J Clin Oncol 1995; 13(8): 1880-92, J Clin Oncol 2002; 20(16): 3454-60).

On the basis of those two trials, Dr. Albain and colleagues designed a study to compare the two strategies.

Patients with T1-3pN2M0 NSCLC received cisplatin-etoposide chemotherapy plus 45 Gy radiotherapy. In the absence of disease progression, patients were randomized to surgical resection or to continue radiotherapy to a maximum dose of 61 Gy, followed by additional chemotherapy.

The primary endpoint was overall survival.

The authors reported findings on 396 patients. The surgery group had a median overall survival of 23.6 months compared with 22.2 months in the nonsurgical group.

Five-year survival was 27% with surgery and 20% without, a nonsignificant difference. Among patients who had N0 status at thoracotomy, median overall survival was 34.4 months.

Surgical resection was associated with significant improvement in progression-free survival (12.8 months versus 10.5 months, P=0.017). Five-year PFS was 22% with surgery and 11% without.

The most common grade 3-4 toxicities associated with chemotherapy and radiation therapy were neutropenia and esophagitis, which occurred in 38% and 10% of the surgical group and 41% and 23% of the nonsurgical group, respectively.

The surgery group had an 8% treatment-related mortality, compared with 2% in the nonsurgery group. The mortality disparity led the authors to perform an unplanned, exploratory analysis of overall survival by type of surgical procedure.

Overall survival matching analysis was feasible for 90 of 98 lobectomies and 51 of 54 pneumonectomies. Median overall and five-year survival with lobectomy was 33.6 months and 36% versus 21.7 months and 18% without surgery (P=0.002).

Median overall survival did not differ significantly between groups in the comparison of pneumonectomy versus no surgery.

However, the trend was toward better survival without surgery: median overall survival of 29.4 months versus 18.9 months with pneumonectomy. Five-year survival was 22% with pneumonectomy and 24% without surgery.

The results provide "clear arguments in favor of surgery in well-selected subsets of patients," according to authors of an invited commentary.

"Can we undertake surgery in patients with stage IIIA(N2) NSCLC after induction chemoradiotherapy for now on? Yes, we can -- selectively in patients with less extensive resection . . . than pneumonectomy," Wilfried Eberhardt, MD, Georgios Stamatis, MD, and Martin Stuschke, MD, of University Hospital Essen in Germany, wrote.

"Further data from randomized trials are urgently needed to define the best selection criteria for bimodal or trimodal treatment," they added.

The authors and the editorialists declared no conflicts of interest.

Primary source: The Lancet

Source reference:

Albain KS, et al "Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small cell lung cancer: a phase III randomized controlled trial" Lancet 2009; DOI:10.1016/S0140-6736(09)60737-6.

Additional source: The Lancet

Source reference:

Eberhardt WEE, et al "Surgery in stage III non-small cell lung cancer" Lancet 2009; DOI:10.1016/S0140-6736(09)61026-6.

Additional Lung Cancer Coverage »

Link to comment
Share on other sites

Join the conversation

You can post now and register later. If you have an account, sign in now to post with your account.

Reply to this topic...

×   Pasted as rich text.   Restore formatting

  Only 75 emoji are allowed.

×   Your link has been automatically embedded.   Display as a link instead

×   Your previous content has been restored.   Clear editor

×   You cannot paste images directly. Upload or insert images from URL.

  • Create New...

Important Information

By using this site, you agree to our Terms of Use.