SURGERY SECTION - CENTIMETER LUNG CANCER: PREVALENCE OF NODAL DISEASE AND IMPLICATION FOR SURGICAL THERAPY by Daniel Miller, MD

SLIDES & TRANSCRIPTS
Tuesday, June 19

SURGERY SECTION - CENTIMETER LUNG CANCER: PREVALENCE OF NODAL DISEASE AND IMPLICATION FOR SURGICAL THERAPY

Daniel Miller, MD

Slide 1: Introduction

DR. MILLER: Thank you. I just want to recognize the other members within our division of general thoracic surgery who helped in this review, and in the cases over the years, Claude Deschamp, Frank Nichols, Mark Allen, and Peter Paralero. Just real quick to put things in perspective, as you know, the majority of patients who present with a lung cancer have advanced disease.

Slide 2: Introduction

Here is a patient with a large lesion in the left upper lobe. Jim Jett would say that's nothing can be done for that, but a little pretreatment. We did take care of that somehow.
But what we are going to focus on today is this lesion here. The question is, what should we do for that?

Slide 3: Introduction

In regards to the controversy today over 1 centimeter or less lung cancers, what type of resection should be done, a lobectomy or a limited resection such a segmentectomy or a wedge? What type of approach should be carried out? Thoracotomy or thoracoscopy? Should there be a complete lymph node dissection or a sampling? Hopefully, that will be answered from the American College of Surgeons Oncology Study of the Z30 trial. Also, is there any role for any other type of treatment, either neoadjuvant, adjuvant, chemoprevention? That will be answered in the future.

Slide 4: Methods

So to get a handle on our experience with 1 centimeter lung cancers at Mayo, we went back over a 20 year period and retrospectively looked at all of our T1 lung cancers, non-small cell lung cancers. There were 1,417 patients. This excluded neuroendocrine tumors, and also carcinoid tumors. We found 100 patients who had tumors that 1 centimeter or less in diameter, and this represented 7% of that population. And so the 100 patients is what forms the basis of our study today.

Slide 5: Demographics

In looking at these 100 patients, 56 were men and 44 were women. The median age was 67 years, with a range of 43 to 84.

Slide 6: Method of Detection

If you look in regards to the method of detection, 19 patients had diagnostic studies for symptoms. Fourteen of these had chest x-rays performed for fever, cough, or shortness of breath, while 5 of them had their malignancies found upon bronchoscopy because of hemoptysis; 81 of these patients had no symptoms at all, and they were found to have their lesions on incident radiologic assessment; 68 of those were by chest x-ray, and 13 by CT scan. Three of these patients were in our lung cancer screening study.

Slide 7: Tumor Location

. In regards to the tumor location, 89 of these lesions were out in the periphery, 3 were central lesions, and 8 had an endobronchial component.

Slide 8: Lung Resections

The type of lung resections that were performed, 75 patients had a formal resection, 4 of those were actually a bi-lobectomy, 71 were a lobectomy, and 25 had a limited resection, 12 of those being a segmentectomy, and 13 wedge excision.

Slide 9: Reasons for Limited Resections

The reasons for the limited resections; out of 25 patients, 12 of these were for poor pulmonary reserve, 6 for associated co-morbidities, 3 from prior lung resections - none of these were secondary to lung cancer - 2 of these were performed at the time of bypass surgery, and two of them had change in pathology or incidental finding on final pathologic examination.

Slide 10: Pathology

In regards to the pathological findings, 48% of these patients were adenocarcinoma, a little bit more than one-fourth were squamous cell cancers, 19% were bronchoalveolar , 4 were large cell, and 3 were undifferentiated.

Slide 11: Tumor Diameter

In regards to tumor diameter, 57 patients had tumors that were 1 centimeter in size, and only 5 patients had tumors that were less than 5 millimeter in size.

Slide 12: Lymph Node Evaluation

In regards to the lymph node evaluation, 9 patients had a preoperative mediastinoscopy, 5 of those were for lymph nodes greater than 1.5 centimeters in size, the other 4 were for medical co-morbidities. All of these were negative. Ninety-four of these patients had a complete mediastinal lymphectomy at the time of surgery, and 7 patients already had positive metastasis; 5 patients had hilar involvement, and 2 patients had N2 disease.

Slide 13: Surgical Stage

So therefore, in regards to surgical states, 93% of the patients had stage I disease, the majority of these were stage IA, and only patient had visceral pleural involvement. Stage IIA was 5%, and 2 patients with stage IIIA.

Slide 14: Operative Mortality

In regards to operative mortality, there were five post-operative deaths, 3 within the lobectomy group, and 1 within the limited group that died after discharge, but died at home on the post-operative 18th day from an aspiration pneumonia.

Slide 15: Reults of Follow-Up

Follow-up was complete in all 96 patients who survived the operation, and were discharged home. The time interval was between 4 and 214 months, and the median was 43 months.

Slide 16: Causes of Death

Cause of death in the 35 patients who died during the follow-up period, 12 patients died of lung cancer; 9 patients died of other malignancies; 6 for medical reasons; 4 from unknown; and 4 from the post-operative.

Slide 17: Overall Survival Statistics

If you look at overall survival for all of the 100 patients from all causes of death, it was 64% at 5 years.

Slide 18: Lung Cancer Survival Statistics

However, if you look at lung cancer survival and cause of death only, the 5 year survival was 85%.

Slide 19: Statistics for Overall Survival by Stage

If you look at the overall survival with regards to stage, stage I disease was 66%, and 43% for stage II and stage III. This is was not statistically significant because of the small number of stage II and stage III patients.

Slide 20: Statistics for Lung Cancer Survival by Stage

However, if you look at lung cancer survival, this was nearly significant at 0.07. The stage I survival at 5 years was 87%, compared to 64% for stage II and stage III.

Slide 21: Overall Survival - Lobectomy vs Limited Resection

In regards to resection, if you compare between lobectomy and limited resection, looking at overall survival, lobectomy at 5 years was 71%, and for limited was 33%. This was statistically significant.

Slide 22: Overall Survival - Type of Procedure

If you divided this out further to see what was the reason for that low death rate in the wedge resection, if you divide it out and the type of procedure, 71% lobectomy at 5 years, segmentectomy is 57%, and wedge excision alone was 27%. This was statistically significant.

Slide 23: Lung Cancer Survival - Lobectomy vs Limited Resection

If you look at lung cancer survival, lobectomy alone accounted for a 92% 5 year survival, whereas for a limited resection, it was 47%. This, however, was not statistically significant, because of the small number of limited patients.

Slide 24: Lung Cancer Survival - Type of Procedure

If you would divide these out further in regards to type of procedure, again 92% who had lobectomy, 75% for segmentectomy, and only 47% for wedge excision.

Slide 25: Overall Recurrence Rates

Eighteen patients developed recurrence during this time period; 10% had local disease; 6% had both; and 2% had distant disease.

Slide 26: Recurrence - Lobectomy vs Limited Resection

Recurrence, comparing lobectomy versus limited; in limited 28% of the patients developed recurrence in this group, whereas only 15% in the lobectomy group, however, this was not statistically significant.

Slide 27: Recurrence - Type of Procedure

However, if you would divide this out further between the wedge, segmentectomy, and lobectomy, 38% of the wedges had a recurrence, and this was statistically significant. It was interesting that the segmentectomy and lobectomy were similar.

Slide 28: Patient Parameters

To see if there was a difference in regards to preoperative patient parameters, if you look at gender, percent male, age, co-morbidities, how the lesion was detected, and tobacco use, there was no difference. The only significantly significant different between the patient populations of lobectomy and limited was the 49% FEV-1 versus the 68%, which was probably the reason for the limited resection.

Slide 29: Perioperative Perameters

If you look in regards to perioperative parameters, there was no difference in the groups between tumor grade, hospital stay, operative mortality, or complications.

Slide 30: Factors Not Affecting Survival

Factors not affecting survival on analysis was gender, method of detection, smoking status, preoperative FEV-1, co-morbidities, tumor histology, or tumor location.

Slide 31: Factors Affecting Survival - Univariate Analysis

Factors that did affect survival in univariate analysis, age greater than 65, tumor grade 3 or 4, nodal disease 1 or 2, and limited resection.

Slide 32: Factors Affecting Survival - Multivariate Analysis

However, in a multivariate analysis only two factors affected survival, age greater than 65, and tumor grade 3 or 4. And this was probably because of a small number in the limited group.

Slide 33: Conclusions

So in conclusion, we found that lymph node metastasis occurred in 7% of non-small cell lung cancers less than 1 centimeter in diameter. We feel that limited resection, especially wedge excision adversely affects overall and lung cancer survival for these small lesions. Also recurrence after limited resection, especially wedge excision is more common than after lobectomy, and this was statistically significant.

Slide 34: Conclusions

We feel that anatomical resection, either lobectomy or segmentectomy, should be performed. At the present time we would favor lobectomy if possible, to improve survival and decrease recurrence for these small tumors. Also, until the Z30 trial is completed, we feel that a complete mediastinum dissection is recommended in all patients. As you well know, the incidence for these small lesions will continue to increase as CT screening increases in the future.

Slide 35: Conclusions Future Studies

I'm just going to have one slide about possible future studies in regards to a surgical standpoint. I think one potential perspective study would be to compare lobectomy versus limited resection. And I would feel that hopefully, the question has been answered in regards to wedge excision for patients who can tolerate either.
I think lobectomy versus segmentectomy would be a possibility. And also from a radiologic standpoint, which could be a feeder into this, would be about PET scanning in these patients to determine the presence of metastatic disease outside the chest, as well as the need for complete lymph node dissection. And hopefully, we'll hear in the next talk about sentinel lymph nodes, and whether that is necessary.