Mediastinal Lymph Node Metastasis from Non-small-cell- bronchogenic carcinoma- Current Literature Review: <

F.W.Grannis Jr. MD

April 10, 1993

University of California, San Diego ;

Department of Surgery Grand Rounds

The most recent revision of Grateful Med allows improved computer search of mediastinal lymph node metastasis. A synopsis of recent articles follows. Of note are the minimal contributions in this area by American surgeons. Most of the data included is taken from abstracts rather than complete manuscripts because of my inability to translate the foreign language articles. Because of the incomplete nature of the data this review should not be construed as a meta-analysis. The similarity of results in the many series is, however, striking, suggesting that the results are reproducible and reasonably accurate.

1. Yusa- Local recurrence-18% stage I-9% Types lymphatic-15% stage II-15% margin- -2% stage III-35% effusion -2% endobronch 1% Conclusion: lymphatic recurrence is the most frequent pattern after curative resection of lung cancer. Incidence was reduced by post-operative radiation.

2. Funatsu - 100 pts with lung CA (76 adCA 24 sqCA) with positive mediastinoscopy Rx with thoracotomy.

   13 curative resection _28% 5 yr survival.

   83 non-curative res 0% " "

   sqCA 12% adCA 0% " "

   T1-T2 9% T3 0%.

3. Shibuya -

   Average weight of metastatic mediastinal lymph nodes= 2.34g

   normal " " = 0.83g.

4. Watanabe - NSCLCA- N2-199 cases- 144 cur. res 20.3% 5-yr surv. Worse survival in RN2 to superior mediastinum + LN2 to inferior mediastinum.

   Worse survival in single level subcarinal and multilevel mets.

   Conclusion: Extensive mediastinal dissection should be performed irrespective of the location of the primary tumor.

5. Ishida - 221 pts with T1 lung cancer.

   T1A <1.0 cm 8 pts- N0 100% N1-0% N2-0% 5yr- 80%

   T1B 1.0-2.0cm 84pts- N0 83% N1-5% N2-12% " -74%

   T1C 2.1-3.0cm 129pts- N0 62% N1-12% N2-25% " - 51%

   28.6% of N2+ "skipped" N1

   Conclusion: It is important to do mediastinal lymphadenectomy.

6. Fujisawa - Surgery + chemoRx of NSCLCA 5 yr survival- 37%

   Stage I- 59%

   Stage II- 33%

   Stage IIIA- 21%

   Stage IIIB- 12%

   Stage IIIA shows 20% local recurrence even with complete resection.

   Conclusion: Further improvement in surgical proceedure and adjuvant therapy is needed.

7. Watanabe - 124 pts with N2 NSCLCA with complete nodal dissection.

   1 level=47% ; 2 level=29%; 3 level=12%; 4 level=12%. RUL- +lower mediastinal nodes 33%.

   Also common LLs -+ upper med nodes

   Skip metastases were frequent.

   Conclusion: extensive mediastinal dissection should be recommended in surgery for lung cancer irrespective of the location of the primary tumor.

8. Maggi - 1103 pts NSCLCA- 824 complete resection

   N0=539 5 yr survival=60%

   N1=190 " " =46%

   N2=236 " " =23% N2=N1+N2

   36.2% "skip" mets

   Most frequent nodes+=

   • 1. R paratracheal
   • 2. L preaortic
   • 3. Subcarinal

   Poor prognosis if upper and lower mediastinal nodes +.

9. Naruke - 1654 pts NSCLCA compare survival with and without med lymph node dissection.

   426 pts with N2M0 25.8%

   345 c node dissection 5 yr survival T1N2=30%

   T2N2=14.5%

   T3N2=12.9%

   Overall 15.9% c no med node dissection 5 yr survival=6.7%.

   Conclusion: To improve end results, it is important to perform as many curative operations with mediastinal lymph node dissections as possible.

10. Weber - 1003 pts. "Radical lymph node dissection takes 30-60 minutes without increasing the survival time, only the rate of regional metastases is diminished. The fate of the patient is dependent on the spread of hematogenous micrometastases.....simple extirpation of regional lymph nodes as an en-bloc proceedure will be sufficient."

11. Yamaguchi - 723 pts c NSCLCA- "The recurrence rate of slightly advanced cases with complete mediastinal lymph node dissection was lower than those with incomplete dissection, indicating the importance of complete mediastinal node dissection for a strategy postoperative recurrence of primary lung cancer.

12. Korst - 345 pts with mediastinoscopy

    - sensitivity for + med nodes=50%

    N2+ 72 pts no resection 5 yr survival = 3.1%

    26 pts resection+mnd "

    Conclusion: Complete mediastinal node dissection should be performed at the time of resection to assure accurate staging.

13. Kris - Memorial NY- 73 pts with "clinically apparent" (i.e. seen on plain film CXR and therefore extensive +N2 disease)

    Rx with MVP preop.

    77% objective response 10%CR 67%PR

    79% explored 60% complete resection

    - c complete res 27 mo median survival

    15% disease free survival at 5 years (actual).

14. Burkes - Toronto General Hospital- 39 pts with +N2 disease

    "technically unresectable" treated preop with MVP.

    64% response- 8%-CR 56% PR-

    22/39 operated- 18 complete resections- 9% op mortality!! 2' BPF-

    29 mo median survival for complete res-40% 3 yr survival.

    Med suvival for whole group is 18 mo and 26% at three years.

    Conclusion: MVP appears to be an effective regimen the combined with surgery prolongs survival in N2 lung cancer. Treatment related complications are a serious problem.

    PERSONAL OBSERVATIONS: Stage IIIA lung cancer is a huge problem.

    There are approximately 30-40,000 cases in this stage discovered in the USA each year.

    Current management is proof of stage by mediastinoscopy, followed by radiation therapy +/- ChemoRx.

    In my practice this resulted in 5 years survival of 3%.

    Clearly a different approach is warranted.

    Mediastinal lymph node dissection in conjunction with pulmonary resection has the following benefits.

    • 1. Definitive staging is achieved. Patients who are inappropriately understaged, i.e. undiscovered N2 disease is left at surgery, are doomed.
    • 2. Patients will probably not be eligible for inclusion in prospective adjuvant therapy protocols unless such dissection is done.
    • 3. Mediastinal node dissection may result in a small improvement in survival in SELECTED patients with resectable mediastinal lymph node metastases.

      A standard technique of mediastinal lymph node dissection is required. Such a technique exists but has not been included in standard thoracic surgical texts. Nodal dissections would best be coded by including the numerical designations of mediastinal node areas by the Naruke classification e.g. mediastinal node dissection 2,4,7,8,9 (i.e. dissection includes upper and lower paratracheal , subcarinal, posterior mediastinal and inferior pulmonary ligament nodes).

      Complete mediastinal node dissection can be carried out in 30- 45 minutes by a simple, easily taught technique with minimal morbidity. In my personal series of over 100 cases mortality is 3%. Morbidity is 20%. Total chest tube drainage is increased and tubes have to be left in for an extra day on average.

      Patients with N2 disease must be carefully selected before advising surgical resection. Pre-operative CT scans will allow recognition of patients with "bulky" mediastinal node metastases that involve large nodes, multiple levels of metastasis, contralateral involvement and obliteration of normal tissue planes. Such cases will almost certainly not be completely resectable.

      Patients with such "bulky", "clinically apparent" or "technically unresectable" N2 disease may benefit from so called neo-adjuvant chemotherapy, but it must be recognized that morbidity and mortality of such chemotherapy is high especially in patients with obstructed bronchi. Furthermore, surgery is very difficult in these patients who have a fibrous obliteration of normal dissection planes. Operative mortality is very high 5-9% even when performed by very experienced surgeons.

      There is minimal information on what adjuvant therapy was given to patients in the above series treated with mediastinal node dissection. There would seem to be enough evidence for the efficacy of this approach to justify prospective studies with a surgery only group compared with post-op radiation and with post-op radiation therapy and chemotherapy.

      Because of the high pre-operative and post-operative morbidity and mortality associated with neo-adjuvant chemotherapy this approach should not be applied to patients with resectable disease outside of a clinical trial..

      REFERENCES:Mediastinal Lymph Node Dissection for Bronchogenic Carcinoma

      ---

      1. Yusa T, Momiki S, Fujino M, Sekine Y et al. [Study on local recurrence in patients undergoing curative resection of lung cancer] Nippon Kyobu Geka Gakkai Zasshi 1992;40:1973-7.
      2. Funatsu T, Matsubara Y, Yasuda Y, Kosaba S et al. [Surgical treatment of lung cancer with mediastinoscopic positive lymph nodes.] Nippon Kyobu Geka Gakkai Zasshi 1992;40:930-6.
      3. Shibuya K, Kimura H, Yamaguchi Y, Fujisawa T et al. [Comparative study of weight of regional lymph nodes in association with the presence of metastasis in primary lung cancer patients.] Nippon Kyobu Geka Gakkai Zasshi 1991;39:1747-51.
      4. Watanabe Y, Hayashi Y, Shimizu J, Oda M, Iwa T. Mediastinal nodal involvement and the prognosis of non-small cell lung cancer. Chest 1991;100:422- 8.
      5. Ishida T, YHano T, Maeda, Kaneko S et al. Strategy for lymphadenectomy in lung cancer three centimeters or less in diameter. Ann Thorac Surg 1990;50:708-13 and 691-2.
      6. Fujisawa T, Yamaguchi Y, Shiba M, Baba M et al. [Present status and problems of surgical treatment of non-small cell lung cancer.] Nippon Kyobu Shikkan Gakkai Zasshi 1990;28:210-5.
      7. Watanabe Y, Shimizu J, Tsubota M, Iwa T. Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. Chest 1990;97:1059-65.
      8. Maggi G, Casadio C, Mancuso M, Oviaro A et al. Resection and radical lymphadenctomy for lung cancer: prognostic significance of lymphatic metastases. Int Surg 1990;75:17-21.
      9. Naruke T, Goya T, Tsuchiya R, Suemasu K. The importance of surgery to non-small cell carcinoma of the lung with mediastinal lymph node metastasis. Ann Thorac Surg 1988;46:603-10.
      10. Weber J, Al-Zand K, Grabner D, Beyer D, Haupt R. [Regional metastasis of bronchial cancer and therapeutic consequences. A contribution to the problem of the prognostic effectiveness of lymphadenectomy.] Zentralbl Chir 1985;110:1242-52.
      11. Yamaguchi Y. [Strategy and treatment of postoperative recurrence of primary lung cancer]. Gan To Kaguka Ryoho 1983;10:2258-67.
      12. Korst RJ, Thayer J, Brown L. Cervical mediastinoscopy: routinely indicated in the community hospital setting? Abstract: Society of Surgical Oncology Annual Meeting, Los Angeles CA March 19, 1993.
      13. Kris MG, Martini N, Gralla RJ, Pisters KMW, Heelan RT. Primary chemotherapy in stage IIIA no-small cell lung cancer patients with clinically apparent mediastinal lymph node metastases: focus on five-year survivors. Lung Cancer 1993;9:369-376.
      14. Burkes RL, Ginsberg RJ, Shepherd FA, Blackstein ME, Goldberg ME, Waters PF, Patterson GA, Todd T, Pearson FG, Cooper JD, Jones D, Lockwood G. Induction chemotherapy with MVP (mitomycin-C + vincesine + cisplatin) for stage III (T1- 3, N2, M0) unresectable non-small cell lung cancer: the Toronto experience. Lung Cancer 1993;9:377-82.