CHAPTER 18: STAGE 2 NON-SMALL CELL CANCER
18.1 TREATMENT OVERVIEW
Stage 2 comprises a diverse group:
“Patients with stage II NSCLC represent a heterogeneous group, since stage II consists of patients with T1-2N1 or T3N0 tumors. By definition, patients with tumors invading the chest wall apex, mediastinum, diaphragm, or even the mainstem bronchus may all have T3 tumors. The extent of the data available regarding treatment of each of these different groups is therefore limited.” Scott (8).
18.11 Surgery as the Preferred Option
Surgery is the treatment of choice for stage II patients. As with stage 1, careful consideration of pulmonary reserve is required for major surgery. Mortality rates tend to be age related, and in the 3%-5% area. A 78 year former smoker with pulmonary abnormalities is more likely to suffer an adverse result than a 50 year old in otherwise good health.
Stage II patients who are not recommended for surgery may undergo radiation with curative intent. (NCI 6). Among patients with excellent performance status, a 20% 3-year survival rate may be expected with a completed course of radiation. In one study, an overall 5 year survival rate of 10% was reported, but patients with small T1 tumors had a substantially higher rate.
18.13 Survival Rates
A 1999 article in the journal Lung Cancer states,
“For the 98 patients with postoperative lobar or hilar node metastasises, overall survival rates at 3 and 5 years of 45.2 and 37.3% were found. Fifteen (15.3% showed a local failure within the radiation field as a first failure relapse. Distant metastasises as first failure were noted in 38 patients (39%) with 12/38 brain metastasises.... At 5 years, a local progression free survival rate of 79% and a distant metastasis free survival rate of 52% was noted.” Rodrigues (5).
Another found survival rates as follows: 1 year 70%, 3 year 50%, 5 year, 30%.
18.131 Survival Rate Differences Between Adenocarcinoma and Squamous Cell
Some studies have reported differences in survival rate for stage 2 based on type:
“For the 71 stage II patients with a squamous histology, a 5-year survival rate of 44% was noted as opposed to 14% for patients with a large cell or adenocarcinoma. Although the local failure was not different (the term local failure meaning reappearance of the tumor in the area of radiation or where the tumor was removed) 17% for squamous, 11% for non-squamous, the non-squamous group failed more often at distant sites. From the 27 patients, 18 developed metastasises as a first failure with 8/27 (30%) brain metastasises. For the squamous group, 20/71 (28%) developed distant metastasises, with 5/71 brain (metastasises).” Rodrigues, (5).
18.21 An Uncertain Area
Recall that stage 2 means that the tumor has penetrating adjoining lymph nodes. Thus the potential for dissemination of the cancer is greater and the chance that surgery can remove the entire tumor less. Combining surgery with some type of post-surgical treatment for eradicating any remaining tumor cells makes logical sense. However, precisely what should be done and what benefits can be realized continues to be debated.
With lymph node involvement at stage 2, the possibility of recurrence or metastasis increases. One may reason that in addition to radiating the area of the tumor to kill any cancer cells missed at surgery, why not add chemotherapy to attack any cells in that or other areas? While the approach carries with it some logic, clinical studies have not shown success, and many physicians reason that patients should not be required to deal with chemotherapy treatment until definitive benefits are not shown. Here are results from one study.
A presentation at the 2000 World Conference on Lung Cancer summarizes the results: “This large, well-conducted, multicenter study suggests no clinical advantage at all for adding chemotherapy to radiation therapy in the management of resectable lung cancer. While newer chemotherapy agents are available, it is not clear that these drugs would change the fundamental outcome compared with the widely used platinum-based regimen used in this study. It is fair to say that the use of chemotherapy in the adjuvant setting of stage 2 or 3A NSCLC remains investigational.” Burstein(1) , see also (2)(3).
Others have reached different conclusions, “Chemotherapy used alone or in combination with radiation therapy postoperatively resulted in prolonged time to disease progression and a modest improvement in survival. However, long-term survival was not affected. The precise role of adjuvant chemotherapy and/or radiation therapy in patients with stage II NSCLC remains to be determined. Investigators are also exploring the use of preoperative and postoperative paclitaxel and carboplatin chemotherapy in patients with stages Ib, IIa, IIb, and IIIa NSCLC.” (4) (U.S. Pharmacist).
18.3 GENE THERAPY FOR STAGE 2
18.31 Rationale for Stage 2 Gene Therapy
Gene therapy probably makes the most sense at this stage, but interestingly has been tested the least. With stage 4 disseminated cancer, the possibility of reworking cell-signaling is limited, and at stage 1, why apply therapy to patients who likely have been cured. At stage 2, we have patients with relatively early disease, but the existence of lymph node involvement means that the possibility of cure with surgery is less than 50%. Unfortunately, there have been relatively few trials directed at stage 2 patients.
18.32 Epidermal Growth Factor Receptor Therapy
We discuss Iressa in our chapter on epidermal growth factor inhibitors. Patients with adenocarcinoma, BAC, non-smokers and light smokers are more likely to have lung tumors involving damage to the tyrosine kinase portion of the EGFR. Since Iressa which is a tyrosine kinase inhibitor, it is highly effective with this group. Tests have been developed to identify tyrosine kinase damage, and patients may wish to take it to assess treatment options.
1. Adjuvant Chemotherapy for Lung Cancer: Still No Benefit, World Conference on Lung Cancer (2000), www.medscape.com.
2. Non-Small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. BMJ. 1995;311:899-909.
3. Burstein, SM, Adak S, Wagner H, et al. A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer. N Engl J Med. 2000;343:1217-1222.
4. www.uspharmacist.com current Treatment of Non-Small Cell Lung Cancer, (US Pharmacist Continuing Education).
5. Rodrigues, The Impact of Surgical Adjuvant Thoracic Radiation for different Stages of Non Small Cell Lung Cancer: the Experience from a Single Institution, Lung Cancer 23 (1999) 11-17.
7. Riantawan , Survival analysis of Thai patients with non-small-cell lung cancer undergoing surgical resection, J Med Assoc Thai. 1999 Jun;82(6): 552-7.
8. Scott, Treatment of Stage II Non-small Cell Lung Cancer , Chest. 2003;123:188S-201S.
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