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Beyond Stage & Tumor Size: More Pathology Variables Associated with Risk of Recurrence after Surgery

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The decision about pursuing post-operative treatment is often difficult and requires carefully weighing the risks of treatment with potentially challenging and even dangerous chemotherapy against the potential to eradicate micrometastases and actually lead some people to be cured who otherwise wouldn’t be. It’s important to remember that some people are already cured, while others won’t be cured even with treatment. We’re pursuing treatment for the 5-15% higher survival rate at 5 years from adding chemo, presumably representing the proportion of people who have micrometastatic cancer cells that are apparently eradicated by getting 3-4 cycles of platinum-based chemotherapy:

Scagliotti adjuvant chemo explanation

(Click image to enlarge)

The general guidelines we use to assess risk for recurrence include stage of the cancer as the primary focus. I also described the relevance of tumor size as an important factor to stratify risk of recurrence in my recent post on that topic. But there are other potentially relevant factors for people who have cancers that are “on the bubble” about whether they have enough risk to justify the side effects and some real risks of post-operative chemotherapy.

I’ve covered the topic of tumor grade being predictive of recurrence risk in a prior post. In addition to stage, primary tumor size, and cancer grade, there is the factor of tumor histology subtype (squamous vs. adenocarcinoma). Presumably because of its greater tendency to be associated with micrometastases and spread early, patients with stage I adenocarcinomas (stages IA and IB) have been shown to have a higher risk of recurrence than those with squamous cancers (abstract here):

Early stage NSCLC survival by histology

Remember also that patients with stage I adenocarcinomas also have a higher risk of being “upstaged” by finding unexpected cancer involvement in the mediastinal (mid-chest) lymph nodes, as I described in a prior post. This is the same theme, that squamous cell carcinomas tend to remain localized longer than adenocarcinomas. On the other hand, BAC tumors have a different behavior than invasive adenocarcinomas and tend to be associated with a more favorable survival (described in prior post)(abstract here):

Breathnach stage I BAC survival

Finally, there is also the minority of patients large cell neuroendocrine carcinomas, who appear to have a less favorable prognosis than other NSCLC subtypes (described in a prior post).

Finally, another factor to consider is the involvement of the visceral pleura, the lining on the outside of the lung. This is reflected in the staging system, since even a smaller tumor that measures less than 3 cm becomes a stage IB NSCLC if it involves the visceral pleura. Here’s a survival curve from a series of stage I cancers that shows the difference in survival between those patients who had or did not have visceral pleural invasion (sometimes abbreviated VPI)(abstract here):

VPI Stage I survival

So that’s a lot of factors from the pathologic report, all worth considering when weighing the pros and cons of chemotherapy after surgery in more boderline cases. And we haven’t gotten to imaging factors yet. That’s the next topic…


4 Responses to Beyond Stage & Tumor Size: More Pathology Variables Associated with Risk of Recurrence after Surgery

  • topper says:

    Dr.West,
    As I understand it under the new system of staging a tumor larger than 4cm will be
    listed as a T3.Is there an upper limit on the T3 classification? I believe the N classification system stays the same. How does the change say from a T2 to a T3 affect
    The prognosis? I realy appreciate your
    answering our questions and encouragment.
    Topper

  • Dr West
    Dr. West says:

    Actually, the new staging system proposes that T1 tumors are up to 3 cm, and that T2 tumors are >3 up to 7 cm, divided between T2a (>3 to 5 cm) and T2b (>5 to 7 cm). Beyond 7cm, they’d be classified as at least T3. Prognosis in early stage also depends on N stage, so that T2aN0 is more favorable than with N1, which has essentially the same prognosis (and overall stage, IIA) as T2b N0. But then T2b N1 is stage IIB, with a slightly worse prognosis, the same as T3 N0, while T3 with N1 or N2 nodes involved is stage IIIA (and worse prognosis).

    It’s still confusing. The ink is still wet on this staging system, and we’re all jst becoming familiar with it.

    -Dr. West

  • topper says:

    Dr.West,
    Thank you for your answer to my questions
    submited on October 4th at 7:05pm.I was staged 111a. Tumor in upper right lobe measured 7.7cmx7.7cm. Had right pneumonectomy in June,2004. All scans since have been clear.Lymph node labeled 4R was cancerous.
    Does involvment of this particular lymph node
    carry a worse prognosis than say the involvment of other nodes in the mediastinal
    area? Am i right in saying that the cancer cells are probaly still in my body but my body’s immune system has prevented a recurrence. Thanks ,Dr. West for your help.

  • Dr West
    Dr. West says:

    I would say that a 4R node wouldn’t lead me to believe it is worse than another mediastinal node — it would clearly be worse to have a node on the other side of the mediastinum, which would make it N3, or likely if it went from the right upper lobe all the way down to the the subcarinal region, which is where you’d expect lower lobe cancer to drain to. Having cancer travel further from the point of origin tends to have a worse prognosis.

    Otherwise, there is relevance in whether involved nodes were actually enlarged, such as more than 1 cm on CT, or have just microscopic involvement in a normal-sized lymph node. The most favorable situation with mediastinal nodal involvement is a single microscopically involved lymph node, not enlarged. Those patients tend to have a much lower recurrence rate than patients who have either enlarged mediastinal nodes on scans or multiple lymph node “stations” (areas of the mediastinum) involved.

    I wouldn’t say that there are likely cancer cells still in the body. it’s possible that all of the cancer cells were removed at surgery, or that there are micrometastatic cells that may be held in check by the immune system (we really don’t know much about this concept, and it’s just speculation), or that there are micrometastatic cells that can grow later into visible metastatic lesions later.

    We often give chemotherapy, and sometimes radiation as well, after surgery for stage IIIA, N2 NSCLC, given the risk for residual viable micrometastatic disease. There is also evidence that giving chemo, at least, after surgery for stage IIIA disease can reduce the recurrence rate, at least modestly.

    -Dr. West

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