When should a CLL patient have a CT scan?
The first thing to say is that for the past 30 years the staging of CLL has been carried out very satisfactorily without CT scans. Indeed all the predictive information that is based on Rai or Binet staging specifically excludes CT scanning. However, it stands to reason that some Rai stage 0 patients will in fact have enlarged retroperitoneal lymph nodes (this means nodes at the back of the tummy)undetectable by clinical examination, and these patients will have the prognosis of stage I patients rather than stage 0 patients, and that in some patients the glands will be of sufficient size as to justify immediate treatment.
If CT scanning is used to stage patients, then patients who are truly stage 0 will have a better prognosis than historical data shows, but we are in the dark about what happens to patients whose only evidence of enlarged lymph nodes is what is detectable by CT scanning.
A new paper from Professor Montserrat's group is about to be published in J C lin Oncol which helps to resolve this.
The Barcelona group did abdominal CT scan on 140 stage 0 patients. 27% had an abnormal CT scan. This correlated with increased bone marrow infiltration, high lymphocyte count, high ZAP-70 expression and short lymphocyte doubling time. Patients with an abnormal CT scan had a shorter time to first treatment than those with normal CT scans (median 3.5 years compared with median not yet reached). In a multivariate analysis only abnormal CT scan and high ZAP-70 correlated with disease progression. (Remember that the Barcelona ZAP-70 is one we believe in - it was published in NEJM under Crespo et al. It correlates very closely with unmutated VH genes).
In the light of this finding the International Working Group in CLL are minded to add to their advice on the management of CLL.
CT scans generally are not required for the initial evaluation, staging, or follow up. A recent study has found that patients in Rai stage 0 but with detectable abdominal disease by CT scans may have a more aggressive disease. Therefore, clinical studies evaluating the use of CT scans in CLL are strongly encouraged.
The IWCLL group are very conservative about changing recommendations, but I certainly think that there are situations where a CT scan would be indicated in the initial evaluation of patients in clinical practice.
Patients who are apparently stage 0 but have a lymphocyte count greater than 50,000 (possibly those greater than 30,000), overweight patients who are difficult to examine for lymph nodes, patients with 'B' symptoms, patients with lymphocyte doubling times of less than a year, patients with unmutated VH genes (or a reliable positive ZAP-70).
I know that some people who are worried by the radiation dose from a CT scan. This worry has been reinforced by an MRI specialist who has been writing on Medscape. I have to say that this is very much a lone view among medical imagers. Most, while recognizing that CT scanning does involve a large dose of radiation compared to that received from a chest X-ray, nevertheless agree that the risk of inducing a second cancer is very small compared to the risk of missing the correct diagnosis.
What about using ultrasound or MRI to diagnose retroperitoneal lymph nodes?
In some countries, the use of abdominal ultrasound is popular to assess the extent of lymphadenopathy and organomegaly in CLL. While it may be used in the clinical management of individual patients, this methodology is strongly investigator-dependent and should therefore not be used for the response evaluation in clinical trials. - so say IWCLL and I agree with them. Measurement of nodes on successive ultrasound scans is nigh on impossible, because you cannot really produce comparable views.
Similarly, the IWCLL view of MRI is this - "nuclear magnetic resonance imaging and other imaging techniques are generally not useful in the management of CLL." Again I agree, the view of lymph nodes is not precise enough.
While we are on the subject of imaging, the IWCLL say, "Positron emission tomography (PET) scans do not provide information that is useful in the management of CLL. PET scans, however, might become useful in the diagnostic evaluation and follow up of known or suspected Richter's transformation."
In clinical trials, the latest German trials demonstrate that the use of CT scans to evaluate how good a response is, is very worthwhile. Apparent complete remissions are nothing of the sort in many cases when CT scans are used to evaluate them. The IWCLL recommend, "In clinical trials where the treatment intent is to maximize complete remissions, neck, chest, abdominal and pelvic CT scans are recommended to evaluate the response to therapy. CT scans should be performed prior to the start of therapy and at the first restaging following therapy if previously abnormal".
Like all imaging examinations the doctor must first ask himselftheh question, "Why am I doing this?" and then answer the question, "How will it alter my management if I have this information?" If the answer to the first is, "Idon't know or because it is in the protocol" or the answer to the second is "Not at all or I don't know," then the CT scan should not be done.