Challenging the Mantra of Randomized Controlled Trials to Answer Every Clinical Question

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COMMENTARY
Challenging the Mantra of Randomized Controlled Trials to Answer Every Clinical Question

Maurie Markman, MD
Disclosures | May 02, 2016

Hello. I'm Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia.

I wanted to briefly comment on a very interesting paper that appeared in the Journal of Clinical Oncology and also to challenge, in a very direct way, one of the conclusions of the investigators. The paper is entitled "Role of Adjuvant Therapy in a Population-Based Cohort of Patients With Early-Stage Small-Cell Lung Cancer."[1]

Obviously, all oncologists are aware of the devastating impact of small cell lung cancer. The vast majority of patients, of course, present with advanced-stage disease. Chemotherapy certainly results in objective responses in a substantial number of patients, but the overall outcome today in small cell lung cancer is far from adequate.

In a setting where a patient is operated on who appears to have early-stage disease and the surgeons are able to leave the patient without evidence of disease that can be seen, the question that comes up is, is there a role for adjuvant therapy? It's an uncommon situation, so it is obviously difficult to do randomized controlled trials. This is also a provocative issue that has been on the minds of many oncologists for a long time.

The authors of this paper used data from the National Cancer Data Base and specifically looked at the issue of R0 resections. From 2003 to 2011, 1574 patients were identified and were classified as having received adjuvant therapy or not. The group of patients who received adjuvant chemotherapy had a median overall survival of 66 months versus 42 months for patients who had not received adjuvant chemotherapy, with a 5-year overall survival of 53% versus 40% (P < .01).

These are extremely important data and are quite relevant for physicians caring for individuals with small cell lung cancer in this clinical setting. What I want to comment on specifically was the final point of this otherwise excellent paper, whereby the authors concluded that these findings should be evaluated further in randomized controlled trials.

Do we really need a phase 3 randomized controlled trial to address this question? Is this necessary for every study where we see such overwhelming population-based data? It is hard to do these trials with this kind of an outcome. This is a chemotherapy-sensitive disease and these data show a positive outcome, so is it really necessary to conclude at the end of a paper that randomized controlled trials are necessary?

we need to begin to challenge this mantra of randomized controlled trials as the answer for every question.


Is such a conclusion put in a paper because the authors can only get it published in oncology journals if they put in this kind of statement? I think we need to begin to challenge this mantra of randomized controlled trials as the answer for every question. This is a very important issue, as the population-based data are impressive and are published in the peer-reviewed literature. I would submit that we should now consider this to be a standard-of-care option in the management of patients with early-stage small cell lung cancer.

Thank you for your attention.