Reply to Jiwnani et al.

Abstract

We thank Jiwnani et al. [1] for their interest in and comments regarding our recently published paper, outlining a new nodal classification based on the number of metastatic lymph nodes (LNs) or the ratio of metastatic to examined LNs (LNR) [2]. As we realized that the concerns raised by Jiwnani et al. are the main issues in our article, we specifically addressed these concerns in the discussion of our original article. We will discuss these issues one by one in more detail. With regard to the unreliability of new nodal classifications, as Jiwnani et al. correctly note, the number of metastatic LNs and LNR are influenced by the method of LN removal and the diligence of the pathologist examining the specimen. Therefore, a standardized method in nodal dissection and the pathological process should be established for a new nodal classification. This includes the minimum number of LNs to remove, as in the current nodal classification for stomach, colorectal and breast cancer. Regarding LNR, many surgeons may feel that LNR is less reliable than the number of metastatic LNs, because the ratio can widely vary if only a small number of LNs are examined. For example, one metastatic LN out of one examined LN is 100%, but one out of two is 50%. Therefore, we again emphasize establishing a standardized method of LN sampling. However, when established, LNR can be superior to the number of examined LNs because LNR includes an implication of the number of the examined LNs, which has been demonstrated to be a prognostic factor [3, 4]. Concerning the fragmentation of removed LNs, we think that this may be a specific characteristic of lung cancer operations. To resolve this matter, Wei et al. [5] proposed putting the fragments from one single LN into the same bottle and treating it as one LN. In addition, as outlined in our original discussion, the nodal classification based on LNR may be more stable than the nodal classification based on the number of metastatic LNs. This is because both the numerator and denominator of the calculation formula of LNR will increase at an equal rate, if fragmentation occurs in metastatic and non-metastatic LNs. Regarding clinical staging, we advocate that our proposed nodal staging system should be used in a postoperative setting to select more effective adjuvant treatment candidates. Therefore, we suggest that clinical and pathological staging be conducted separately as the TNM classification for breast cancer. Even if new nodal staging increases complexity, if a new nodal staging system can provide a better indicator to classify patients according to their probability of recurrence, adjuvant therapy can be more efficiently applied to more appropriate patients, and be associated with the improvement of survival. In this situation, we believe that the new nodal staging system will be supported and followed by most physicians and pathologists. Even though there are several issues still to be resolved, the numbers of metastatic LNs and LNR are more effective prognostic indicators than the current nodal classification.