The cascade theory of metastatic spread: are there generalizing sites?

The term "cascade spread," with regard to metastases, is being used ambiguously. some workers take it to mean that cancers metastasize along preferred pathways, others infer that some sites are seeded first and that further metastases proceed from these sites rather than from the primary tumor. It is our opinion that the statistical arguments used to support the second approach have serious flaws. Given our present understanding of the metastatic process, a spread along preferred pathways is supported both by physiologic as well as statistical considerations. However, the contribution "generalizing sites" to the spread of metastases remains unproven.