Time factor and treatment strategies in subclinical disease

Rational biological development of treatment strategies for subclinical metastases has lagged behind such efforts with primary cancers: most adjuvant therapies for subclinical disease have been developed empirically, based on clinical observation. This paper reviews recent studies that point to rapid growth of subclinical disease. The effect of rapid growth of occult metastases and undetectable extensions of primary cancer is to increase the radiation dose necessary for their elimination if treatment duration is extended. This increase may be evident even when changes are made to short courses of treatment, consistent with no lag time between the start of treatment and rapid growth or regrowth of subclinical tumour deposits. This provides a strong rationale for avoiding gaps or delays in adjuvant treatments and suggest that accelerated regimens of radiation or chemoradiation may be advantageous in the treatment of subclinical disease provided that the total dose can be maintained or not greatly reduced from those used conventionally. Conversely, an escalation of total dose with a concomitant increase in overall treatment duration may not result in improved control rates because the rapid growth of small clonogen deposits might counterbalance the effect of the higher dose.