Projected tumor size and projected PSA uncover hidden drug activity

Now that surrogacy of static values of PSA and PSA-DT is being questioned for targeted therapies, new techniques of response evaluation are under study. One attempt to quanti-tate treatment efficacy redirects attention from PSA-DT to PSA-specific growth rate (PSA-SGR) [69, 70, 71]. Generally ignored, projected tumor and marker value play a particularly important role in uncovering and quantifying hidden, cytostatic or cytolentic drug effects. Projected tumor volume or marker value is calculated prior to the initiation of therapy and based on the specific growth rate constant (SGR) before the start of therapy. The projected value is illustrated in Figure 7. This growth projection captures the inherent tumor SGR before therapy and predicts what the outcome (projected tumor or marker volume/value) would be at any future date in the absence of treatment or tumor mutation. Older cytotoxic drugs, when effective, inhibit innate growth by programmed cell death and apoptosis resulting in autophagy and tumor cell lysis [60, 72]. This results in a measurable reduction of tumor size. Interestingly, these drugs are often in part cytostatic or cytolentic and depending on dose may result in stable disease. Keep in mind that prolongation of cytostatic or cytolen-tic suppression by any drug may eventually induce cytotoxicity and cell lysis [60] Figure 6.

Different combinations of static/lytic drug activity may result in reduced tumor/marker size or complete tumor growth inhibition without clinically detectable change in tumor size. Under these circumstances, use of projected growth uncovers hidden suppression of proliferation. A common clinical scenario occurs when during treatment, a tumor increases in size but much less than projected. Unless the clinician calculates what the projected tumor size should be, the true degree of tumor suppression is not appreciated Figure 7.

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