When Progressive Disease Does Not Mean Treatment Failure:

[D.ap]

"When Progressive Disease Does Not Mean Treatment Failure:
Reconsidering the Criteria for Progression"



"Progression Confirmation
Trial design in prostate cancer has historically relied upon PSA
measurement and bone scans for efficacy assessment; however,
these two metrics can be vulnerable to fluctuations that may not
represent actual changes in the tumor. To overcome the problem of
progression incorrectly being identified too early, the PCWG2 has
recommended that progression be confirmed with a repeat assessment
according to a standardized set of criteria (26). Because of the
variable course of prostate cancer, they discourage the consideration
of any changes before 12 weeks as an indication of treatment failure.
Confirmation of progression is mandated if new lesions are documented
on the first posttreatment scan, to control for the “flare”
phenomenon that can be observed in patients who are responding
but whose bone scans worsen because the bone is healing. The
PCWG2 criteria therefore serve as a semiquantitative indicator of
progression, control for pseudoprogression, and standardize the
termination of treatment for patients who are participating in the
study. Although the PCWG2 progression criteria may reduce the
number of patients who discontinue use of the study drug early,
the criteria are still undergoing clinical qualification in three prospective
randomized studies (28). Confirmation of progression was
also a component of the landmark trial by Zubrod et al. (1), which
was published in 1960; but this practice was not incorporated into
subsequent response criteria (Table 1). Separately, the bone scan
index, a more quantitative measure of bone scan burden, is under
development as a trial endpoint in prostate cancer (28). Changes
in bone scan index are more closely associated with survival than
changes in PSA in patients with castrate-resistant prostate cancer
although a bone scan index–based definition of progression has not"



https://www.ncbi.nlm.nih.gov/pmc/articl ... djs353.pdf

[Olga]

Awesome article, Debbie. We talked about it before, and our patients lost their places in the clinical trials due to the pseudo-progression. I would also like to see them working on the "bad players" dilemma - when most of the mets are responding and some single ones are not, or when there is a clear good response in some organs but not in the other ones (like we had the mets in the lungs regressing and subcutaneous soft tissue or bone progressing). IMHO it should not be a reason for discontinuation of the study drug as the patient is having a benefit and single mets could be treated locally - if allowed by the rules.