Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials Journal Article
| Authors: | Fleming, M. T.; Morris, M. J.; Heller, G.; Scher, H. I. |
| Article Title: | Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials |
| Abstract: | To the investigator and clinician, prostate-specific antigen (PSA) level is a seemingly perfect outcome measure because it is easily assessable, quantitative, reproducible, and inexpensive. Whether post-therapy decline in PSA reflects true clinical benefit, and whether post-therapy declines can be used as an intermediate endpoint for accelerated drug approval is still open to question. At present, no drug has been approved strictly on the basis of a post-treatment decline in PSA, as it is unproven that such PSA changes are surrogates for true clinical benefits. Post-therapy PSA changes have been associated with improved survival in patients with castrate metastatic disease. The role of PSA changes as potential surrogates of clinical benefit have only been explored to a limited degree because to date, only two prospective randomized trials showing a survival benefit have been reported. Such trials are necessary, but not a sufficient pre-requisite to explore the potential role of any outcome measure as an intermediate endpoint. The clear demonstration that a post-therapy PSA change can account for all of the treatment effects seen is not yet available. A cytotoxic drug that does not produce any PSA decline is unlikely to be effective, but the converse is not always true because not all PSA rises represent a treatment failure. It is important to recognize that there are a range of clinical benefits to patients that can improve the quality and possibly the duration of survival, independent of PSA. |
| Keywords: | cancer survival; treatment outcome; survival analysis; survival rate; treatment failure; overall survival; prednisone; clinical trial; disease course; review; bevacizumab; placebo; drug withdrawal; monotherapy; drug approval; bone metastasis; disease free survival; outcome assessment; cancer palliative therapy; reproducibility; prostate specific antigen; quality of life; computer assisted tomography; tumor volume; etoposide; granulocyte macrophage colony stimulating factor; cohort analysis; combination chemotherapy; hemoglobin; practice guideline; calcitriol; cancer mortality; docetaxel; prostate cancer; prostate-specific antigen; prostatic neoplasms; goserelin; leuprorelin; alkaline phosphatase; drug research; karnofsky performance status; quantitative analysis; echography; mitoxantrone; kallikrein; lactate dehydrogenase; metastasis potential; bicalutamide; flutamide; hydrocortisone; nilutamide; protein family; endpoint determination; testosterone; antigen presenting cell; clinical trials; suramin; bone scintiscanning; zoledronic acid; bone radiography; atrasentan; lexidronam samarium sm 153; strontium 89; estramustine; acid phosphatase prostate isoenzyme |
| Journal Title: | Nature Clinical Practice Oncology |
| Volume: | 3 |
| Issue: | 12 |
| ISSN: | 1743-4254 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2006-12-01 |
| Start Page: | 658 |
| End Page: | 667 |
| Language: | English |
| DOI: | 10.1038/ncponc0664 |
| PUBMED: | 17139317 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 21" - "Export Date: 4 June 2012" - "Source: Scopus" |
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