The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer-T, N, or M?

Gunar K. Zagars, Vivek S. Kavadi, Alan Pollack, Andrew C. von Eschenbach, M. Elizabeth Sands

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. Methods and Materials: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. Results: Serum PSA level became undetectable in 277 of the 280 (99%) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values ≤ 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between ≤ 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12%). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7% and a median of 5% to the pretreatment serum value. Because such back-extrapolated values estimate the potentially maximal micrometastatic contribution, metastatic disease at diagnosis contributes little to pretreatment serum PSA. Conclusion: In patients with clinically localized prostate cancer, putative micrometastatic disease contributes negligibly to the pretreatment serum PSA level even when the latter is high. Most likely such patients, when they have metastases, have a very low metastatic burden.

Original languageEnglish
Pages (from-to)21-32
Number of pages12
JournalInternational journal of radiation oncology, biology, physics
Volume32
Issue number1
DOIs
StatePublished - Apr 30 1995
Externally publishedYes

Fingerprint

antigens
Prostate-Specific Antigen
pretreatment
serums
Prostatic Neoplasms
cancer
Serum
metastasis
Neoplasm Metastasis
tumors
Prostatectomy
radiation therapy
Radiotherapy
Neoplasms

Keywords

  • Prostate cancer
  • Prostate-specific antigen
  • Radiation therapy
  • Radical prostatectomy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation

Cite this

The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer-T, N, or M? / Zagars, Gunar K.; Kavadi, Vivek S.; Pollack, Alan; von Eschenbach, Andrew C.; Sands, M. Elizabeth.

In: International journal of radiation oncology, biology, physics, Vol. 32, No. 1, 30.04.1995, p. 21-32.

Research output: Contribution to journalArticle

Zagars, Gunar K. ; Kavadi, Vivek S. ; Pollack, Alan ; von Eschenbach, Andrew C. ; Sands, M. Elizabeth. / The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer-T, N, or M?. In: International journal of radiation oncology, biology, physics. 1995 ; Vol. 32, No. 1. pp. 21-32.
@article{e639b184673b4ad781dea3bd65322adf,
title = "The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer-T, N, or M?",
abstract = "Purpose: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. Methods and Materials: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. Results: Serum PSA level became undetectable in 277 of the 280 (99{\%}) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values ≤ 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between ≤ 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12{\%}). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7{\%} and a median of 5{\%} to the pretreatment serum value. Because such back-extrapolated values estimate the potentially maximal micrometastatic contribution, metastatic disease at diagnosis contributes little to pretreatment serum PSA. Conclusion: In patients with clinically localized prostate cancer, putative micrometastatic disease contributes negligibly to the pretreatment serum PSA level even when the latter is high. Most likely such patients, when they have metastases, have a very low metastatic burden.",
keywords = "Prostate cancer, Prostate-specific antigen, Radiation therapy, Radical prostatectomy",
author = "Zagars, {Gunar K.} and Kavadi, {Vivek S.} and Alan Pollack and {von Eschenbach}, {Andrew C.} and Sands, {M. Elizabeth}",
year = "1995",
month = "4",
day = "30",
doi = "10.1016/0360-3016(95)00566-H",
language = "English",
volume = "32",
pages = "21--32",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - The source of pretreatment serum prostate-specific antigen in clinically localized prostate cancer-T, N, or M?

AU - Zagars, Gunar K.

AU - Kavadi, Vivek S.

AU - Pollack, Alan

AU - von Eschenbach, Andrew C.

AU - Sands, M. Elizabeth

PY - 1995/4/30

Y1 - 1995/4/30

N2 - Purpose: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. Methods and Materials: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. Results: Serum PSA level became undetectable in 277 of the 280 (99%) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values ≤ 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between ≤ 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12%). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7% and a median of 5% to the pretreatment serum value. Because such back-extrapolated values estimate the potentially maximal micrometastatic contribution, metastatic disease at diagnosis contributes little to pretreatment serum PSA. Conclusion: In patients with clinically localized prostate cancer, putative micrometastatic disease contributes negligibly to the pretreatment serum PSA level even when the latter is high. Most likely such patients, when they have metastases, have a very low metastatic burden.

AB - Purpose: Prostate-specific antigen (PSA) is an important marker for prostate cancer and has been shown to be secreted from the primary tumor and from metastases. However, the relative contribution of the primary and micrometastatic disease to the serum level of PSA in patients with clinically localized disease has not been delineated. This study addresses the source of pretreatment serum PSA in patients with clinically localized disease. Methods and Materials: The fall in serum PSA level following radical prostatectomy (280 patients; 105 T1, 165 T2, 10 T3) or definitive radiotherapy (427 patients; 122 T1, 147 T2, 158 T3/T4) was analyzed with the assumption that any fall in PSA following local treatment reflects the fraction of PSA produced in the prostate and its primary tumor. Results: Serum PSA level became undetectable in 277 of the 280 (99%) patients within 6 months of radical prostatectomy. The three patients who did not achieve undetectable levels had postsurgical values ≤ 0.9 ng/ml. Following definitive radiotherapy, nadir serum PSA values were between ≤ 0.3 and 20.3 ng/ml, with mean and median values of 1.9 and 1.2 ng/ml, respectively. Nadir PSA was undetectable in 52 patients (12%). Four patients' PSA did not fall, but rose from the start, and each developed metastatic disease within 9 months, and in each metastases appeared to contribute to pretreatment serum PSA. In the remaining patients, the maximal factor by which PSA fell to its nadir was higher the higher the pretreatment PSA level. We present arguments that this is most consistent with the hypothesis that virtually all detectable pretreatment serum PSA derives from the primary tumor. Confirmatory evidence that little of the pretreatment serum PSA came from metastases was obtained by extrapolating the rising PSA profile in 97 patients back to pretreatment time. Back-extrapolated PSA contributed a mean of 7% and a median of 5% to the pretreatment serum value. Because such back-extrapolated values estimate the potentially maximal micrometastatic contribution, metastatic disease at diagnosis contributes little to pretreatment serum PSA. Conclusion: In patients with clinically localized prostate cancer, putative micrometastatic disease contributes negligibly to the pretreatment serum PSA level even when the latter is high. Most likely such patients, when they have metastases, have a very low metastatic burden.

KW - Prostate cancer

KW - Prostate-specific antigen

KW - Radiation therapy

KW - Radical prostatectomy

UR - http://www.scopus.com/inward/record.url?scp=0028918217&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028918217&partnerID=8YFLogxK

U2 - 10.1016/0360-3016(95)00566-H

DO - 10.1016/0360-3016(95)00566-H

M3 - Article

VL - 32

SP - 21

EP - 32

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 1

ER -