Calculated Cancer Volume Combines Information From Pathologic Stage and Pretreatment Parameters

ABSTRACT: Information from pathologic stage and pretreatment clinical parameters-prostate-specific antigen (PSA), Gleason score, and clinical stage-can be incorporated into a single construct-calculated prostate cancer volume. It is represented by the quotient of the cancer-specific PSA and the PSA measured in serum per cm3 of prostate cancer of a given Gleason score, where cancer-specific PSA is defined as PSA corrected for the PSA contributed by benign prostatic epithelial cells. This construct has been shown to be superior to PSA in predicting both the pathologic prostate cancer volume and pathologic stage T3 disease in patients with clinical stage T1 and T2 disease. From analyses of two data sets, the proposed new staging system appears to incorporate the predictability of both pathologic stage and several important pretreatment clinical parameters. The system may be useful in selecting the optimal local therapy or defining the role of adjuvant therapies in an individual patient. [Oncol News Int 6(Suppl 3):7-8, 1997]

Introduction

A proposed staging system based on calculated prostate cancer volume “appears to predict the important information that one gets from pathologic stage, while also incorporating the pretreatment clinical information,” Anthony V. D’Amico, MD, PhD, concluded after reviewing data from two large surgical data sets at the First Sonoma Conference on Prostate Cancer. Dr. D’Amico is with the Joint Center for Radiation Therapy at Harvard Medical School.

Calculated prostate cancer volume is represented by the quotient of the cancer-specific PSA and the PSA measured in serum per cm3 of prostate cancer of a given Gleason score. Cancer-specific PSA is defined as PSA corrected for the PSA contributed by benign prostatic epithelial cells.

The construct was developed by Dr. D’Amico and statistically analyzed by Kathleen Propert, PhD. It subtracts, from the PSA, the amount of PSA that is estimated to come from the benign component of the gland.”

Addresses Staging System Flaws

A proposed staging system based on calculated prostate cancer volume and PSA is intended to address the shortcomings of the 1992 American Joint Committee on Cancer staging system to provide clinically useful information concerning outcome for patients with localized prostate cancer—T1 and T2.

“There are six clinical stages—T1-a/b/c—T2-a/b/c, but there are not six discrete outcomes projected by those,” Dr. D’Amico explained. “It doesn’t appear from any data series I’ve seen, that this staging system segregates patients appropriately.”

Combining the Best of Both

 Reviewing data from previous studies positioned Dr. D’Amico to generate the following hypothesis: “Pathologic stage is predictive. Even when you account for PSA, Gleason score, and clinical stage, pathologic stage is still important. But pathologic stage is not the only thing that’s important, because even in patients who have pathologic organ-confined disease, there are people, based on their pre-op PSA, who don’t do as well.”

“So what we need in a clinical staging system is something that gives us the predictability of pathologic stage, and still incorporates the important pretreatment clinical parameters—namely pre-op PSA, and biopsy Gleason score. We need to put these things together.”

System Applied to Surgical Data

The usefulness of calculated prostate cancer volume was studied among 104 patients treated with a radical retropubic prostatectomy at the Brigham and Women’s Hospital in Boston. Calculated prostate cancer volume was determined based on PSA, Gleason score, and ultrasound determined prostate volume. The calculated prostate cancer volume was compared to pretreatment PSA, biopsy Gleason score, and clinical stage, in predicting pathologic stage T3 disease in patients with clinically organ-confined disease. “Everything on univariable analysis, except clinical stage predicted pathogic T3 disease,” Dr. D’Amico reported, “but on multivariable analysis, only the calculated cancer volume construct remained predictive.”

The construct was then used with a larger group of patients—725 patients with clinical stage T1 and T2 disease who were surgically treated at the University of Pennsylvania. The median follow-up was 3 years and the end point was time to postoperative PSA failure. The variables were PSA, Gleason score, clinical stage, and calculated prostate cancer volume.

The results of that analysis allowed Dr. D’Amico to construct a staging system based on calculated prostate cancer volume (cV_Ca) and PSA. “My idea of a staging system,” Dr. D’Amico said, “is one on which you can base treatment decisions for an individual patient before treatment is instituted.”

Proposed Staging System Tested

Dr. D’Amico compared the proposed staging system to pathologic stage in the Penn data set and the Brigham and Women’s surgical data set. A Cox regression multivariate analysis was performed and Akaike’s Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) estimates, which are two comparative measures, were calculated to test the relative ability of each staging system to predict time to postoperative PSA failure. Bootstrapping analysis was performed to ascertain whether numerical differences in outcome prediction were truly statistically different.

The results showed “the two staging systems [proposed clinical staging system based on cV_Ca and PSA and the 1992 AJCC pathologic staging system] were equally predictive of postoperative outcome” in the Penn data set and “in the Brigham data set, the clinical staging system based on cVCa and PSA was actually better,” Dr. D’Amico said.

“What it basically means,” Dr. D’Amico explained, “is that this calculated construct and PSA, in these two data sets, provided information regarding postoperative outcome that was at least as good as pathologic stage, and maybe a little bit better in one of the surgical data sets.”

He based the last assertion on Kaplan-Meier curves for the Penn data. “I looked at pathologic organ-confined, microscopic extracapsular extension (ECE), macroscopic, and seminal vesicle involvement,” Dr. D’Amico said. “And, interestingly, what falls out here, is that the macroscopic ECE and seminal vesicle invasion do similarly poorly, whereas the microscopic ECE do better. And if you look at the outcome prediction based on the calculated cVCa and PSA staging system, the break points are much better.”

What’s Next?

“So in these two data sets, what one can say is that you have a staging system that appears to predict the important information that one gets from both pathologic stage, and the pretreatment clinical information. And that seems to be clinically useful,” said Dr. D’Amico.

“Once we have this information ahead of time, then what do we do with it? This proposed staging system helps us to determine the optimal local therapy and also allows us to select patients for adjuvant therapies that should be given in a situation of a phase II or III trial” said Dr. D’Amico, who added that the proposed staging system needs to be validated in other series.