PiA Trial: a Cross-sectional, Multicenter, Consecutive Cohort Evaluating the Distribution of uPA/PAI-1 Versus St. Gallen Algorithm in >1000 Prospectively Included Patients
The determination of the prognostic factors uPA/PAI-1 (further: "biological") is established
and recommend by recent guidelines. However, so far data can only show their independent and
strong prognostic influence. The absolute proportion of patients, which profit from the
improved risk assessment, is only estimated from old trials with different patient
Depending upon assessment, the proportion of low risk patients by traditional risk
assessment is 20 - 40%, by biological assessment 35 - 55% of all node negative patients. The
data from investigations of historic populations are not reproducible now because of smaller
tumor size at presentation due to diagnostic procedures (Screening, good public promotion).
The effectiveness and clinical relevance of the risk assessment were already confirmed for
the biological prognostic factors uPA/PAI-1 in node negative breast cancer in several
retrospective and prospective trials as well as in a meta-analysis. Still these biological
factors (or others!) are not yet established into nationwide clinical routine in Germany.
This is due to higher expenditure of this method for the primary therapy (uPA/PAI-1 is
determined in the shock-frozen tissue), on the other hand due to the absence of
reimbursement. Therefore presently in many centres risk estimation and associated therapy
decision is done by traditional assessment.
In order to justify the higher expenditure and the additional costs by the
uPA/PAI-1-determination, not only the clear proof of the advantage for the individual
patient, but also the estimation of the extent of this advantage in all applicable patients
A first goal of this project is to compare the respective proportion of patients allocated
as high- or low-risk by means of biological and also traditional prognosis factors in a
defined consecutive patient cohort. The determination of uPA/PAI-1 should be established as
standard procedure in the future.
So far, the question discussed above referred mainly to patients with node negative breast
cancer. In this group, the largest effect in saving chemotherapy is to be expected. Due to
previous results we assume that also in node positive patients adjuvant chemotherapy may be
saved in sub-group because of very small risk of recurrence. Therefore the determination of
uPA/PAI-1 for this group of patients will also be done at the end of this study.
A second goal of this project is it to collect data for risk assessment in node positive
patients to be able to offer assistance in the future to perhaps give a better estimation of
the individual risk of recurrence.
Practically fresh frozen tissue will be taken, shock-frozen and stored from all consecutive
patients operated in the five participating hospitals. The determination of uPA/PAI-1 will
be performed in the research laboratory of department of Gynaecology at the University
Hospital in Halle (Saale).
A third goal is it to provide biological risk assessment by giving results of uPA/PAI-1
testing promptly to participating node negative patients. This information will be crucial
in their decision for or against chemotherapy.
Amendment 2 from June 12, 2012 (Steering committee E Kantelhardt, M Vetter, Ch Thomssen)
A) Established prognostic factors (RNA level) will be evaluated in the context of uPA/PAI-1
and immunohistochemistry markers on samples from the frozen and FFPE tissue. The list of
genes is submitted to the Ethics sommittee.
B) Eplorative analysis of these factors concerning response to therapy will be done.
C) Follow-up information will be collected after a minimum observation time of 2.5 years for
all patients (in October 2013).
Observational Model: Cohort, Time Perspective: Prospective
Event free survival
All patients will be followed after a minimum observation time of 2.5 years.
2.5 years minimum observation time
Eva J Kantelhardt, MD
Gynecology Martin Luther Univ Halle/Germany
Germany: Federal Institute for Drugs and Medical Devices