Clínica de Urologia Dr. Charles Rosenblatt

Based on information provided by
www.prostatepointers.org
the Memorial Sloan-Kettering Cancer Center
and the
European Organisation for Research and Treatment of Cancer (EORTC)

Partin's Predictions: What Do They Really Mean?

Jonathan R. Oppenheimer, MD, FCAP
Chief Pathologist and Medical Director
Oppenheimer Urologic Reference Laboratory

The 1997 edition of the so-called Partin tables represents a remarkable joint effort of three major academic centers of prostate cancer excellence. Data from 4133 men who had undergone radical prostatectomy (RP) were collected from Johns Hopkins Hospital, the University of Michigan, and the Baylor College of Medicine. These data were analyzed to determine the value of combining readily obtainable pre-operative information (PSA, Clinical Stage, Gleason score) in predicting the extent of the actual tumor as determined by post-surgical pathological exam. The large amount of data collected and tabulated in several charts allows patients and their physicians to more accurately estimate the probability that surgical intervention will result in complete removal of the tumor.
The application of these tables allows the patient and physician to arrive at a more informed treatment decison and encourages more frank discussion regarding the benefits and risks of possible treatments. In order to appreciate the relevance of the Partin tables, however, it is important to understand what they predict rather than what they are assumed to predict.
A major misconception in the minds of many is that the Partin tables predicts whether or not RP will be curative. Leaving aside the semantic argument of whether or not "cure" is an acceptable term for a disease that can recur many years after having been apparently successfully treated, the Partin tables predicts the results obtained on pathologic exam of the prostate and lymph nodes after surgery. While there is a logical and scientifically proven correlation between the results of pathologic evaluation and the patient's prognosis, these two end-points are quite different. The divergence between the pathology and prognosis can be attributed to several factors:
Some tumors which are organ-confined on pathologic exam are not organ confined in reality. In spite of the main mass of the tumor having been removed, metastatic deposits of tumor may have already been deposited in other parts of the body. Alternatively, since the pathologic examination of the prostate entails the review of multiple planes of tissue taken from a roughly spherical organ, the point of capsular penetration by the tumor may be missed on microscopic examination.
Some tumors which demonstrate capsular penetration on pathologic exam are taken from patients who do not show signs of biochemical (detectable PSA) or clinical (symptomatic) recurrence many years after surgery. In a study of 721 men at Johns Hopkins, 58% of men with clear-cut capsular penetration had no evidence of biochemical recurrence ten years after surgery . Post-surgical manipulation of the RP specimen may induce tissue changes (artifacts) that are mistaken by the pathologist as evidence of disease extension. Perhaps inflammation or loss of local blood supply induced by the surgery may somehow induce the regression of a small amount of tumor left inside the patient. In view of the above, it is understandable why some surgeons may not wish to deny their patients an attempt at possible curative therapy even when faced with a substantial probability of predicted non-organ confined disease.
Patients may benefit from the removal of the great majority of their tumor (so-called tumor debulking) and achieve longer life and decreased symptoms even though not all of the cancer was removed. It has been shown that in patients with no high-grade disease on biopsy radical prostatectomy can be beneficial even in the presence of locally invasive disease or seminal vesicle invasion . The value of tumor debulking is controversial and must be weighed against the benefits of treatment alternatives with less detrimental effect on the patient's quality of life.
It must be kept in mind that the Partin et al assume that it is the post-operative pathologic stage which is of foremost importance in assessing prognosis. Other investigators have found pre-operative PSA, Gleason grade , and DNA ploidy to be better predictive of eventual outcome than pathologic stage.
Although the Partin tables can help to better evaluate therapeutic options, it must always be remembered that these tables use statistical data to predict probable outcome in an individual. Utilizing these tables may lead to the acquisition of more "knowledge" that may leave one with the feeling of even more uncertainty. We should also take into account other pre-operative prognostic data derived from the individual patient: the number and laterality of biopsy cores involved with cancer, the percentage of high grade cancer in biopsies , pathologic staging , DNA ploidy analysis, microvessel density , tumor proliferative markers, endorectal coil and spectroscopic MRI imaging , radionuclide (Prostascint) studies , etc. The efficacy and cost-effectiveness of the above-mentioned tests are unfortunately not known at present. Nevertheless, the Partin tables remain an extremely useful tool for empowering the thoughtful patient and physician dealing with prostate cancer.
Jonathan R. Oppenheimer, MD, FCAP
September 29, 1997

Partin's Predictions: 2001

Alan Partin
Johns Hopkins University, USA

Urologist Alan Partin is a household name, right up there with Donald Gleason, the pathologist for whom the grading system for prostate cancer is named.
The Partin Tables were developed at the Brady Urological Institute in 1993 by Partin and urologist-in-chief Patrick Walsh, after Partin studied the course of prostate cancer in hundreds of Walsh's radical prostatectomy patients. The tables correlate those three key pieces of the prostate cancer puzzle with the actual pathologic stage, determined when pathologist Jonathan Epstein, M.D., examined the surgically removed prostate specimens. With 95-percent accuracy, they predict a man's likelihood of being cured by treatment. In the span of a few years, these tables have become indispensable for many patients as well as doctors trying to chart the right course of treatment in a sea of confusing choices.
The 2001 Partin Tables are based on the results of 5,079 men who underwent surgery at the Johns Hopkins Hospital between 1994 and 2000. They're also more consistent; while earlier Partin Tables had included patients from other hospitals, these don't.
The 2001 tables are broader, too. Earlier versions of the Partin Tables divided PSA into broad ranges: 0-4, 4-10, 10-20, and higher than 20. The 2001 tables also include two categories for Gleason 7. This is because not all Gleason 7 cancers are alike. There is a difference between Gleason 3 + 4, where most of the tumor is Gleason grade 3, and Gleason 4 + 3, where more of the tumor is Gleason 4. Gleason 4 + 3 tends to act more like a Gleason 8, but Gleason 3 + 4 tends to act more like a Gleason 6.

Abstract # 952, Presented at the 2001 AUA Conference, Anaheim, CA

CONTEMPORARY UPDATE OF PROSTATE CANCER STAGING NOMOGRAMS (PARTIN TABLES) FOR THE NEW MILLENNIUM Alan W Partin*, Patrick C Walsh, Jonathan I Epstein. Baltimore. MD; Jay D Pearson. Rahway. NJ

Introduction and Objectives: We previously presented nomograms combining pre-operative serum tPSA clinical (TNM) stage, and biopsy Gleason Score to provide the likelihood of various final pathological stages at radical prostatectomy (RRP) (Partin et al. JAMA 277: 1445, 1997). Data for the original nomograms were collected from men treated between 1982 and 1996. Over the past five years, stage at presentation has shifted with more men presenting with stage T1c, Gleason score 5-6 and serum PSA levels less than 10.0 ng/ml. In this work we update the 'Partin Tables' with a more contemporary cohort of men treated since 1994 with revised PSA and Gleason categories.

Methods: Multinomial log-linear regression was used to estimate the likelihood of organ confined, capsular penetration, seminal vesicle or lymph nodal status on pre-operative PSA stratified as (<2.5, 2.5-4.0., 4.1-6.0, 6.1-10.0, >10), Clinical (TNM) stage (T1c, T2a, T2b, or T2c) and biopsy Gleason score stratified as (2-4, 5-6, 3+4=7, 4+3=7 or 8-10) among 5,079 men treated with RRP (without neoadjuvant therapy) between 1994 and 2000 at The Johns Hopkins Hospital. Average age was 58 years.

Results: In this cohort, >60% were T1c, >75% were Gleason score 6, >70% had a PSA >2.5 and <10.0 ng/ml, and >60% had organ-confined disease. Nomograms of the robust estimated likelihoods and 95% confidence intervals were developed from 1000 bootstrap analyses. The improved outlook for this contemporary cohort will be highlighted.

Conclusions: These updated 'Partin Tables' were generated to reflect the trends in presentation and pathological stage for men newly diagnosed with clinically localized prostate cancer at our institution. Clinicians can use these nomograms to counsel individual patients and help them make important decisions regarding their disease.

TNM Classification (1992)

Yet another staging system for prostate cancer has been used for a long time, mainly in the United States. It was developed under the auspices of the American Urological Association (AUA). The ABCD-system has been taken over by the TNM-system over the years and has been used world-wide in trials. It allows for a much greater, and therefore more accurate differentiation in tumor stages. Knowledge of the ABCD-system, however, may still come in handy to be able to compare 'old' and new studies.

ABCD SYSTEM	TNM SYSTEM	DESCRIPTION
A1	T1a N0 M0	Tumor is an incidental histologic finding and is seen <= 5% of resected tissue
A2	T1b N0 M0	Tumor is an incidental histologic finding and is seen > 5% of resected tissue
B1	T2a-b N0 M0	Palpable nodule in one lobe but < 1.5 cm in diameter
B2	T2c N0 M0	Larger palpable nodule
C1	T3a-b N0 M0	Tumor invades capsule of prostate
C2	T3c N0 M0	Tumor invades seminal vesicle
D1	T1-4 N+	Metastases to regional lymph nodes, or extensive regional spread
D2	T1-4 M+	Evident distant metastases
D3	T1-4 M+	Recurrence after endocrine therapy

(based on information compiled by Dr. R.C.M. Pelger, Leiden University Hospital, Leiden, The Netherlands, and other sources)
Pathological grading according to Gleason is based on a VACURG (Veteran's Administration Cooperative Urological Research Group) study on 4000 patients between 1960 and 1975. Grading is based on the amount of glandular differentiation. The differences in tumor tissue structure (heterogeneity) is taken into acoount by scoring a primary pattern for the dominant grade and a secondary pattern for the non-dominant grade. Both yield a score of 1-5, which are then combined to a total Gleason Score. On average, two or more grade patterns can be seen in a pathologic specimen.
The resulting Gleason Score is then compiled in 9 groups: Gleason 2-10. For practical purposes, the Gleason Score can be divided into three groups (Gleason 2-4, 5-7, 8-10) to allow for comparison with other grading methods (like the G1-3 grading used in trials based on the TNM system of staging).
Recently, a subdivision of the Gleason Score has been propositioned. It was shown in at least one study that Gleason 3+4 may have a different prognostic outcome tha Gleason 4+3. It remains to be seen whether this, and other proposals will be incorporated into accepted grading scores, while their practical value is not yet established.
Bear in mind that Gleason Grading (1-5) is different from Gleason Score (2-10).

Like the ABCD staging is slowly being replaced by the TNM system, the G score, formerly always used in combination with the TNM Staging system, also seems to be on its way to extinction. For practical purposes, the G grading is often correlated to the Gleason score, although both systems are quite different from a pathologists view.

G	GLEASON SCORE	DESCRIPTION
Gx		Grade cannot be assessed
G1	2-4	Well differentiated (slight anaplasia)
G2	5-7	Moderately differentiated (moderate anaplasia)
G3	8-10	Poorly differentiated or undifferentiated (marked anaplasia)

High-grade Prostatic Intraepithelial Neoplasia (HGPIN): High-grade PIN is considered to be the most likely precursor of prostate cancer. It has the architectural features of benign glands but the cytologic features (i.e. cellular features) of cancer. It is a proliferative lesion (i.e. dividing more rapidly than benign glands) and shows enlargement of nuclei and nucleoli. Patients with high-grade PIN only in needle biopsy are at increased risk of developing cancer and must undergo repeat biopsy within the next 3-6 months. Studies have shown that 40% to 60% of repeat biopsies will have cancer (Davidson et al. Prostatic intraepithelial neoplasia is predictive of adenocarcinoma. Journal of Urology, 154:1295-99, 1995)

Immunohistochemical Markers in Pathology

A few immunohistochemocal markers are being used for pathologic 'coloring' in prostate carcinoma:

This is a non-specific coloring method of the cell nucleus. A brownish color means that the tissue tests positive for androgen receptors.

This is a non-specific carcinoma coloring of the cytoplasm. A brownish color means that the tissue tests positive for an epithelial malignancy.

This is a coloring of the basal cells of the epithelium of the prostate glandulae. The prostate epithelium is made up of two layers. Prostate cancer will cause the basal layer to disappear. A brownish means that the basal layer is still intact, i.e. there is no prostate cancer present.