August 22, 2014
 


NEW PARTIN NOMOGRAM - 2011

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This Brady Urological Research Institute web-based program generates the '2010 Partin Nomogram' as described in Huang et al BJUI, 2011 for each of the four prostate cancer (PCa) pathological stages. This work is based upon two PCa sample sets [(JHH with 5730 cases (the set for estimation) and University Clinic Hamburg-Eppendorf (UCHE) with 1646 cases (the set for validation)], and the analysis models the risk of a PCa patient-based on his individual continuous PSA measurement, clinical stage, and biopsy Gleason score, and hence represents an extension of the 2007 Partin Table (Makarov DV et al, 2007) where PSA categorical groups are utilized.

Prognostic factors

In addition to prostate cancer stage, urologists use other prognostic factors to help plan the best treatment and predict how successful treatment will be. Below are key 'prognostic factors' for patients with prostate cancer.

PSA test.
Total PSA is a measurement of prostate-specific antigen (PSA) levels in a man's blood. PSA results are usually reported as nanograms (mass or weight) per milliliter (ng/ml) [volume]. For example a value of 4 ng/ml would mean a total PSA level of "4". Often men already diagnosed with prostate cancer by biopsy, the clinical stage determined by digital rectal examination (DRE), the PSA level and the biopsy Gleason score (described below) helps the urologist understand and predict a patient's prognosis and assists the doctor and patient to make more informed treatment decisions. Occasionally some prostate cancers do not cause an abnormal or increased PSA level; hence a normal total PSA does not always mean that there is no prostate cancer. In order to utilize the new 'Partin Nomogram' a patient or urologist must have the patient's total PSA value (number), DRE results or clinical stage, and the biopsy Gleason score.

gleason system prostate cancer

The Gleason System

for prostate cancer grading is based on how much the cancer looks like healthy (benign) tissue when viewed under a microscope by a pathologist (M.D., specialist that diagnosis diseases at the tissue level). Less dangerous prostate tumors have a appearance of healthy glandular tissue, and more aggressive tumors that are more likely to invade and spread to other parts of the body look less like healthy tissue with respect to their loss of normal glandular architecture and changes in the cell's nuclear structure (See the Figure to the right).

The pathologist assigns a 'score' on a scale of Gleason grade 2 to 5. The Gleason grading system (tissue and cellular changes indicative of cancer) and tumor stage (pathologic extent of disease inside the gland and if it has spread outside the gland) have served as independent and clinically significant 'prognostic factors' which can predict biochemical recurrence, metastasis, and overall patient survival. Prostate cancer glands and cells that appear to be healthy cells (benign) are given a low Gleason grade, and cancer cells that look less like healthy cells are given a higher Gleason grade.

To assign a Gleason score, the pathologist first looks for a dominant (primary) pattern of cell growth or grade (area where the cancer is most prominent) and then looks for a less widespread pattern or grade (secondary) of growth, and gives each one a grade number.

The Gleason score (GS) is the sum of the dominant or primary tissue pattern grade (representing the majority of tumor; see the embedded figure) and the less dominant or secondary tissue pattern grade (assigned to the minority of the tumor), resulting in a Gleason score or sum ranging from 2 to 10.

Today, urologists tend to describe a Gleason score of 6 as a low-grade cancer, 7 (3+4 or 4+3) as medium-grade, and 8, 9, or 10 as high-grade cancer. A lower-grade cancer grows more slowly and is less likely to spread than a cancer with a higher grade. An experienced uropathologist should read and interpret the prostate tissue samples from either the biopsy or the radical prostatectomy specimens to assure an accurate Gleason score.

Gleason X: The Gleason score cannot be determined.
Gleason 6 or lower: The cancer cells are well-differentiated.
Gleason 7: The cancer cells are moderately differentiated. Primary Gleason grade may be 3 or 4.
Gleason 8, 9, or 10: The cancer cells are poorly differentiated or undifferentiated.

Clinical staging

The clinical stage is based on the urologist's clinical examination of the patient's prostate (via palpation or DRE) and this is combined with other results of tests done prior to definitive treatment (i.e. surgery or irradiation). The DRE involves digital palpation of the gland for size and any abnormalities. Based on these results, the urologist may suggest performance of a systematic biopsy of the gland to determine a diagnosis. Additionally, the urologist may suggest possibly X-rays, CT scans, and bone scans. X-rays, bone scans, and CT scans, but these tests may not always be needed. They are usually recommended based high levels of serum PSA as well as the biopsy Gleason score and/or volume (size) of the cancer.

The clinical stage of the prostate cancer is described below:

T1: The tumor cannot be felt during the DRE and is not seen during imaging (any test that produces pictures of the inside of the body, such as a CT scan). It may be found when surgery is done for another reason, usually for BPH, or abnormal growth of benign prostate cells.

T1c:
The tumor is found during a needle biopsy, usually because the patient has an elevated PSA level.

T2:
The tumor is found only within the prostate, not other areas of the body. It is large enough to be felt during the DRE.

T2a:
The tumor has invaded one-half of one lobe (part or side) of the prostate and may be palpated during the DRE.

T2b:
The tumor has spread to more than one-half of one lobe of the prostate, but not to both lobes and may be palpated during the DRE.

T2c:
The tumor has invaded both lobes of the prostate and may be palpated during the DRE.

Pathological Staging

Following surgery to remove the prostate gland, a pathologist will assign the Gleason score and stage (extent of the size and spread of the cancer).  They utilize the standardized T, N, and M classification to define TNM combinations to describe each stage of prostate cancer. The TNM is an abbreviation for tumor (T), lymph node (N), and metastasis (M) to lymph nodes and/or bone or other organs. Urologists look at these three parameters to determine the stage (extent) of cancer:

Prostate Cancer Pathologic Stage Grouping Chart (Current system)

Stage

T

N

M

I

T1a, T1b, or T1c

N0

M0

 

T2a

N0

M0

 

Any T1 or T2a

N0

M0

IIA

T1a, T1b, or T1c

N0

M0

 

T1a, T1b, or T1c

N0

M0

 

T2a

N0

M0

 

T2b

N0

M0

 

T2b

N0

M0

IIB

T2c

N0

M0

 

Any T1 or T2

N0

M0

 

Any T1 or T2

N0

M0

III

T3a or T3b

N0

M0

IV

T4

N0

M0

 

Any T (lymph nodes +)

N1

M0

 

Any T

Any N

M1


From: Dr. PC Walsh, Guide to surviving prostate cancer.
2nd Ed. Wellness Central, New York and Boston, 2007

The new Partin Nomogram Defines Pathological Stages (Extent of Disease) as:

Organ Confined Prostate Cancer (OC) – Within the prostate gland

Extracapsular Extension (ECE)
– Tumor has broken through the capsule of the prostate gland.  This is not inoperable prostate cancer necessarily.  Also it can be referred to as extraprostatic Extension (EPE).

Seminal Vesicle (SV) -
The tumor has spread to the seminal vesicles adjacent to the prostate (see image).

Lymph Nodes (LN)
- The tumor has spread to the lymph nodes near the prostate gland.

 

<< Prev 1 2 3 4 5 Next >> For a better understanding of the Partin Nomogram browse the information above

INDIVIDUAL PREDICTION RISK

Given three input values (PSA, clinical stage, and Gleason score), we return estimated probability (likelihood) as a percentage value of being in each of the four pathological stages (Organ confined, Extraprostatic extension, Seminal Vesicle Invasion, Lymph Node Invasion). The software program below generates % individual risk and in addition, the 95% confidence intervals are also returned.  Figure 3 from the BJUI article shows the graphs from which the software program was generated for N=5730 prostate cancer cases.



Key References:
  1. Huang, Y., Isharwal, S., Haese A., chun, F. K. H., Makarov, D. V., Feng, Z., Han, M., Humphreys, E., Epstein, J. I., Partin, A. W., and Veltri, R. (2010) Prediction of patient-specific risk and percentile cohort risk of pathological stageoutcome using continuous prostate-specific antigen measurement, clinical stage, and biopsy Gleason score. BJUI 107, 1562-1569.

  2. Makarov DV, Trock BJ, Humphreys EB et al. Updated nomogram to predict pathologic stage of prostate cancer given prostate-specific antigen level, clinical stage, and biopsy Gleason score (Partin tables) based on cases from 2000 to 2005. Urology 2007; 69: 1095-101

Acknowledgements:
The statistical R-program was prepared by Dr. Ying Huang, Fred Hutch Cancer Research Center (FHCRC). Greta Stoianovici (JHH Brady Urology Webmaster) transformed the R-program into the final formatted user- friendly nomogram. Dr. Robert Veltri organized the research study and assisted in the final design of the Partin Nomogram.

RISK DISTRIBUTION ESTIMATION

For a given pathological stage (Organ confined, Extraprostatic extension, Seminal Vesicle Invasion, Lymph Node Invasion), we estimated the distribution of the risk (probability of being in this pathological stage) for patients in the entire JHH cohort (N=5730).

Figure 4 -y coordinate is p , x coordinate is v
               (0,1)=(0%,100%))
from the BJUI paper shows the risk quantile curve for each pathological stage and their 95% CI.

First, given two input values (pathological stage, and a value p in (0, 100%)), the software program below returns the estimated proportion of subjects in the JHH cohort with the probability (likelihood) of being in this pathological stage less than p, together with its 95% confidence interval. For example, if we enter p as the probability of being Organ Confined for an individual patient deter mined from the left side Table, then the output will show the proportion of subjects in the JHH cohort with smaller probability of being Organ Confined compared to this patient, in other words the placement of the patient's risk of being Organ Confined relative to others in the JHU population.

Second, given two input values (pathological stage, and a value v in (0, 100%)), the software program below returns the vth percentile of the probability of being in this pathological stage in the entire JHH cohort and its 95% confidence interval.  For example, if one select Organ Confined and a low v1=5% to get one output, and then select Organ Confined and a high v2=95% to get another output.  The two outputs will provide the 5th to 95th percentiles of the probability of being Organ Confined in JHU population.



 

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