Are Cure Rates Reliable?

The SURVIVAL benefits between the four definitive treatment options (HIFU, cryoablation, radiation, surgery) for localized prostate cancer are similar.
Survival,does not necessarily equate with CURE. Cure rates for prostate cancer have to be viewed with considerable caution simply because the data points used to generate the prostate cancer stage are inexact and this information is used to generate a cure rate.

This inexactness comes about from the fact that the data points are often affected by physician subjective interpretation and these data points therefore, cannot be definitive.

In addition,many studies arbitrarily define cure from prostate cancer as having a PSA of 0.1-0.2ng/ml.. However,this definition is not always absolute as some treated men may have a more elevated but stable PSA with a prostate biopsy showing no residual disease.

The staging system used customarily to classify the extent of a man’s prostate cancer is the TNM system where T stands for Tumor,
N stands for Nodes and M stands for Metastases.

With respect to the T component of the TNM clinical staging system,arbitrarily,only the the results of the digital rectal examination (DRE) and the trans-rectal ultrasound (TRUS),but not the results of the needle biopsy that accompany the TRUS, are used.

Because of the limitations of the TNM staging system for determining the true extent and nature of a man’s prostate cancer,additional but also indefinite data points are often combined with the man’s clinical prostate cancer stage in an an attempt to generate more meaningful cure rates. These extra data points come from examining the patient’s risk for cancer progression (see D’Amico) by factoring in his PSA as well as the histological results from his prostate biopsy.
Lets consider now the relative accuracy and reliability of the data points that are used to establish the stage of a man’s prostate cancer as well as his risk for cancer progression as this information is used to generate the cure rate.

1. Digital rectal examination (DRE)

The purpose of this exam is to find a nodule or an area of induration in the prostate as this may represent an area of cancer. This physical examination however has about a 50% accuracy,about as good as tossing a coin.

2. Serum Markers

a). prostatic specific antigen (PSA)

The total PSA (with normal values less or equal to 4ng/ml) on it’s own, is NOT A RELIABLE indicator of a possible prostate cancer.
The PSA can be LOWERED by medicines such as STATINS/NSAIDS/THIAZIDE DIURETICS and 5 ALPHA REDUCTASE INHIBITORS such as proscar and avodart. This may not mean a lowered risk for prostate cancer.

The PSA can be raised because of a large prostate,by a urinary tract infection, prostatic inflammation or infection,after ejaculation, a prostate biopsy and after a DRE.

About 30% of men who have a PSA between 4-10ng/ml will have a prostate cancer but about 70% will not.

Also, about 30% of men who have a PSA UNDER 4 will have a clinically significant but organ confined prostate cancer.

The use of the PSA profile and %free PSA may improve the accuracy of prostate screening for cancer.

An ABNORMAL PSA should always be RECHECKED with a repeat study to exclude spurious laboratory results.

b). acid and alkaline phosphatases

These serum markers are only useful in confirming suspected advanced prostate cancer.

3. Imaging

The following studies are commonly undertaken in the evaluation of prostate cancer but they are affected by considerable physician subjective interpretation.
a).Trans Rectal Ultrasound (TRUS)

This study is done for volume estimation of the prostate as well as in association with a needle biopsy for diagnosis.

Only some prostate cancers are visible as hypoechoic peripheral zone lesions and only about 20% of these areas harbor cancer.

This is the reason why a systematic sextant random needle biopsy sampling of the prostate is so important.

As well,the sonography may also identify local extension or invasion of prostate cancer to adjacent structures. This aspect of sonography has only about a 60% accuracy and even less so when trying to determine seminal vesicle invasion.

Transrectal ultrasonography is also operator dependent and has generally, poor sensitivity and specificity.

b). CT and Bone scans

These imaging studies are affected by physician subjective interpretation a great deal and are generally not useful in men with a PSA below 20ng/ml as the studies are invariably normal. Furthermore,these studies are limited by their inability to detect microscopic spread or early local invasion of adjacent structures and therefore under staging the prostate cancer is problematic.

c). magnetic resonance imaging (MRI)

This study is often performed in association with an endo rectal coil. The MRI imaging has also similar limitations to those listed above.
d). prostascint scan

This scan is rarely used now because of the many false positive and false negative interpretations.

4. Staging Lymphadenectomy

Not often performed anymore and was used to provide information for the N category of the TNM staging system. It was undertaken as the first stage of an anticipated radical prostatectomy,particularly in those men where spread to the lymph nodes was suspected. Two variations of the lymph node dissection were done,limited or extended. Most often,if the frozen section examination of the nodes by the pathologist indicated cancer then the surgical procedure was abandoned and radiation was offered to the patient. However,the frozen section studies were not entirely accurate and some nodes that were initially read as negative were later found to contain cancer when examined by permanent section.

5. Trans Rectal Needle Biopsy

This procedure is usually combined with the TRUS.

The majority of the prostate biopsies are performed in the urologists office as a 12 core sextant random needle biopsy under local anesthetic. This process randomly samples a small volume of prostate and the procedure has about a 30% false negative rate.

As well,the 12 core biopsy is a relatively poor predictor of tumor extent. However,the saturation biopsy with at least 20-25 cores may improve accuracy. Furthermore,both biopsy procedures are operator dependent in that errors can be generated by inappropriate sampling and taking core samples of inadequate length. In addition, other issues can impact the assessment of the prostate such as, specimen contamination from one needle core site to another site,crush artifact,incorrect specimen labeling with respect to side and site of the prostate, mishandling during transportation and or mishandling in laboratory.

6. Pathology Report

The majority of the prostate needle biopsy specimens performed by urologists are read by general pathologists.

Because there is a considerable degree of physician subjectivity involved in the reading and interpreting the prostate biopsy specimens there can be a considerable difference of opinion between pathologists as to the diagnosis. Even with the use of the specialized triple immunohistochemistry stains.
This concern for reliability can extend to the most fundamental and that is, does a cancer exist? Other differences of opinion are not uncommon with respect to the amount of prostate cancer,the Gleason score and the presence of precursor lesions such as high grade prostatic intraepithelial neoplasia (HGPIN) and atypical small acinar proliferation (ASAP).

Over the years I have seen many patients get vastly different diagnostic readings on the same biopsy specimens from different pathologists. Even a different reading from the same pathologist when the prostate biopsy slides were re read some time later.

Because of this great concern for accurate interpretation of the prostate biopsy it is imperative that all prostate biopsies be sent for VALIDATION to an independent reference laboratory that specializes in prostatic diseases.

By doing so we can be reasonably assured that we have a creditable understanding of the results of the prostate needle biopsy.

Summary

All of the data points used to determine a man’s prostate cancer stage and his risk for prostate cancer progression have issues concerning subjectivity,reliability and accuracy. Because published cure rates for prostate cancer are a function of these indefinite data points,limitations to the accuracy of the cure rates for prostate cancer are obvious.

Therefore,comparisons of cure rates between various treatment modalities are suspect. Even more,many of these published cure rates after prostate cancer treatment lack independent verification and this obviously represents a conflict.

Finally,because of continued evolution and improvement in technology,the cure rates after treatment for localized prostate cancer reported 5-10 years ago may not be representative of cure rates today.

So, are cure rates for treatment of localized prostate cancer reliable? No, and they need to be viewed very cautiously.