To All

Here are several interesting studies. One is about "insignificant" tumors and how to identify them. The second is the curing of PCa based on age.Remember both of these have to do with men who have had RP's probably from Walsh as they are Johns Hopkins studies.

An additional post from Dr. Strum about a patient who has low PSA's

My comments follows the abstracts. These comments are based on doing surgery for curative purposes. If you have high risk or systemic disease (or believe you have systemic disease) you may want to consider surgery as a method of debulking the tumor load and getting rid of the primary tumor. If this is your decision you should immediately consider additional treatments of radiation, hormonal ablation therapy and chemotherapy. The idea to remove the gland when you have systemic disease is controversial and some doctors may advise against doing surgery.

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Insignificant Disease

Nonpalpable stage T1c prostate cancer: prediction of insignificant disease using free/total prostate specific antigen levels and needle biopsy findings.

Epstein JI, Chan DW, Sokoll LJ, Walsh PC, Cox JL, Rittenhouse H, Wolfert R, Carter HB

Department of Urology, The Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland 21287, USA.

PURPOSE: Approximately 25% of radical prostatectomies performed for stage T1c disease show potentially insignificant prostate cancer. We previously reported the use of serum prostate specific antigen (PSA) density and needle biopsy findings to predict potentially insignificant cancer. We now evaluate whether using free/total serum PSA levels along with needle biopsy findings can better predict tumor significance. MATERIALS AND METHODS: We studied 163 radical prostatectomy specimens of stage T1c prostate cancer in which free/total serum PSA levels were determined. Free/total serum PSA levels were measured with Tandem-MP PSA assays. Insignificant prostate cancers were organ confined with tumor volumes less than 0.5 cc and Gleason score less than 7. Advanced tumors were either Gleason score 7 or greater, established extraprostatic extension with positive margins, or positive seminal vesicles or lymph nodes. Other cases were considered as moderate tumor. Moderate and advanced tumors were considered significant. RESULTS: Of the tumors 30.7% were insignificant, 49.7% moderate and 19.6% advanced. The best model to predict preoperatively insignificant tumor was a free/total PSA of 0.15 or greater and favorable needle biopsy findings (less than 3 cores involved, none of the cores with greater than 50% tumor involvement and Gleason score less than 7). Using this model of the 18 tumors predicted to be insignificant 17 were insignificant for a positive predictive value of 94.4%. Of the 145 cases that were predicted to be significant 112 were correctly predicted for a negative predictive value of 77.2%. There was only 1 tumor predicted to be insignificant which was classified as moderate. No tumor predicted to be insignificant was advanced. CONCLUSIONS: In conjunction with needle biopsy findings, free/total PSA levels accurately predict insignificant tumor in stage T1c disease.

MY COMMENTS: This is a truly fascinating study. If you meet the qualifications you have "insignificant" tumor. I would think that if I qualified to have insignificant tumor I might not want to get treatment at this time. I would wait and get PSA's ever three to 6 months until something begin to show. Of course first I would want to rule out BPH and prostatitis as producing the PSA before I did anything.

They arrived at the definition of a "insignificant" tumor as being:

1. Nonpalpable

2. Stage T1c

3. Percent free PSA 15 or greater

4. Gleason less than 7

5. Less than three needle cores with none greater than 50% tumor.

If you meet these 5 specs, it certainly might be worth your time to think about not treating at the present time.

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Influence of Age

Influence of age and prostate-specific antigen on the chance of curable prostate cancer among men with Nonpalpable disease.

Carter HB, Epstein JI, Partin AW

Department of Urology, The Johns Hopkins University School of Medicine, The James Buchanan Brady Urological Institute, The Johns Hopkins Hospital, Baltimore, Maryland 21287-2101, USA.

OBJECTIVES: To evaluate the relation between age, prostate-specific antigen (PSA) level, and the probability of detecting curable prostate cancer. METHODS: A consecutive surgical series of radical prostatectomies was performed in 492 men with nonpalpable (Stage T1c) disease, who formed the study cohort (mean age 58 years). The cohort was systematically classified into three age groups ([1] 40 to 50 years [n = 69]; [2] 51 to 60 years [n = 227]; [3] 61 to 73 years [n = 196]) and five pretreatment PSA groups ([1] 2.5 to 4.0 ng/mL [n = 36]; [2] 4.1 to 6.0 ng/mL [n = 100]; [3] 6.1 to 8.0 ng/mL [n = 122]; [4] 8.1 to 10.0 ng/mL [n = 76]; [5] greater than 10.0 ng/mL [n = 135]). The percent probability of curable cancer was determined by logistic regression analysis. Curable cancer was defined as organ-confined tumor or a tumor with capsular penetration of low grade (Gleason score less than 7), with negative margins and no involvement of seminal vesicles or lymph nodes. RESULTS: A comparison within age groups and within PSA groups revealed that the probability of curable cancer was more closely associated with age than PSA level. Although the probability of curable cancer was closely related to PSA level across a wide range of PSA values (0.4 to 52 ng/mL), there was only minimal difference (2% to 4%) in the probability of curable cancer within the range of PSA values from 2.5 to 6.0 ng/mL for all ages. CONCLUSIONS: Age is a strong predictor of the probability of curable cancer. Thus, early detection efforts in younger men are more likely to lead to a decrease in prostate cancer mortality. These data suggest that the use of PSA thresholds below 4.0 ng/mL as an indicator of prostate cancer is unlikely to improve the probability of detecting curable cancer.

MY COMMENTS: Another interesting study to find out what percent of a curable cancer at what age based on PSA. Curable cancer (by RP) is defined as:

1. Organ-confined

2 Capsule penetration of cancer with a Gleason less than 7

3. Gleason less than 7

4. No involvement with seminal vesicles

5. No involvement with lymph nodes

6. Negative margins

7. Nonpalpable

8. Stage T1c

Now to put this in a form:

PSA............40-50 yrs.........51-60 yrs..........61-73 yrs

2.5-4.0..........89%...............83%...............78%

4.2-6.0..........87%...............81%...............74%

6.1-8.0..........84%...............78%...............71%

8.1-10.0.........83%...............75%...............67%

>10.1............73%...............57%...............49%

Now remember these were established with RP's with Stage T1c and nonpalpable. Note that the older you get the more "non-curable" you are at all levels of PSA. By using these figures my own curable rate would be 71%.

It would be most interesting to compare this with other treatments and studies using the same levels.

Another important part of this study is the showing of the PSA's from 2.5 to 4.0 as they reference to the "Age Adjusted PSA Tables" so often used. It is obvious that the detection of cancer at an earlier age may improve the probability of curing the disease. It shows that those older men, even with a PSA between 2.5 and 4.0 do not have a acceptable cure rate (at least to me) and that had no treatment been instituted because their PSA was below the "Age Adjusted" level they would lose another 4% possibility of cure. A reduction of 78% to 74%. But if we caught the same man at 40-50 we improve his possible cure rate by 11% - from 78% to 89% - seems significant to me.

Don

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Patient With Low PSA

This is an answer that Dr. Strum gave to a patient on p2p on March 28, 2000.

Patient states I am 49 years old and in good health. I have not been diagnosed with prostate cancer. Due to family cancer history, I have been getting PSA tests as part of my physical for several years. The results, all from the same lab, have trended upward from 0.2 to 0.4. Is this trend something to be concerned about, or are the numbers still low enough to be random variation? My urologist is not concerned due to the low numbers and my age.

Strum Replies: There are papers that show little concern for PC if the PSA is under 2. Another paper sites the threshold as 3. I would still want to see the effect of TIME on the PSA TREND. It is probable that we don't have enough tumor to detect PC at PSA levels that are very low. I would think that PERSISTENT increases consistent with a doubling time for PC should be the hallmark. I have not published on this as those below have. I therefore site you those papers.

Harris CH, Dalkin BL, Martin E, et al: Prospective longitudinal evaluation of men with initial prostate specific antigen levels of 4.0 ng./ml. or less [see comments]. J Urol 157:1740-3, 1997.

PURPOSE: We evaluated the 3-year longitudinal changes in serial serum prostate specific antigen (PSA) levels in men with an initial PSA of 4.0 ng./ml. or less and no suspicion of prostate cancer.

MATERIALS AND METHODS: A total of 760 men with an initial PSA of 4.0 ng./ml. or less plus a normal or suspicious digital rectal examination and a benign prostate biopsy was enrolled into an every 4-month PSA monitoring study.

RESULTS: Of the 559 men with an initial PSA of 2.0 ng./ml. or less only 3 (0.5%) had a persistently abnormal PSA for 3 years and 1 cancer (0.2%) was detected, and 48 men had a PSA velocity of 0.8 ng./ml. per year or more at year 1 but only 1 (2%) had a persistent rate of increase (2.4 ng./ml. per year) at 3 years. Of the 201 men with a PSA of 2.1 to 4.0 ng./ml. 85 had an abnormal PSA but only 37 (43%) met the criteria for biopsy. Only 8 of 23 biopsies (35%) revealed cancer. Of the 201 men 24 had a PSA velocity of 0.8 ng./ml. per year or more at year 1 but only 4 had persistence for 3 years. All 4 men had cancer but they were identified as at high risk by PSA criteria.

CONCLUSIONS: Men with a PSA of 2.0 ng./ml. or less are at low risk for an abnormal PSA or cancer within 3 years and annual monitoring may not be necessary. However, annual monitoring is clinically useful in men with an initial PSA of 2.1 to 4.0 ng./ml. Also, serial monitoring with interval testing in men whose PSA becomes greater than 4.0 ng./ml. is beneficial in identifying a high risk group requiring biopsy. Finally, PSA velocity did not add further to cancer detection in this population.

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Catalona WJ, Smith DS, Ornstein DK: Prostate cancer detection in men with serum PSA concentrations of 2.6 to 4.0 ng/mL and benign prostate examination. Enhancement of specificity with free PSA measurements [see comments]. JAMA 277:1452-5, 1997.

Comment in: SS JAMA SS 1997 May 14; 277(18):1475-6; Comment in: SS JAMA SS 1997 Sep 3; 278(9):699; discussion 700-1; Comment in: SS JAMA SS 1997 Sep 3; 278(9):699-700; discussion 700-1; Comment in: SS JAMA SS 1997 Sep 3; 278(9):700; discussion 700-1

OBJECTIVE: To determine the detection rate of prostate cancer in a screening population of men with prostate-specific antigen (PSA) concentrations of 2.6 to 4.0 ng/mL and a benign prostate examination, to assess the clinicopathological features of the cancers detected, and to assess the usefulness of measuring the ratio of free to total PSA to reduce the number of prostatic biopsies. DESIGN: A community-based study of serial screening for prostate cancer with serum PSA measurements and prostate examinations.

SETTING: University medical center.

SUBJECTS: A total of 914 consecutive screening volunteers aged 50 years or older with serum PSA levels of 2.6 to 4.0 ng/mL who had a benign prostate examination and no prior screening tests suspicious for prostate cancer, 332 (36%) of whom underwent biopsy of the prostate.

MAIN OUTCOME MEASURES: Cancer detection rate, clinical and pathological features of cancers detected, and specificity for cancer detection using measurements of percentage of free PSA.

RESULTS: Cancer was detected in 22% (73/332) of men who underwent biopsy. All cancers detected were clinically localized, and 81% (42/52) that were surgically staged were pathologically organ confined. Ten percent of the cancers were clinically low-volume and low-grade tumors, and 17% of those surgically staged were low-volume and low-grade or moderately low-grade tumors (possibly harmless). Using a percentage of free PSA cutoff of 27% or less as a criterion for performing prostatic biopsy would have detected 90% of cancers, avoided 18% of benign biopsies, and yielded a positive predictive value of 24% in men who underwent biopsy.

CONCLUSIONS: There is an appreciable rate of detectable prostate cancer in men with serum PSA levels of 2.6 to 4.0 ng/mL. The great majority of cancers detected have the features of medically important tumors. Free serum PSA measurements may reduce the number of additional biopsies required by the lower PSA cut off

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Labrie F, Candas B, Dupont A, et al: Screening decreases prostate cancer death: first analysis of the 1988 Quebec prospective randomized controlled trial. Prostate 38:83-91, 1999.

Department of Medicine, Laval University Medical Research Center (CHUL), Quebec, Canada. fernand.labrie@crchul.ulaval.ca

BACKGROUND: The 46,193 men aged 45 to 80 years registered in the electoral roll of Quebec City and its Metropolitan area were randomized in November 1988 between screening and no screening in a study aimed of assessing the impact of prostate cancer screening on cause-specific death.

METHODS: At first visit, screening included measurement of serum prostatic specific antigen (PSA) using 3.0 ng/ml as upper limit of normal and a digital rectal examination (DRE). Transrectal echography of the prostate (TRUS) was performed only if PSA and/or DRE was abnormal and biopsy was then done, only if PSA was above the predicted PSA value. At follow-up visits, PSA alone was used as prescreening. RESULTS: 137 deaths due to prostate cancer occurred between 1989 and 1996, inclusively, in the 38,056 unscreened men while only 5 deaths were observed among the 8,137 screened individuals. The prostate cancer death rates during the eight-year period were 48.7 and 15 per 100,000 man-years in the unscreened and screened groups, respectively, for a 3.25 odds ratio in favor of screening and early treatment (P < 0.01).

CONCLUSIONS: If PSA screening is started at the age of 50 years (or 45 years in the higher risk population), annual or biannual PSA alone is highly efficient to identify the men who are at high risk of having prostate cancer. Coupled with treatment of localized disease, this approach demonstrates, for the first time, that early diagnosis and treatment permits a dramatic decrease in deaths from prostate cancer. _____________________________________________________________________

Patient States: BTW, when these tests were done, I did not know that prior ejaculation could affect the results. I don't recall whether any such ejaculations occurred in the days before the tests.

Thank you for the incredible service that you provide.

PCD 3/00

current age 49, no PCa Dx, in very good health

2/00: DRE normal

1/00: PSA 0.4

8/98: PSA 0.3

8/96: PSA 0.2

Other urological symptoms:

- 1/00 discovered microscopic red blood cells in urine cytology negative, IVP negative, cystoscopy to be done 4/00

- rarely sleep through the night without getting up to urinate otherwise urination is not particularly frequent or urgent unless bladder is full

Family cancer history:

- Father died of leiomyosarcoma 1960, age 35

- Mother survived breast cancer 1958, current age 72>>

Strum Replies: There is a genetic link between PC and breast cancer. You should be on selenium 400 ug per day and Vitamin 8, 800 i.u. per day. Get a good quality Vit E and Selenium. I like Life Extension Foundation for an affordable brand of high quality vitamin. Check out www.lef.org Let us know about the cystoscopy. Good luck.

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