A Medical Miranda For the PC Patient

In recent years numerous television shows have depicted our judicial system. All of us are now familiar with the principle of the Miranda.........."You have the right to remain silent, you have the right to an attorney....". Conceptually, the Miranda is frequently applied in medical practice but perhaps not enough. It would go something like this: "You have the right to know your diagnosis, --- You have the right to understand principles of evaluation and treatment, -- You have the right to be familiar with the pros and cons of available treatment options."

Too often patients are not read their medical Miranda (MM). We believe that patients with prostate cancer (PC) should have their MM. This MMPC or medical Miranda for prostate cancer patients should, at the very least, communicate the fundamental concepts involved in the evaluation and treatment of PC. We believe that your MMPC should involve your right to understand the following:

1. The concept of organ-confined disease: Is the PC likely to be confined to the prostate or is there a high risk that it is not? We know that systemic disease cannot be cured with local therapy, e.g. radical prostatectomy (RP), external beam radiation (RT), brachytherapy, or cryosurgery. Patients are entitled to know what group they belong to in regards to risk for systemic disease. Are they in a high, middle or low risk group? Using three pieces of information, the baseline PSA, Gleason's score and clinical stage, we can relay to the patient their degree of likelihood in having organ-confined disease, capsular penetration, seminal vesicle and lymph node involvement. We have termed these tables, The Partin Tables, from the work of Alan Partin MD of the Johns Hopkins Medical Center.1 We consider the Partin Tables to be the major prognostic paradigm for the 1990's. Perhaps the addition of RT- PCR or Complexed PSA may enhance the value of these tables or surpass them; this should be evaluated. For now, we consider a discussion of the findings of the Partin Tables an absolute must in the physician's initial or early discussion with the patient. In addition, in these days of concern regarding the cost of medical care, the Partin Tables will save millions of dollars in needless expense that involves inappropriate use of local therapy in the setting of overwhelming risk of systemic disease. Moreover the Tables are also able to indicate negligible risk for lymph node disease which might spare the patient the need for lymph node sampling and/or perhaps the need for pelvic CT or MRI. These studies would have a minimal chance of detecting such low-risk disease. Similarly, other reports have been published relating to risk-benefit and cost-savings in PC and relate to lymph node2 and bone involvement3. These should also not be ignored.

2. The concept of determination of extent of disease or stage This is intimately related to the article 1 above of the MMPC.

• How has the diagnosis of PC been evaluated?
   
• Has there been a comprehensive history and physical examination and basic laboratory tests that may have implications for my ability to receive treatment?
   
• Have the determinations of Gleason's score, clinical stage and PSA been made?
   
• Do I need a bone scan, endorectal MRI, pelvic MRI or pelvic CT?
   
• Is a determination of RT-PCR status for PSA relevant to treatment decisions in my case?
   
• We believe these are reasonable questions to ask your evaluating physician with the expectation of answers.

3. The concept of neoadjuvant hormone blockade (NHB). The use of upfront combination hormone blockade (CHB) with an anti- androgen (such as Casodex, Flutamide or Nilutamide) in combination with an LHRH agonist (such as Lupron or Zoladex), has been shown to decrease the frequency of positive surgical margins at the time of RP. This has been reported in at least 5 published studies, 4 of them randomized. Patients proceeding directly to RP without NHB have had approximately a 39% chance of positive surgical margins while those receiving NHB with CHB have had an average of ~ 13% positive surgical margins.

NHB Studies - % Surgical margins positive (number of patients)

Study Group	Year	w/o NHB	w/ 3 mos NHB
Labrie et al.4	1993	38.5% (65)	13% (77)
Fair et al.5	1993	33% (72)	10% (69)
Solomon et al.6	1993	35.3% (119)	11.5% (156)
Fair et al.7	1995	36% (92)	11% (92)
Gleave et al.8	1995		5% (36) a
Soloway et al.9	1995	47% (144)	17% (137)
Totals		39.2% (420) b	13.5% (462) c

(a) Not randomized - 8 mos CHB
(b) excluding Fair's 1st group
(c) excluding Gleave and Fair's 1st group

Thus, in 4 randomized studies from different institutions, the percentage of pathologically positive surgical margins (PPSM) in patients undergoing RP without NHB has been essentially identical. The benefit of 3 months of NHB with a reduction to approximately 13.5% from 39% of PPSM in all 4 studies attests to the validity of these findings. The reduction to 5% in one non-randomized study raises the issue of what is the optimal treatment time with CHB in a neoadjuvant setting.8 The use of the Partin Tables should also allow us to possibly bypass NHB in patients with favorable Gleason scores (2-4), low PSA readings (0-4) and clinical stages T1a to T2a. Predictions of organ- confined in such a setting is 85 to 100%. However, the prediction for capsular penetration of 22% in the T1c patients in the above group is still worrisome and would warrant a clinical trial to evaluate the need for NHB. The Partin Tables, if reviewed routinely for each patient being considered for local therapy with any current modality, would point out the risk for capsular penetration, seminal vesicle and lymph node involvement thus highlighting the need for NHB.

The long-term effects on survival with NHB are not available. The time in follow-up of patients receiving NHB has been too short for this determination. In Fair's study, the NHB subgroup with pathologically organ-confined disease (no patients with positive surgical margins , seminal vesicles, or lymph nodes) have shown the identical biochemical PSA relapse rate as those patients having RP only with pathologically organ-confined disease.7 Therefore 3 months of upfront CHB before RP appears to be having a biological effect on relapse. It appears to be not just "masking disease" as some opponents to CHB and NHB claim. In fact, in Walsh's book "The Prostate" neoadjuvant therapy is criticized with the statement: "hormone therapy is not a vacuum cleaner-it can't suck the cancer cells back into the prostate once they've escaped."10 If this really were the case then no neoadjuvant therapy for cancer should work. The data on converting non-resectable lung cancer to resectable with neoadjuvant chemotherapy or significantly improving survival with neoadjuvant therapy for head and neck cancer, breast cancer or soft- tissue sarcoma testifies to the validity of the concept of neoadjuvant therapy, be it hormonal or non-hormonal. The median follow-up time in the Fair et al study is 24 months. Further follow-up over the next 5 years will be critical in the assessment of the value of NHB on survival. For the time being it is reasonable to receive NHB.

4. The understanding of the pros and cons of different local and systemic therapies. Has your MD explained the pros and cons of treatment based on statistics from his practice or is he quoting the expertise of a physician(s) at a major medical center or another community practice? Too often we hear about physicians telling patients that incontinence after RP is only 1%, implying that that is their statistic, when in reality they have 40-50% incontinence rates. Make sure that your doctor is relating his experience, not that of others. Ask for the names and telephone numbers of the last 5 patients who had RP's and speak with those patients. Have the pros and cons of various treatment options been explained to you and do you have a copy of these in writing? Have you requested a copy of your consultation(s)- a consultation that either you and/or your insurance company have paid for? Our belief is that patients are to be the primary recipients of consultative reports; it is the patient's mind and body that are being affected. In our experience we have found the consultation reports to be wonderful teaching tools that brings the patient up to a level of understanding that is close to that of the doctor.

The MMPC is a concept that is of key importance to your welfare. You have the right to be informed of matters that relate to your health and welfare. You have the right to know.
PCRI 1996

REFERENCES

1. Partin AW, Yoo J, Carter HB, et al. The use of prostate specific antigen, clinical stage and Gleason score to predict pathological stage in men with localized prostate cancer. J Urology, 150:110-114, 1993.

2. Bluestein DL, Bostwick DG, Bergstralh EJ, et. al., Eliminating the need for bilateral pelvic lymphadenectomy in select patients with prostate cancer. J Urology, 151:1315-1320, 1994.

3. Chybowski F, Keller, J, Bergstralh E, et al. Predicting radionuclide bone scan findings in patients with newly diagnosed, untreated prostate cancer; prostate specific antigen is superior to all other clinical parameters. J Urol, 145:313-318, 1991.

4. Labrie F, Dupont A, Gomez J, et al. Downstaging of localized prostate cancer by neoadjuvant therapy with flutamide and lupron: the first controlled and randomized trial. Clin Invest Med 16:499-509, 1993.

5. Fair W, Aprikan A, Cohen D, et al. Use of neoadjuvant androgen deprivation therapy in clinically localized prostate cancer. Clin Invest Med 16:516-522, 1993.

6. Solomon M, McHugh T, Dorr R, et al. Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy. Clin Inves Med 16:532-538, 1993.

7. Fair W, Wang Y, Cohen D, et al. Neoadjuvant androgen deprivation therapy (ADT) in patients with clinically localized prostate cancer- effect on (+) margins and post-operative PSA. J Urol 153(4):313A, 1995.

8. Gleave M, Goldenberg L, Jones E, et al. Maximal biochemical and pathological downstaging requires 8 months of neoadjuvant hormonal therapy prior to radical prostatectomy. J Urol 153(4):392A, 1995.

9. Soloway M, Sharifi R, Wood D, et al. Randomized comparison of radical prostatectomy alone or preceded by androgen deprivation for cT2b prostate cancer. J Urol 153(4):391A, 1995.

10. Walsh P, Worthington J. The Prostate. Johns Hopkins University Press. p 88, 1995.

Prostate Cancer Research Institute (PCRI)
 

Material provided by PCRI is intended for educational purposes for discussion with your physician and should not be considered as medical advice. Information and opinions expressed on this website are not an endorsement by PCRI for any treatment, product or service.