Prostate cancer never kills—metastatic prostate cancer does! Most men, at diagnosis, have bonescans that are “clear” or they have such a small PSA --less than 10-- that it would be very unlikely that they would have a positive bone scan. Their diagnosis typically does not include a bone scan.
     Approximately 15% of men are diagnosed with metastatic prostate cancer and about 20 to 30% of the men choosing localized treatment will eventually get metastatic disease (Small EJ, 2006). Whether one becomes metastatic is largely a function of the aggressivity of the cancer: very few of the men of the men with a Gleason score of 5, and increasing percentages with increasing Gleason scores.
     The metastatic cancer is typically step two in a two-step process. The first step is the recurrence of the cancer as indicated by an increase of the PSA after treatment. That increase can be so slow (the PSA doubling time is measured in years) that no action is required. But those men should keep track of their PSA diligently.
     How many men have recurrence? The percentage is a function of time: Even 15 years after treatment the cancer may return. This notion, making the word ‘cure’ rather evasive, follows from the recurrence (PSA > 0.2) percentages in the 2,091 men operated by Dr. Patrick Walsh (probably the best urologic surgeon in the USA before he recently retired): 16% had recurrence  after 5 years, 28% after 10 years, and 39% after 15 years (Han M, 2003). In the men operated by another eminent urologist, Dr. Horst Zincke of the Mayo Clinic, 36% and 47% of the 2,809 patients had recurrence (PSA >0.4) after 5 and 10 years, respectively (Roberts SG, 2001).
     According to the American Cancer Society one of six men will get prostate cancer but not all will choose local treatment: Some will opt for Watchful Waiting (Active Surveillance) and the men diagnosed with metastatic prostate cancer will receive hormonal treatment but the cancer will return eventually. Combining the two types of recurrence one can infer that about one of 16 men will have recurrence. As one of 34 men—according to the ACS— will die of prostate cancer, about 45% of men with recurrence will die of the disease. The numbers and percentages in this paragraph are rather tenuous and should be considered as ballpark figures.
     One of the few good things of prostate cancer is that it produces PSA which gives us a measuring tool no other cancer patient has. Keeping track of the PSA is of paramount importance. And even before the local procedure the PSA should have been tracked because with a PSA Doubling Time (PSADT) of more than 10 years recurrence after 5 years was only 1% in Dr. Zincke’s cohort, but if it was less than 0.5 year it was 36%. How many of our new members heading towards a RP or brachy knew their PSADT? Not one.
     If the PSA goes up after RP, the cancer has recurred. It is not as simple with brachytherapy. “Unlike surgical patients, PSA levels decrease over a prolonged period of time. Therefore, PSA assessment using an absolute level cannot be used immediately after treatment, but instead, the PSA level must be monitored for many years before an assessment can be made.” (Kuban DA, 2006). Also, 17% of patients in a cohort of 2,693 men experienced a PSA ‘”bounce” at a median time of 17 months after implantation. That is not a recurrence!
    The recurrence in the 2,693 men cohort was, after 10 years, about 38% if failure is defined as nadir (lowest PSA)+ 2. The speed with which the PSA goes up after failure of either RP or brachytherapy can be calculated with a calculator on our website pcngcincinnati.org. If the PSA goes up fast, that is, if the PSADT is short, one should truly pay attention. The obvious choice would then be to use what is the most aggressive treatment after recurrence:  hormonal therapy, now generally known as ADT (Androgen Deprivation Therapy). It can be done with orchiectomy, a LHRH injection, an antiandrogen (commonly Casodex 50 or 150 mg), or a combination.
     At my first PCNG meeting in 1996, I met Adrian Boie (1928-2005). He was the convener of our group at the time, and he was also one of the very first patients in the USA on Intermittent ADT. IADT has now been shown to be about as effective as continuous ADT (de Leval J, 2002), although continuous ADT may be better for those with a high Gleason score (Kaneko Y, 2006). Still, ADT will fail eventually.
     Beginning ADT or postponing ADT is thus a monumental decision. It is easy to make for those with a PSADT of a year or less, or for those with a PSADT of 10 years or more. But what if your PSA is doubling in a few years? Perhaps the PSADT can be slowed down, and the ADT can be postponed. And yes, there are some medications and even a few OTC (over-the-counter) food supplements which may just do that. They include Celebrex, for men without coronary problems (Smith MR, 2006), vitamin D (Woo TC, 2005), calcitriol (Beer TM, 2003), pomegranate juice (Pantuck AJ, 2006, see also our July newsletter) and MCP (Modified Citrus Pectin, Guess BW, 2003).
     However, only studies comparing a medicine with a placebo are valid as the PSADT can lengthen in both cohorts—only the Celebrex study had a placebo cohort. The necessity of this approach is illustrated by a recent study (Nelson JB, 2006) in which the PSADT lengthened 71% in the placebo group and 64% in the group that had the supposedly active medication (atrasentan aka Xinlay).
     If one medication works, are two not better? Or three? Dr. Charles Myers and other oncologists apparently think so, as they prescribe many of the medications listed above to all of their patients, irrespective of their PSADT, long or short.
     The only publication about the use of multiple medications after PSA begins to rise is based on a study by Dr. Fritz Schröder, the “Walsh” of The Netherlands (Schroder FH, 2005). In this study (placebo-controlled and “cross-over”: patients switch arms) the PSADT lengthened after taking a ‘multi-vitamin’ tablet with 21 ingredients including lycopene, soy, silymarin and selenium.
     This leads to the last percentage of this page: 30% of a Canadian cohort of 548 prostate cancer patients used over-the-counter (OTC) aka complimentary/alternative medicines (CAM). The most common are vitamin E, saw palmetto, and selenium.  Boon H, 2003 writes that “..men who had attended support groups were much more likely to use CAM. Men who had more advanced disease, and those who believed in the efficacy of CAM, but were not concerned about potential adverse effects of CAM, were also more likely to use CAM. CAM use was not related to education, income, or geographic location”.
     Unfortunately, ADT or IADT will eventually fail. The PSA begins to rise while the patient is on hormonal therapy. Now he has AIPC (Androgen Independent Prostate Cancer). This happened to me, 6.5 years after diagnosis, in the fall of 2003. My PSA rose from 0.48 to 0.56 and then to 0.68 while I was taking 150 mg of Casodex. But the next PSA value was 0.69, and if the beginning of AIPC is defined by three successive rises (Bubley GJ, 1999), October 2003 was not the time that my AIPC really began (I don’t consider 0.68 to 0.69 as a rise).
     The PSA was lowered by replacing the Casodex with Lupron and when that didn’t work, the addition of Casodex 150 mg. That kept the PSA at bay. This lasted until the fall of 2004: three successive rises of my PSA were measured, from a low 0.06 (the nadir) to 0.09, 0.16 and 0.47. My AIPC was now official (also according hrpca.org). And the last PSA value had been determined after I had stopped Casodex – there was thus no AAWR effect.
     Would I be eligible for a clinical trial? No. Bubley GJ, 1999 wrote: "We believe that a patient whose only evidence of progressive disease is an increasing PSA should have a value of at least 5 ng/mL before entering onto a clinical trial." My PSA (from 0.16 to 0.47 in one month) was doubling in 20 days, and assuming no change in the doubling time, it would have reached 5 in less than three months.
     I did not enter a clinical trial, but took various medications that eventually worked: My PSA went down! If I will be doing better than patients in a clinical trial, a possible explanation is that waiting until the PSA has reached 5 could be harmful.
     In addition, participation in a trial should not be considered before reading and carefully digesting the information on this web site: hrpca.org/clinicaltrialseditorial.htm.