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Advanced Prostate Cancer
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Advanced Prostate Cancer

I had removel (removal) of my prostate 9 years ago.  After 4 1/2 years I started to have a rising PSA again.  I had 52 treatments of radiation.  (bad stuff). My PSA started to rise again.  Dr. put me on Lupron and Casedex.  PSA continues to rise.  Took me off of casedex.  I am still getting Lupron shots.  PSA is now 16.7.  What happens next?  Does it go to my bones?  What systems am I looking for?  Will Chemo be in the picture soon? When?  What kind of chemo?  everyday?  once a month?   Please try and answer some of my questions
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Thank you for your question. Chris is right when it comes to advanced prostate cancer. There is no permanent cure but you can beat the odds.

To answer your question, you still have PSA-only recurrence. Such increases are not accompanied by symptoms, signs, or imaging evidence of locally recurrent or metastatic disease.  In one study, men with a biochemical recurrence after RP for localized disease had a 10-year survival rate that was similar to men without detectable PSA during follow-up (88 and 93 percent, respectively) [1]. In a second report, only 34 percent of men who had a biochemical recurrence (defined as PSA greater than 0.2 ng/mL) developed metastatic disease within eight years [2]. The prognosis of men with prostate cancer following a PSA relapse is diverse, and biochemical failure does not necessarily predict death [1,2,3]. The variability in prognosis in different series ranges from estimates in the four to five year range to as much as fifteen years or more. Several parameters (eg, PSA-doubling time, Gleason score, PSA response to salvage Androgen Deprivation Therapy) have been studied to distinguish men who are likely to develop "clinically significant" biochemical recurrence following either radical prostatectomy or Radiation Therapy from those who have more indolent disease [4-13]. It seems your PSA rise has been resistant to both RT and ADT.

There are chances of metastases and for men with disseminated disease, bone metastases are the most common site of involvement. The objective of therapy is control of disease while maintaining quality of life. The initial approach is generally androgen deprivation therapy (ADT). Patients who progress on ADT in the face of castrate levels of testosterone are considered to have "castrate-resistant" prostate cancer. These patients have also been referred to as having hormone-refractory prostate cancer (HRPC) or androgen-independent prostate cancer (AIPC). Nearly all men with metastatic prostate cancer eventually develop progressive disease after treatment with ADT. These men may still have clinically important responses to other hormonal interventions. Patients who have progressed on ADT and are not responsive to secondary hormonal therapies may benefit from chemotherapy. Between 1984 and 1991, 30 to 40 percent of men presented with advanced disease [14]; at present, only 5 percent have distant metastases at the time of diagnosis [15].  

Chemotherapy may provide clinical benefit for patients no longer responding to hormonal therapies. Early clinical trials suggested that chemotherapy was ineffective in castrate-resistant prostate cancer. Objective response rates were 10 to 20 percent, and median survival did not exceed 12 months. However, newer regimens, based upon docetaxel and mitoxantrone, have resulted in objective responses and clinical benefit. In the 1990s, two randomized trials showed that mitoxantrone plus a corticosteroid improved palliative endpoints, but not survival, compared to a corticosteroid alone. Subsequently, the TAX-327 trial demonstrated that docetaxel given every three weeks plus daily prednisone significantly prolonged survival compared to mitoxantrone plus prednisone (median survival 19.2 versus 16.3 months and three-year survival rates 18.6 versus 13.5 percent) [16,17]. A similar survival benefit for docetaxel-based chemotherapy was seen in a second trial that compared docetaxel plus estramustine with mitoxantrone plus hydrocortisone. However, the docetaxel plus prednisone combination is preferred because of the risk of thromboembolic events associated with estramustine.

The Cancer Care Ontario Practice guidelines, which were endorsed by the American Society of Clinical Oncology (ASCO), recommend docetaxel (75 mg/m2) every three weeks plus prednisone (5 mg twice a day) for chemotherapy in men with castrate-resistant prostate cancer [18,19]. The guidelines recommend the continuation of gonadal androgen suppression but not antiandrogens during chemotherapy. Estramustine-based combinations are not recommended because of the higher incidence of complications. Docetaxel-containing chemotherapy has not been compared with second-line hormone therapy in a randomized trial in men progressing after ADT. However, the toxicity profile of sequential hormonal maneuvers tends to be more favorable than that of chemotherapy, and most men are offered a trial of second-line hormonal therapy before proceeding to systemic chemotherapy. The best treatment for men who fail docetaxel-based therapy is unclear. In this setting, both ixabepilone and the combination of mitoxantrone plus prednisone appear to have activity in some men.

You should also participate in clinical trials whenever possible.

I hope it answers some of your questions. There are several treatment options available for advanced prostate cancer and need to be discussed in detail with your doctor. Please look up the references below.

Sincerely,

Ash Tewari, MD

http://www.cornellroboticprostate.org

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Hi Slippery,

I am sorry to hear about your condition and am also a PCa patient (Gleason 9, T3). Like you, I had a Radical Prostatectomy.   My PSA test 90 days after surgery was already 0.7, AKA biochemical failure.  In short, the surgery was too late.  

As a result I have researched and studied prostate cancer conditions, treatments and prognosis literature until the wee hours of the morning trying to get a clear picture of what to do and what to expect.

As you may know there is no permanent cure for advanced prostate cancer (yet). Radiation will slow down progression as will hormone therapy and chemo but none will cure advanced prostate cancer.

To maximize my chances I have had hormone therapy (Lupron & Casodex for 6 mos)  combined with radiation therapy (38x IMRT sessions at 180 units/day) and will start chemo therapy (75 mg Taxotare, 8x sessions, 3 weeks apart) in about 2 weeks.

From your brief description of treatments and results it sounds like you may have something known as "hormone refractory prostate cancer".  It's a fancy way of saying that hormone therapy has done what it can and the cancer continues to develop.  
I can't predict what your treatment course will be but I suspect your treatment may move to Chemo next.  There are several drugs approved for use now and there are a number of clinical trials under way as well.  I joined a clinical trial and am happy I did.  It offers some possibility of slowing progression and will eventually help develop better treatment protocols.

Any way, the progression of the cancer past the prostate is called metastatic, which most often goes to the bone.

Metastatic prostate cancer is the beginning of the end game with prostate cancer and may be treated with chemotherapy to slow things down and/or radiation (to reduce the size of the tumor(s), and/or diminish any pain (palliative therapy) they cause).

It's not a great future we have but then there are many folks who have beaten the odds and are alive and well years after biochemical failure following prostatectomy and years after developing hormone refractory PCa.

I hope you do well and will join the ranks of patients who beat the traditional prognosis and timelines.  

In the meantime I hope to live long enough to die with prostate cancer rather than die from prostate cancer.

Best of luck to you

Chris




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242579_tn?1252114771
References:

1. Jhaveri, FM, Zippe, CD, Klein, EA, Kupelian, PA. Biochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results. Urology 1999; 54:884.

2. Pound, CR, Partin, AW, Eisenberger, MA, et al. Natural history of progression after PSA elevation following radical prostatectomy. JAMA 1999; 281:1591.

3. Freedland, SJ, Humphreys, EB, Mangold, LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 2005; 294:433.

4. D'Amico, AV, Moul, J, Carroll, PR, et al. Cancer-specific mortality after surgery or radiation for patients with clinically localized prostate cancer managed during the prostate-specific antigen era. J Clin Oncol 2003; 21:2163.

5. Kupelian, PA, Buchsbaum, JC, Patel, C, et al. Impact of biochemical failure on overall survival after radiation therapy for localized prostate cancer in the PSA era. Int J Radiat Oncol Biol Phys 2002; 52:704.

6. Taylor, JM, Yu, M, Sandler, HM. Individualized predictions of disease progression following radiation therapy for prostate cancer. J Clin Oncol 2005; 23:816.

7. Roach M, 3rd, Hanks, G, Thames, H Jr, et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys 2006; 65:965.

8. Kupelian, PA, Mahadevan, A, Reddy, CA, et al. Use of different definitions of biochemical failure after external beam radiotherapy changes conclusions about relative treatment efficacy for localized prostate cancer. Urology 2006; 68:593.

9. Freedland, SJ, Humphreys, EB, Mangold, LA, et al. Risk of prostate cancer-specific mortality following biochemical recurrence after radical prostatectomy. JAMA 2005; 294:433.

10. Horwitz, EM, Vicini, FA, Ziaja, EL, et al. The correlation between the ASTRO Consensus Panel definition of biochemical failure and clinical outcome for patients with prostate cancer treated with external beam irradiation. American Society of Therapeutic Radiology and Oncology. Int J Radiat Oncol Biol Phys 1998; 41:267.

11. Horwitz, EM, Thames, HD, Kuban, DA, et al. Definitions of biochemical failure that best predict clinical failure in patients with prostate cancer treated with external beam radiation alone: a multi-institutional pooled analysis. J Urol 2005; 173:797.

12. D'Amico, AV, McLeod, DG, Carroll, PR, et al. Time to an undetectable prostate-specific antigen (PSA) after androgen suppression therapy for postoperative or postradiation PSA recurrence and prostate cancer-specific mortality. Cancer 2007; 109:1290.

13. Freedland, SJ, Humphreys, EB, Mangold, LA, et al. Death in patients with recurrent prostate cancer after radical prostatectomy: prostate-specific antigen doubling time subgroups and their associated contributions to all-cause mortality. J Clin Oncol 2007; 25:1765.

14. SEER Cancer Statistics Review, 1973-1999. Ries, LA, Eisner, MP, Kosary, CL, et al, eds. National Cancer Institute. Bethesda, MD, 2002. http://seer.cancer.gov/csr/1973_1999/2002.

15. Jemal, A, Siegel, R, Ward, E, et al. Cancer statistics, 2008. CA Cancer J Clin 2008; 58:71.

16. Tannock, IF, de Wit, R, Berry, WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004; 351:1502.

17. Berthold, DR, Pond, GR, Soban, F, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol 2008; 26:242.

18. Winquist, E, Waldron, T, Berry, S, et al. Nonhormonal systemic therapy in men with hormone-refractory prostate cancer: A Clinical Practice Guideline, 2005. (Available online at www.cancercare.on.ca/pdf/pebc3-15s.pdf, accessed on January 23, 2008).

19. Basch, EM, Somerfield, MR, Beer, TM, et al. American Society of Clinical Oncology endorsement of the Cancer Care Ontario Practice Guideline on nonhormonal therapy for men with metastatic hormone-refractory (castration-resistant) prostate cancer. J Clin Oncol 2007; 25:5313.

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