Recurring Prostate Cancer After Failed Surgery and Radiation Treatment

Dear Susan & Don

I am deeply sorry to hear the answer you received from Loma Linda, but at least you tried. In your personal thread, TC-Las Vegas just posted a suggestion for you to consider. The real question is whether or not you can find any treatment center that would offer radiation to treat Don's condition. Keep in mind that IMRT x-ray radiation is readily available throughout the U.S. unlike proton radiation. It is true that radiation treatment (i.e., x-ray) was not very sophisticated years ago and the side effects were horrible in many cases. This is no longer true because of the advances made in x-ray radiation in recent years (i.e., IMRT and IGRT). Didyou ever ask an expert doctor if the cancer in the distant nodes could be treated by surgery? I am still hoping and praying that you will touch upon some solution to wiping out Don's remaining cancer. Don't give up hope. God Bless!

Dave

I have not read this book nor am I promoting sales of this book. I came across this article and thought it appropriate to post it for anyone who wants to investigate the findings in the book. I believe that Dr. Myers is considered reputable within the prostate cancer medical field. I have no idea if his proclaimed successful treatment is applicable to others.

http://www.cancercompass.com/cancer-news/1,12464,00.htm?c=1004:5:1:2

Prostate Cancer Book Delivers Hope

April 11, 2007

CHARLOTTESVILLE, Va. -- Rivanna Health Publications recently announced the publication of prostate cancer specialist and survivor, Dr. Charles "Snuffy" Myers's newest weapon in the fight against prostate cancer: The book "Beating Prostate Cancer: Hormonal Therapy and Diet" is a crucial resource for effecting remission with androgen blockade alone or in tandem with radiation or surgery.

Utilizing a simple golf metaphor to outline the twists and turns of diagnosis and treatment, the book addresses metastatic patients, the newly diagnosed, and healthcare professionals alike. Topics include: Hormonal Therapy Regimens, Diet/Lifestyle, Radiation, Surgery, and many others.

"Prostate cancer is like golf," notes Myers. "You need to play it as it lies. Because the disease is variable, each treatment solution requires a unique strategy. Yet I was astonished that I couldn't find a single resource that outlined hormonal therapy's benefits when I've seen great results both in my practice and personally. Cancer is no longer a death sentence, and the book delivers the hope men need to survive and thrive."

"Myers is clearly one of the leading doctors in the field," says Jim Waldenfels, well-known prostate cancer activist and survivor. "He's the best at communicating sound information that is understandable."

While "Beating Prostate Cancer" offers critical information from a leading international expert, what makes this book truly special is that Myers is also a survivor with a now undetectable PSA. Diagnosed at fifty-five, Myers is living proof of his program's success, and uses his own road to recovery to give men perspective from both sides of the examination table.

"It reads like a novel. No clunky science-speak," says survivor Michael Forrest, and Us TOO Member, Roy Bradbrooke adds "Myers's program works. His dietary recommendations saved my life."

Beating Prostate Cancer is available exclusively from the publisher by calling 800-305-2432 or by logging on to http://www.prostateforum.com.

Medical oncologist, scientist, and nutrition expert, Dr. Charles "Snuffy" Myers was a key player in creating AZT, Suranim, and Phenylacetate while working at NIH. With over 250 research papers published, Myers is one of the leading developers of today's prostate cancer canon. Former Cancer Director at the University of Virginia, Myers opened the American Institute for Diseases of the Prostate in 2001 to provide men with the comprehensive care that saved his life.

SOURCE Rivanna Health Publications

Copyright (C) 2007 PR Newswire. All Rights Reserved

Hi ~ egilman,    Welcome!!   In New Friendship ~ Lee & Buddy  We hope this link helps you!! Scroll down to the 3rd posting when you get there for some quick links.. (Direct Link ~ just click on the title below and a new window will open!   Reminder … click on the REFRESH icon once you get there) Helpful Hints ~ & ~ Direct Links to Important Topic Threads ~ Hope this helps you!! :)    

I found this to be a very informative discussion.
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1477547

Treatment Options after Failure of Radiation Therapy—A Review

Abstract

Radioresistant or recurrent prostate cancer represents a serious health risk for approximately 20%–30% of patients treated with primary radiation therapy for clinically localized prostate cancer. The majority of patients exhibit large volume and poorly differentiated disease at the time of diagnosis, which limits the ability of salvage therapy to eradicate the cancer. Early detection with serum PSA monitoring and prostate needle biopsy following primary radiation therapy may identify residual adenocarcinoma at an earlier stage and increase the likelihood of successful salvage therapy. Radical prostatectomy, prostate cryoablation, and brachytherapy comprise the options for salvage treatment available for radiorecurrent prostate cancer. The goal of disease eradication must be balanced against the potential for serious treatment-related side effects. As a result, many patients receive noncurative therapy with androgen ablation despite the real risk of disease progression and mortality.
Key words: Radiorecurrent prostate cancer, Early detection, Salvage therapy,

Despite the absence of a clearly articulated national policy for screening for prostate cancer, the widespread adoption of early detection approaches in men has resulted in the diagnosis of approximately 200,000 new cases each year. Additionally, the application of serum prostate-specific antigen (PSA) and digital rectal examination (DRE) has increased the likelihood that these cancers will be clinically nonpalpable, small in volume, and pathologically confined to the prostate. Therefore the majority of these individuals will appear initially to have localized disease and, following a complex decision process, will undergo an attempt at curative therapy. It can be argued that these patients then diverge into two distinct populations. The larger population will be cured of the prostate cancer by their chosen primary treatment and, with the possible exception of therapy for treatment-related side effects, require only routine surveillance. The second group will experience persistence or recurrence of their disease and face the need for additional therapy and possible disease-related mortality.

The stratification of an individual patient into one or the other of these two group is difficult for any local therapy but particularly challenging for patients treated with radiation therapy. Recent technological advances have increased the attractiveness of both external beam radiation therapy and brachytherapy as primary therapy for localized prostate cancer to such an extent that approximately 50,000 patients are treated with these modalities each year.1 Although these treatments are designed to ablate all glandular elements of the prostate, the obliterative process can take many months and may ultimately be incomplete. Therefore the definitive assignment of patients to one of the two groups following treatment is often difficult, even when based on DRE, serum PSA levels, and prostate needle biopsy. The remainder of this review will examine the arguments for careful screening of patients treated with radiation therapy for localized prostate cancer, recommendations for follow-up testing, and salvage therapy options once persistent disease has been identified.

Detection of Persistent Prostate Cancer Following Radiation Therapy
The variable and often protracted natural history of untreated prostate cancer has complicated the development of a cogent policy for screening for early-stage cancer. In fact, patients with well-differentiated or moderately well-differentiated prostate cancer exhibit an 87% 10-year disease-specific survival rate when managed with noncurative therapy alone.2 It is therefore difficult to determine the value of early detection efforts and treatment for these patients. This expectation of prolonged survival for a man with untreated prostate cancer may bias physicians toward a less intensive diagnostic approach to all forms of clinically localized prostate cancer. However, persistent prostate cancer following radiation therapy represents a more aggressive disease state that results in cancer-related death in at least 27% of patients within 5 years of exhibiting a rising PSA.3 Furthermore, recurrent neoplasms demonstrate a 24% increase in Gleason 8–10 cancers and a 31% increase in aneuploid tumors when compared to pretreatment characteristics.4 Finally, these cancers are often large in volume and are associated with extracapsular extension and positive margins in 40%–60% and lymph node metastases in 14%–34% cases.5 Clearly, recurrent prostate adenocarcinoma following radiation therapy poses a serious health risk to men. Conceptually, the limited population of men at risk is readily identifiable, and hence an active early detection approach could be expected to reduce the stage of presentation and reduce mortality.

Both benign and malignant prostatic glandular epithelia are injured by radiation therapy, which ultimately results in clearance of damaged cells through the process of programmed cell death. This process may take many months following the completion of therapy, and so diagnostic tests, including serum PSA and prostate needle biopsy, must be interpreted with caution. In particular, serum PSA levels decline slowly over 6–18 months after radiation, with a nadir value often reached as late as 33 months.6 PSA levels can actually rise following brachytherapy and may fluctuate during surveillance due to benign prostatic disease.7,8 The American Society for Therapeutic Radiology and Oncology consensus panel attempted to deal with these confounding findings by defining biochemical failure after radiation therapy as three successive increases in PSA after reaching a PSA nadir.9 Although this definition is now the standard in the radiation therapy literature, it may underestimate the ultimate biochemical failure rates and delay the diagnosis of a persistent cancer. A potentially more clinically useful parameter would be a PSA nadir below 0.5 ng/mL. Approximately 90% of patients who achieve this PSA nadir within 2 years remain free of recurrent disease.10 Additionally, any rise in PSA levels following the nadir is associated with a high risk of recurrent disease. It is important to note that the rate of disease progression following salvage radical prostatectomy is lowest when the disease is treated at a serum PSA below 10 ng/mL. In one salvage prostatectomy series, cancer-specific 5-year survival rate was 100% for patients with PSA below 4.0 ng/mL.11 Therefore earlier identification of radioresistant prostate cancer may result in more efficacious salvage therapy. Information regarding PSA-progression-free survival following radiation therapy is provided in Table 1.

Table 1--PSA-Progression-Free Survival After Radiation
Once a meaningful elevation in the serum PSA level has been identified, a transrectal ultrasound and prostate needle biopsy are warranted. Again, the biopsy findings must be interpreted with an understanding of the histologic effects of radiation on prostate tissue. Severe radiation effects with both nuclear and cytoplasmic alterations are seen in many prostatic biopsies and may confound the diagnosis of residual cancer.12 It is possible that this explains the finding that 67% of patients with adenocarcinoma on a biopsy at 12 months following radiation will convert to negative histology by 16–29 months.13 Given the delayed clearance of neoplastic cells after a course of external beam radiation or brachytherapy, it appears wise to perform any initial prostate biopsy at 12–18 months posttreatment. This could be coincident with a PSA nadir above 0.5 ng/mL or any rise in the serum PSA level. The incidence of positive biopsy results after primary radiation therapy varies widely in the literature but appears to be higher for external beam radiation than for brachytherapy.14 A selective summary of prostate biopsy results after radiation is presented in Table 2.

Table 2--Results of Prostate Biopsy After Radiation

Salvage Therapy Options

Salvage Radical Prostatectomy
Salvage radical prostatectomy is the most commonly performed curative treatment for clinically localized prostate cancer after radiation therapy. This procedure is capable of eradicating the local lesion and providing long-term disease-specific survival. Several clinical series have reported actuarial cancer-specific survival rates of 64%–88% at 5 years with PSA-progression-free survival rate of 83%.5,15 Despite the potential for successful extirpation of the cancer, the surgical procedure is complicated by the tissue effects of radiation and is associated with significant side effects. Radiation results in vascular occlusion with resulting tissue hypoxia, while alterations in basement membrane proteins lead to increased fibrosis. Hence anatomical planes between pelvic organs are often obliterated, with a poorly vascularized bladder and urethra available for surgical reconstruction. As a result, surgical extirpation is associated with a variety of treatment-related toxicities, such as universal erectile dysfunction, which can diminish enthusiasm for this treatment modality. Several of the more common treatment-related side effects of salvage radical prostatectomy are listed in Table 3.

Table 3--Salvage Therapy-Related Adverse Events

Salvage Prostate Cryoablation
The expectation of pelvic vascular injury and radiation-induced fibrosis has stimulated interest in salvage treatments that may ablate the prostate in situ. Percutaneous prostatic cryoablation represents such an approach. An early experience reported by Bales and coworkers in 1995 in 23 patients treated with cryoablation demonstrated an 86% negative biopsy rate at 3 months following the procedure but a 100% rate of adverse events.17 Subsequently, several other groups have detailed their clinical experience with salvage cryoablation, demonstrating reasonable rates of disease control with improved toxicity. The incidence of negative postprocedure prostate biopsy ranges from 63% to 97%, and 60% to 96% achieve an undetectable PSA nadir.18,19 Most recently, the application of an argon gas-based cryoablation unit coupled with temperature monitoring of the freezing process has reduced the rate of urinary incontinence and rectal injury to 9% and 0%, respectively.17 One common adverse event, sloughing of necrotic urethral tissue with secondary urinary obstruction, has also been reduced in incidence from 10%–15% to as low as 0% with alterations in technique and application of a urethral warming catheter. Therefore it appears that salvage cryoablation of the prostate is a viable and potentially attractive treatment for radioresistant prostate cancer.

Salvage Brachytherapy
Clinical experience with radiation therapy for localized prostate cancer has suggested that cancer eradication is improved at higher doses of radiation. Therefore proponents of external beam radiation therapy as primary treatment are now advocating doses greater than 80 Gy. Historically, patients have received from 60 to 70 Gy, which may be an inadequate dose. This has led to the application of transperineal permanent brachytherapy for patients with recurrent clinically localized prostate cancer. In one series, 49 patients underwent permanent implantation for an additional dose of 120–126 Gy with a median follow-up of 23 months. A total of 28 patients exhibited clinical progression of disease, with an actuarial biochemical disease-free survival rate of 48%.20 Treatment-related side effects included urinary incontinence in 6%–24%, persistent penile discomfort, and rectal bleeding.21 These preliminary reports suggest that salvage brachytherapy may successfully control the local disease within the prostate in some patients, despite the fact that the cancer failed to respond to the initial external beam treatments. The ultimate toxicity of this approach remains to be established with patient-focused questionnaires.

Salvage Androgen Ablation Therapy
Hormonal manipulation is likely to be the therapy most commonly administered to patients with recurrent prostate cancer and yet it has been the least well studied to date. A total of 54% of urologists and radiation oncologists in one study recommended androgen ablation or observation with delayed androgen ablation for patients with recurrent prostate cancer.22 Certainly, androgen ablation is not a curative intervention, and therefore the optimal timing of its application is uncertain. The cancer-specific survival after androgen ablation administered upon identification of local-only recurrence in one series of 72 patients was 70 (external beam) and 84 (brachytherapy) months.23 Although this relatively short survival may be a reflection of the advanced stage of disease of these patients or the intrinsic response rate of prostate cancer to hormonal therapy, the more morbid attempts at salvage therapy, such as radical prostatectomy, cryoablation, and brachytherapy, should demonstrate improved survival beyond that of androgen ablation in order to be reasonably administered to patients with recurrent prostate cancer.

Conclusion
Radiorecurrent or resistant prostate cancer is an aggressive form of localized prostate cancer that poses significant health risks to the men with this disease. An active program of surveillance and early detection with serum PSA and prostate biopsy is warranted for patients treated with radiation as primary therapy. The best outcomes from salvage treatments have been accomplished in patients identified upon biochemical failure at a PSA level below 4.0 ng/mL. A routine prostate biopsy at 12–24 months after radiation therapy or in patients with a PSA nadir above 0.5 ng/mL is likely to identify residual cancer as early as possible. Although the exact natural history of this residual disease is unclear, it remains highly likely that these patients will experience a clinically relevant progression of their disease if left untreated. Salvage radical prostatectomy represents the current best curative therapy, while cryoablation and brachytherapy are attractive alternatives. It is important that these salvage local therapies minimize treatment-related side effects while demonstrating a disease-specific survival rate greater than androgen ablation.

Main Points·
Persistent prostate cancer following radiation therapy results in cancer-related death in at least 27% of patients within 5 years of exhibiting a rising serum prostate-specific antigen (PSA) level.·

Approximately 90% of patients who achieve a PSA nadir below 0.5 ng/mL within 2 years remain free of recurrent disease.·

Disease progression following salvage radical prostatectomy is lowest when the disease is treated at a serum PSA below 10 ng/mL.·

Severe radiation effects with both nuclear and cytoplasmic alterations are seen in many prostatic biopsies and may confound the diagnosis of residual cancer; 67% of patients with adenocarcinoma on a biopsy at 12 months following radiation will convert to negative histology by 16–29 months.·

Incidence of positive biopsy results after primary radiation therapy appears to be higher for external beam radiation than for brachytherapy.·

Salvage radical prostatectomy is capable of eradicating the local lesion and providing long-term disease-specific survival, but it is complicated by the tissue effects of radiation and is associated with significant side effects, such as universal erectile dysfunction.·

An argon gas-based cryoablation unit coupled with temperature monitoring of the freezing process has reduced the rate of urinary incontinence and rectal injury to 9% and 0%, respectively, in percutaneous prostatic cryoablation.·

Salvage brachytherapy may successfully control local disease within the prostate in some patients.

http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1477547

eglman,

My first post op PSA was done at six weeks after surgery and it was undetectable. My next one will be done at six months post op in June.

Tamu

I found this recent study from Germany very interesting--it may contain useful information for those patients who have had prostate surgery (Stage T2 and T3) only to find that they have positive margins and/or elevated PSA readings after surgery or sometime later. The summary study information below is somewhat limited and you may have to refer to the detail study for more definitive information. 

Studies From University Hospital Further Understanding Of Prostate Cancer Therapy

May 9, 2007

Research findings, "Adjuvant radiotherapy after radical prostatectomy: indications, results and side effects," are discussed in a new report. "Within 5 years following radical prostatectomy, between 15 and 60% of patients with pT3 prostate carcinomas show an increasing prostate-specific antigen (PSA) level as a sign of local and/or systemic tumor progression. Apart from a large number of retrospective investigations, available results are present only from three randomized studies which have either been completely published or are only in abstract form," scientists in Ulm, Germany report.

"For pT3 prostate carcinomas the data from the three randomized studies agree, showing an around 20% reduced biochemical progression rate after 4-5 years. With these data the results of numerous retrospective studies have been confirmed. The majority of the authors use total doses of 60 Gy with single doses of 2 Gy. From one randomized study an increased local control rate is proposed as the basis for the extended freedom from biochemical progression. The rate of acute and late side effects after three-dimensional radiotherapy with 60 Gy is very small and the rate of severe side effects is below 2%. The data for pT2 prostate carcinomas with positive margins are worse. Here controversy exists, and further investigations are required. In principle, however, adjuvant radiotherapy seems reasonable also for pT2 carcinomas with positive margins (determined by bNED -no biochemical evidence of disease). The effectiveness of adjuvant radiotherapy for patients with pT3 tumors and positive margins with and without detectable PSA levels is discussed. A survival advantage has not been demonstrated to date. For patients with positive margins in organ-limited prostate carcinomas (pT2 R1) randomized studies are recommended. It is unclear whether adjuvant radiotherapy is superior to radiotherapy for PSA levels increasing from the undetectable range after radical prostatectomy," wrote D. Bottke and colleagues, University Hospital.

The researchers concluded: "To answer this question randomized studies are needed."

Bottke and colleagues published their study in Urologia Internationalis (Adjuvant radiotherapy after radical prostatectomy: indications, results and side effects. Urologia Internationalis, 2007;78(3):193-7).

For more information, contact D. Bottke, University Hospital Ulm, Dept. of Radiotherapy and Radiation Oncology, Ulm, Germany.

Publisher contact information for the journal Urologia Internationalis is: Karger, Allschwilerstrasse 10, CH-4009 Basel, Switzerland.

http://www.cancercompass.com/cancer-news/1,12589,00.htm?c=1004:5:1:2

Chemotherapy Combination Shows Benefits For Prostate Cancer Patients

June 3, 2007

CHICAGO -- Combining an oral dose of Xeloda with a weekly intravenous dose of Docetaxel in patients with metastatic prostate cancer improves patient remission and survival outcomes, according to a phase II clinical trial recently completed at the Barbara Ann Karmanos Cancer Institute in Detroit, MI.

In research presented today at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL, Karmanos physicians found that the combination of the two chemotherapies worked better than Docetaxel alone, which is the current standard of care for metastatic prostate cancer.

"This combination appears extremely effective. We had wheelchair bound patients return to their regular lives. Patients feel so much better and their overall quality of life improves dramatically," said Ulka Vaishampayan, M.D., chair of the genitourinary multidisciplinary team at Karmanos.

On average, patients who undergo the current standard of care see a 45 percent decline in their prostate-specific antigen (PSA) levels. With the combination chemotherapy trial, 73 percent of patients saw at least a 50 percent decrease and nearly a third had a 90 percent decrease.

"We used this combination even in ill patients with severe bone pain and weight loss and saw promising results. This combination is tolerated well, even in elderly patients," stated Dr. Vaishampayan.

Metastatic prostate cancer spreads to the bones more often than other types of metastatic cancers, causing significant pain for patients. Karmanos physicians will continue to follow the 30 patients who enrolled in and completed the trial and work to find other novel agents to combine with Docetaxel.

The lead author for this abstract is Shanthi Marur, M.D., a Karmanos fellow mentored by Dr. Vaishampayan. Dr. Marur received an ASCO merit award for this abstract. ASCO merit awards are given annually to recognize outstanding abstracts submitted for consideration for presentation at an ASCO scientific meeting. The awards are given to oncology fellows in training who are first authors on selected abstracts.

ASCO is the world's leading professional organization representing physicians who treat people with cancer. ASCO's members set the standard for patient care worldwide and lead the way in carrying out clinical research aimed at improving the prevention, diagnosis, and treatment of cancer. ASCO's efforts are also directed toward advocating for policies that provide access to high-quality care for all patients with cancer and at supporting the increased funding for clinical and translational research.

Based in midtown Detroit, the Barbara Ann Karmanos Cancer Institute is committed to a future free of cancer.

http://www.cancercompass.com/cancer-news/1,12733,00.htm?c=1004:5:1:2

Dear Susan

I try to pass along new information that may be helpful to those who have to battle a more advanced stage of PCa. I am happy to hear that Don's PCa appears under control at the present time as evidenced by his low PSA. So much PCa research is going on these days--we can only hope and pray that some new miracle drug or other treatment will soon come along to better help those with an advanced stage of PCa. God Bless!

Dave

Hi Fred,
First you have my caring and prayers. I too am a Gleason 7 (4+3) and have had adjuvant RT & HT after surgery. I have fared well with the treatments to date. While I have been proactive about treatment, I went undetectable after surgery, I live in knowledge that I will likely recur because of the high pre-operative PSA (19.8) and 4 positive margins. It seems that I am doing quite well with a shadow that has my doctors saying that I needed these adjuvant therapies. Protons cannot address your situation nor mine. But your entry is not clear on what treatments you have had. RT, HT, any of these? As far as side effects, my only issue is very minor in that I have some light hot flashes, and that's from the HT. You will be able to stay very active and should consider following your doctors advice with a visit to a major cancer center. I'm afraid that if you have not had HT then the time is now, then in a couple months, radiation. Again the initial result will be a bit of fatigue, but then you will be back in business as usual. Good luck, Fred, and hurry back and tell us your trek back to undetectable.

Tony

Fred,

I am curious as to why Protons are not available to you? You are not that far from Loma Linda. Met several people from Colorado while there. John

Fred:

For info on proton you can go to the second thread from the top "Helpful Hints---" and read the threads on proton.  Also, there is info on www.protonbob.com (testimonials) and the Loma Linda proton site is www.protons.com.   Proton radiation is being used quite abit now for surgery salvage.  I have referred one gentleman for this and after a year he is doing well with no problems.  Best wishes on your search for what is best for YOU.

Dutch

John and Dutch:
    I am overwhelmed by your support and your willingness to help. I will start my research on Proton Beam Radiation tomorrow. I may have further questions to tap your first hand experiences.
  Thank you doesn't seem like enough... but ..thank you,
Fred
   As an aside:  I sit on the board of the "Prostate Cancer Education Council" in Denver, Co. It is loosely associated with the Colorado University Hospital and is the brain child of Dr E. David Crawford. Dr Crawford is one of the foremost prostate cancer doctors in the country. He is published often in Urology jourinals and JAMA. The mission of PCEC ( the education council) is to promote awareness to prostate cancer and to hold free Testings around the country, PSA and DRE. However we deal with detection of first time PC and with info connected to our site on available treatments.  We have not dealt with recurring PC. I know first hand how frightening and perplexing this situation can be. This thread and website is wonderful and the response from those who have had first time treatment and "salvage" treatment is INVALUABLE. The connection to this site and thread will be put on the PCEC (www.pcaw.com) website. This will expose many more men to information that can save their lives.

Fred

as Dutch said:

  Our responsibility now is to educate men about Pca, PSA and the importance of early detection

Dave,
Great to hear from you. Hope you are doing well. Always loved reading your posts and great RT knowledge. I can say that IMRT was a breeze for me, but remember I stopped at 38 treatments as I was a post op patient. Take care and hope to see you more.

Tony