Tuesday, 25 October 2016

Gleason 6? Should I wait before having radical treatment?

What does it mean to have a Gleason score of 6 (or 7 or 8-10) ?

The lowest Gleason score of a cancer found on a prostate biopsy is 6. These cancers may be called well-differentiated or low-grade and are likely to be less aggressive – they tend to grow and spread slowly. 
Cancers with Gleason scores of 8 to 10 may be called poorly differentiated or high grade. These cancers tend to be aggressive, meaning they are likely to grow and spread more quickly.
Cancers with a Gleason score of 7 may be called moderately differentiated or intermediate grade. The rate at which they grow and spread tends to be in between the other 2.
The use of active surveillance for the management of nonaggressive prostate cancer has soared to record highs in Sweden in recent years, providing a "benchmark" for the rest of the world, according to the authors of a new study.
From 2009 to 2014, the proportion of Swedish men with very-low-risk cancer choosing active surveillance increased from 57% to 91% and, among those with low-risk cancer, it rose from 40% to 74%, report the investigators, led by Stacy Loeb, MD, MSc, from New York University in New York City. The authors used data from a nationwide prostate cancer registry.
Low-risk prostate cancer and its prolonged natural history can be safely managed with active surveillance and the deferred, as-needed use of curative treatment, such as prostatectomy and radiation therapy, explain Dr Loeb and her coauthors, who include academics from three different Swedish universities.
Notably, in Sweden, medical records distinguish between active surveillance, which includes blood testing, biopsy, and imaging, and watchful waiting, which is a passive approach that waits to see whether clinical symptoms develop before medical intervention.
The new Swedish active surveillance data, which are an update from an earlier report that extended only to 2011, are the "highest rates yet reported" and "should serve as a benchmark to compare the use of active surveillance for favorable-risk disease around the world," write the authors.
Currently, the United States does not measure up very well, suggest the authors. Most low-risk disease is treated immediately, they observe.
"We hope that our data from Sweden will showcase that…the use of this management option is growing around the world and will encourage US men who are diagnosed with low-risk prostate cancer to ask their doctor about it," Dr Loeb told Medscape Medical News.
Dr Loeb has been an ongoing supporter of the use of active surveillance. At a press conference at the 2014 annual meeting of the American Urological Association (AUA), she declared the "era of active surveillance" had arrived. This meeting featured multiple studies indicating large upticks in its use.
The new study from Dr Loeb and colleagues is published online today in JAMA Oncology.
The high rate of active surveillance in Sweden "is likely a goal to which we should aspire on both sides of the Atlantic," says Matthew R. Cooperberg, MD, MPH, from University of California San Francisco in an accompanying editorial.
Dr Cooperberg also says that active surveillance rates "are still too low" in the United States.
Still, progress is being made, he suggests.
Dr Cooperberg says that data from some prospective, community-based registries have shown use of active surveillance "skyrocketing" to 40% to 50% for low-risk disease in the current decade, up from historical rates of about 10% (JAMA. 2015;314:80-82).
He also highlights guidance newly endorsed by the American Society of Clinical Oncology that surveillance is "not merely an option" for men with low-risk disease but rather is the "preferred alternative" for any clinically localized, Gleason 3 + 3 cancer.
But Dr Cooperberg makes no mention of guidance from the most influential organization in the United States with regard to prostate cancer: the AUA.
The AUA has not updated its guidelines for the management of localized prostate cancer, which include active surveillance recommendations, since 2007.
With regard to Sweden, the study authors describe some "potential facilitating factors" for the "rapid uptake" of active surveillance.
For example, in 2007 national guidelines were issued that recommended active surveillance for men with low-risk prostate cancer and a life expectancy of 10 to 20 years. Then, in 2014, the life expectancy limit was abandoned, and active surveillance was recommended for all men with very-low-risk prostate cancer.
The study authors also believe it is important that Sweden's National Prostate Cancer Register provides "real-time feedback" to practices on their adherence to these national guidelines and also in annual reports publicly available online.
Furthermore, the Swedish healthcare system "is dominated by equal access, tax-funded care without financial incentives for clinicians to recommend curative treatment," the authors observe.
Overall, 32,518 men with a median age of 67 years were diagnosed with favorable-risk prostate cancer during the study period.
These included 4693 men with very-low-risk disease (clinical stage, T1c; Gleason score 6 or less; prostate-specific antigen [PSA], <10 ng/mL; PSA density <0.15 ng/mL/cm3; and <8-mm total cancer length in 4 positive biopsy cores).
A total of 15,403 men with low-risk disease (including all men in the very-low-risk group) (T1 to T2; Gleason score, 6 or less; and PSA <10 ng/mL), and 17,115 men had intermediate-risk disease (T1 to T2; Gleason score, 7; and/or PSA, 10 to 20 ng/mL).
Use of active surveillance for intermediate-risk disease was much lower — only 19% of cases in 2014.
In a press statement, Dr Loeb said that more US men opting for active surveillance "could go a long way toward reducing the harms of screening by minimizing overtreatment of non-aggressive prostate cancer."
Dr Cooperberg agrees.
In his editorial, he writes: "A default assumption that most low-risk prostate cancers do not need immediate treatment would completely shift the balance of benefits and harms for prostate cancer early detection efforts, and it will prove invaluable in reframing the ongoing national debate regarding optimal screening policy."

Nick Mulcahy: October 20, 2016

Monday, 24 October 2016

As a small boy...

As a small boy, if I wanted to get some worry off my mind, I'd write it down, then relax, I could forget it. It's the same with this blog, so when I'm worried, I write it here, it helps.

My Dad died of prostate cancer at the age of 68, and here I am, nearly at 65. Surgery/radiotherapy wasn't an option for him, treatment hadn't advanced to that point, all he could do was wait for the inevitable.

A recent study seemed to argue that whether you have surgery or radiotherapy, or even no treatment at all, you will still die at the same time as you would have, regardless. I didn't see the logic in that. How could it be? But it's still in the back of my mind.

I had no recurrence of PSA in the 2/3 years following surgery, and that's good, because that would have meant the cancer was still there and multiplying fast enough to cause big problems. Now I'm coming up to the 6 year mark, and in a few weeks my PSA tests reach an interesting point. It's between about 6 and 9 years that you find out if a few microscopic rogue cells drifted off, before/during surgery and settled elsewhere in the body, in a bone, maybe a lymph node, waiting to reveal themselves in the distant future. Usually, but not always, a recurrence at that stage is very slow, after all it took perhaps 7 years to get big enough to be even noticed.

If it happens, and mine hasn't and hopefully never will, there is a very good guideline to how fast that growth will be. If you had PSA testing in the years before treatment, the 'doubling rate' will be about the same as you can expect now.

That's why I asked a good friend (though I've only met him twice) to approach my doctor in England for those early results of mine, as I want to feel prepared. I'm hoping to have them with me later this week, and I hope to get some reassurance. Of course the 'golden ticket' is still zero PSA, then there is no doubling rate to worry about.

There, now I can forget it!

Monday, 17 October 2016

How to handle a relapse after treatment for prostate cancer

I discovered this blog, so if you do have a relapse, there's some very useful stuff here...

Marc B Garnick, M.D., discusses what biochemical recurrence means and what your options are. " Am I going to die?” This is the first question a patient usually asks me when a follow-up blood test reveals that his prostate-specific antigen (PSA) level has risen after he has already undergone treatment for prostate cancer (usually a radical prostatectomy or radiation therapy). The fear is understandable: When PSA levels rise to a certain threshold after prostate cancer treatment, the patient has suffered what is known technically as a biochemical recurrence, sometimes also referred to as a biochemical relapse or stage D1.5 disease. Whatever term is used, it means that prostate cancer remains within the prostate after radiation therapy, that it survived outside the excised area after radical prostatectomy, or that it has reappeared in metastatic form in other tissues and organs. In most cases the cancer remains at a microscopic level, and many years will pass before any physical evidence of it is detectable on a clinical exam or any abnormalities are seen on a bone scan or CT scan.
That’s usually of small comfort to the patient whose PSA has risen. It’s emotionally traumatic to go through treatment for prostate cancer, thinking it is cured, and then learn that it might have come back. For many men, it’s as if they’re dealing with another diagnosis of cancer, except this time it’s much worse because there is less likelihood of getting cured. A man’s confidence and sense of safety may be shattered, especially because the popular misconception is that when prostate cancer recurs, it is deadly.
Which brings me back to my patient’s question: “Am I going to die?”
The simple answer is yes, eventually — we all do — but you may not die from prostate cancer. Of course, with prostate cancer, nothing is simple. This may be one disease, but it can appear in multiple forms, so every diagnosis or recurrence requires individualized assessment and intervention. To start thinking about the salient issues, see “Four key questions.”

Four key questions

If your PSA rises after prostate cancer treatment, answering four key questions will help you and your doctor determine next steps:
  • What were your risk characteristics, such as Gleason score, PSA, and cancer stage, at the time of diagnosis? (See Table 1.)
  • What type of treatment did you have? That will help determine your next treatment options.
  • How long has it been since you underwent initial therapy for prostate cancer? This helps indicate how aggressive follow-up treatment needs to be.
  • How fast is your PSA rising, as determined from several evaluations?
In practical terms, biochemical recurrence means that you are now dealing with a chronic disease, like diabetes, so that your clinical monitoring will have to increase and you may need to choose or adjust treatment to meet new challenges. Unfortunately, we don’t yet have sufficient research to provide clear guidance about when a second therapy (referred to as salvage therapy) should be considered after biochemical recurrence, and which type of salvage therapy is most effective in particular circumstances. (Salvage therapy is a terrible term, but I use it in this article because it is the standard name for follow-up therapy.)
For those who have already suffered a biochemical recurrence after being treated for prostate cancer — or dread each follow-up blood test because it might signal such a recurrence — this article explains what a rising PSA after treatment really means and what your treatment options are.

Table 1: Predictors of biochemical recurrence at time of diagnosis

Although a number of clinical factors contribute to your risk of relapse after treatment, the parameters below provide a simpler assessment of your chances of biochemical recurrence, based on your clinical profile at the time of diagnosis. For more sophisticated estimates, based on specific risk factors, see Figures 1 through 3.
Low risk (33% chance of biochemical recurrence within five years)Gleason score less than or equal to 6
andPSA less than or equal to 10 ng/ml
andCancer stage T1c or T2a
Intermediate risk (50% chance of biochemical recurrence within five years)Gleason score of 7 (if 3+4)
and/orPSA greater than 10 but no greater than 20 ng/ml
and/orCancer stage T2b
High risk (85% chance of biochemical recurrence within five years)Gleason score of 7 (if 4+3), or 8 or more
and/orPSA greater than 20 ng/ml
and/orCancer stage T2c or more

Defining biochemical recurrence

As you are probably aware, both normal prostate cells and prostate cancer cells manufacture PSA. That is why the PSA level should fall to undetectable levels in men treated with radical prostatectomy, in which the prostate is removed, but is not likely to drop to zero in men treated with radiation therapy, even when treatment is successful. This is because after radiation therapy the prostate gland remains intact and can recover some function. This is also true if you received hormone therapy as part of your radiation treatment: As you recover, testosterone levels rise, and so does your PSA.
The real challenge is defining what constitutes a biochemical recurrence after a particular type of therapy. There is no consensus on this issue, but the working guidelines are summarized in Table 2.

Table 2: Guidelines for determining biochemical recurrence

Initial therapyPSA thresholdComments
Radical prostatectomy0.2 ng/ml on at least two successive testsSome physicians continue to use a higher threshold of 0.4 ng/ml or greater
Radiation therapy (external beam or brachytherapy)Three successive elevations in PSA compared to nadir (low point), regardless of actual reading, according to the American Society for Therapeutic Radiology and OncologyMany oncologists use a working definition that biochemical recurrence has occurred if PSA levels are greater than 1–2 ng/ml 12 to 18 months following initial treatment.
Ideally, post-treatment PSA levels should be less than 0.5 ng/ml, but this is rare; levels of 0.6–1.4 ng/ml may occur.
Neoadjuvant hormone therapy and radiation therapyUnknown
Further muddying the water, it is not clear what PSA levels should be in men who have undergone neoadjuvant hormone therapy in addition to radiation therapy. Hormone therapy suppresses levels of testosterone; once the therapy is stopped, testosterone levels rise, and PSA generally increases rapidly until the hormonal environment stabilizes.
Moreover, some men who have undergone external beam radiation therapy or implantation of radioactive seeds (brachytherapy) experience a phenomenon known as PSA bounce, a temporary spike in PSA that does not necessarily indicate recurrence. Studies offer varying conclusions about how common this phenomenon is, probably because they use different definitions of what constitutes a “bounce.” Until more is known, if you have had some form of radiation therapy for prostate cancer and experience a spike in your PSA level, it is wise to ask your physician whether this could be a PSA bounce.

A common challenge

Rising PSA after initial treatment often comes as a shock to the person affected, but it’s actually a common problem. Studies indicate that biochemical recurrence affects roughly 15%–30% of men initially thought to be curable with localized treatment of prostate cancer. Certainly if you find yourself in this situation, you are not alone.
For example, a study published in the Journal of Urology, which followed 3,478 men who underwent radical prostatectomy for prostate cancer, found that 32% were likely to suffer a biochemical recurrence within 10 years. (The study actually followed patients an average of a little more than five years, but used actuarial tables to predict outcome at 10 years.) Another study, published in the Journal of the American Medical Association, examined the outcomes for 1,997 men who underwent radical prostatectomy and were followed for an average of a little more than five years, and found that 15% experienced biochemical recurrence in that time. (For further details about these studies, see “Biochemical recurrence after surgery,” below.)

Biochemical recurrence after surgery

Pound CR, Partin AW, Eisenberger MA, et al. Natural History of Progression after PSA Elevation Following Radical Prostatectomy. Journal of the American Medical Association 1999;281:1591–7. PMID: 10235151.
Roehl KA, Han M, Ramos CG, et al. Cancer Progression and Survival Rates Following Anatomical Radical Retropubic Prostatectomy in 3,478 Consecutive Patients: Long-Term Results. Journal of Urology 2004;172:910–14. PMID: 15310996.
Other studies indicate that a similar (or perhaps slightly higher) percentage of men treated with radiation therapy will experience a biochemical recurrence (see “Biochemical recurrence after radiation therapy,” below). For example, a study of 1,449 men with prostate cancer treated with brachytherapy, published in the Journal of Urology, found that anywhere from 19% to 26% experienced biochemical recurrence within 12 years, depending on the definition of recurrence. It should be noted that nearly half the men were also treated with either neoadjuvant hormone therapy or a combination of brachytherapy and external beam radiation therapy, which may have increased the success of treatment or delayed recurrence. And a study comparing the outcomes of 393 men who received different doses of external beam radiation therapy for prostate cancer, published in the Journal of the American Medical Association, found that 19.6% of those who underwent high-dose radiation therapy experienced biochemical recurrence within five years, while 38.6% of those who underwent conventional-dose radiation therapy did.

Biochemical recurrence after radiation therapy

Potters L, Morgenstern C, Calugara E, et al. 12-Year Outcomes Following Permanent Prostate Brachytherapy in Patients with Clinically Localized Prostate Cancer. Journal of Urology2005;173:1562–6. PMID: 15821486.
Zietman AL, DeSilvio ML, Slater JD, et al. Comparison of Conventional-Dose vs High-Dose Conformal Radiation Therapy in Clinically Localized Adenocarcinoma of the Prostate: A Randomized Controlled Trial. Journal of the American Medical Association 2005;294:1233–9. PMID: 16160131.

Assessing your personal risk

Several factors contribute to your risk profile. One important factor is whether you have localized or more advanced disease at the time of biochemical recurrence. As indicated in Table 1, your pretreatment numbers such as Gleason score and pathological cancer stage will provide some indication of whether the recurrence is local or metastatic. Also important is how much the PSA increased within a given time period (known as the PSA velocity) before treatment, and how long it takes for PSA to double in value (known as PSA doubling time) after treatment.
For example, two studies that looked at the relationship between PSA velocity and post-treatment outcomes in men treated for early-stage prostate cancer found that men with a PSA velocity of 2 ng/ml or less in the year before diagnosis had a much better prognosis than those whose PSA velocity was greater than 2 ng/ml per year (see “PSA velocity and prognosis,” below). In a study of 1,095 men treated with surgery, published in the New England Journal of Medicine, investigators found that men with a PSA velocity greater than 2 ng/ml in the year preceding diagnosis were 50% more likely to experience biochemical recurrence than the men whose PSA velocity was less than that. These men were also likely to experience biochemical recurrence faster and faced a greater likelihood of dying from prostate cancer than the other men. In the second study, involving 358 men treated with external beam radiation therapy, published in the Journal of the American Medical Association, researchers found that men with a PSA velocity greater than 2 ng/ml in the year preceding diagnosis were 80% more likely to experience biochemical recurrence than the others, and less likely to survive (see Table 3). Similarly, post-treatment PSA doubling time can also be used to assess the likelihood that disease is local or metastatic and provide insight into prognosis.

Table 3: PSA velocity before diagnosis and estimated chances of survival

An analysis of PSA velocity in the year preceding diagnosis reveals that it can predict the likelihood of survival seven years after external beam radiation therapy. (Similar findings have been reported for an analysis of men who underwent radical prostatectomy.)
Overall risk profile (based on PSA, Gleason score, cancer stage)When PSA velocity is less than or equal to 2 ng/ml per yearWhen PSA velocity is greater than 2 ng/ml per year
Low risk100%81%
High risk96%76%
Source: Journal of the American Medical Association, July 27, 2005.
When the post-treatment PSA level doubles in less than six months, for example, and certainly when it doubles in less than three months, the cancer has most likely spread and therefore requires systemic treatment. Research has also shown that the length of time it takes PSA to double can be used to estimate likelihood of whether disease will become clinically evident (detected by symptoms and scans) following biochemical recurrence (see Table 4).

Table 4: PSA doubling time and outcome five years after biochemical recurrence

A study involving 2,809 men who were treated with surgery and subsequently experienced biochemical recurrence (defined as a PSA of 0.4 ng/ml or more) found a clear relationship between PSA doubling time and eventual clinical outcomes.
PSA doubling timePercentage of men without prostate cancer*
Less than 6 months38%
6–11 months46%
12 months–9 years, 11 months62%
10 years or more87%
*No clinical indication of local or systemic disease, based on digital rectal examination, transrectal ultrasonography, biopsy, or bone scan.
Source: Mayo Clinical Proceedings, June 2001.
Of course, estimates of average likelihood of progression are simply that — estimates — and may not indicate what is going on in your own case. So to better determine whether your cancer recurrence is localized to the prostate or has spread elsewhere, your doctor will not only look at your pretreatment numbers, but also restage the disease by repeating some of the tests you had at the time of your initial diagnosis. You will likely undergo a bone scan and an abdominal pelvic CT scan. You may also undergo a ProstaScint scan, which uses monoclonal antibodies tagged with a radioisotope to identify metastatic prostate cancer in lymph nodes and other areas in the pelvis. It’s important to note, however, that not all doctors recommend such tests because in most men who experience rising PSA, these scans will usually not reveal any clinical evidence of metastases.

PSA velocity and prognosis

D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA Velocity and the Risk of Death from Prostate Cancer After Radical Prostatectomy. New England Journal of Medicine2004;351:125–35. PMID: 15247353.
D’Amico AV, Renshaw AA, Sussman B, Chen MH. Pretreatment PSA Velocity and Risk of Death from Prostate Cancer Following External Beam Radiation Therapy. Journal of the American Medical Association 2005;294:440–7. PMID: 16046650.

Knowing whether and when to act

If your PSA indicates that biochemical recurrence has occurred — or if you are tracking your PSA closely, to determine whether you may need to consider treatment — you probably want to know what your options are. But as you evaluate options, consider not only what to do, but whether and when to act.
Unfortunately, experts don’t agree about when salvage treatment for recurrent prostate cancer should begin, or which salvage treatments are best. Of course, if you experience biochemical recurrence and the cancer appears aggressive — as indicated by your pretreatment risk profile (see Table 1) or a PSA doubling time of less than six months — your physician is likely to recommend immediate treatment, probably with hormone therapy, to delay metastases.
But many other men will find themselves in a gray area, with clinical profiles and PSA doubling times that are not sufficient to trigger immediate salvage therapy. If you are in this category, your physician may recommend waiting to treat until your PSA rises to a particular level. That means you may have more frequent PSA testing, which can be nerve-racking but is necessary to detect progression earlier. (For more insight into what this feels like, see “A couple’s story: Tracking PSA,” below.)
Although many men diagnosed with biochemical recurrence will want to take immediate action to stop the cancer, going ahead with therapy for the sake of simply doing something may cause more harm than good. The risks and complications of surgery or radiation, already high when delivered after an initial diagnosis of prostate cancer, may become even greater when these therapies are delivered as salvage after biochemical recurrence. Data are sparse on the side effects of salvage therapy, simply because not many studies have been done on the topic, but I always advise patients in this situation to consider that any complications of the initial therapy may be increased if their abdominal and pelvic areas are subjected to a second therapy. For example, some research indicates that the likelihood of developing urinary incontinence after prostatectomy is greater following salvage treatment (where it may affect 20%–60% of men) than when it is the first mode of treatment (where it may affect 2%–15% of men).
It’s also wise to consider the impact of further treatment if you have other diseases besides prostate cancer, such as diabetes, cardiovascular disease, or a pulmonary disease such as emphysema. If you do, it is likely that you are on medications for these disorders, and are already dealing with significant health challenges and risks. Undergoing additional treatment for prostate cancer may add to these risks, or may require that you readjust medications you are taking.
Finally, remember that you have time to make an informed decision about whether and when to undergo additional treatment for prostate cancer following biochemical recurrence. The evidence shows that you can expect to live for many more years. For example, the Journal of the American Medical Association study cited earlier, which reported that 15% of men experienced biochemical recurrence in a little over five years, also analyzed what happened to the men afterward. The authors found that it took an average of eight years for the cancer to metastasize to the bones, and the men survived another five years after that — for a total of 13 years, on average, after biochemical recurrence.
Remember that average survival times are based on studies of men treated in the past, and sometimes as long as 10 or 20 years ago. What’s more, some of these studies (including the Journal of the American Medical Association study cited above) included men who did not undergo further treatment after biochemical recurrence occurred. It’s likely that these men would have survived for a longer time if they had received additional treatment after biochemical recurrence was detected (although longer survival would come at the cost of treatment side effects). For these reasons, the “average” chances may be much better for a man treated today. And such averages can never predict what will happen in your particular case. That’s why, when I talk with patients about studies like this one, I encourage them to make decisions based on their own risk profile. As shown in Figures 1 through 3, your particular risk will vary, depending on factors such as PSA level at diagnosis, PSA doubling time, and Gleason score. Finally, when it comes to evaluating your options, much will depend on whether you were treated initially with surgery or radiation therapy, with or without hormone therapy.

Options for men who had surgery

How long after treatment it took for the PSA to rise and how quickly it rose provide important clues to whether it’s likely that your cancer is localized or metastatic. Generally speaking, the prognosis is worse for men whose PSA never becomes undetectable after surgery, or rises quickly a short time after treatment. Prognosis is better for men whose PSA rises slowly and begins to rise a long time after treatment. A few scenarios will help clarify what the options are in each situation.
Some men learn right away that they have residual disease. The surgeon sends any tissue excised during the operation to a pathologist for analysis. If the pathologist finds positive margins — meaning that he found cancer cells at the borders, or margins, of the excised tissue — this means that you may need to undergo radiation treatment to eradicate the cells remaining in the prostate area.
Scenario 1. Sometimes the PSA level never becomes undetectable after a prostatectomy. This situation, which is fortunately rare but among the most challenging to treat, means either that some cancer cells remained in the prostatic fossa (tissue left behind during surgery in the area once occupied by the prostate gland), or — more likely — that micrometastases had already spread beyond the prostate. A man in this situation may need additional therapy right away. The options offered may be radiation or hormone therapy, or both, or an investigational therapy.
Scenario 2. Sometimes the PSA falls to undetectable levels for several months following radical prostatectomy, and then begins to creep up. Typically, a man in this situation learns during one of his follow-up tests that he has experienced a biochemical recurrence. If the PSA level rises within the first year after surgery, it usually indicates metastatic disease. The treatment option most often offered is hormone therapy (either intermittent or continuous).
Scenario 3. The PSA does not begin to rise until a year or more after surgery. This is more likely to indicate localized disease, although it is possible that the disease has spread. Your treatment options depend on the PSA doubling time — how quickly PSA is increasing. If your PSA doubles in less than six months, and certainly less than three months, your doctor may recommend treating the area again, but this time with radiation or hormone therapy, in order to eradicate the disease.
Scenario 4. The PSA rises a year or more after surgery, but the doubling time is slow (a year or longer). This is probably the best scenario of all, as it indicates that the cancer may be localized and not aggressive. In this situation, you may opt for active surveillance — monitoring PSA and periodically having other tests, but not necessarily choosing an active intervention right away.

Salvage options after radical prostatectomy

Most men who experience a biochemical recurrence after prostatectomy and decide to undergo treatment have three options. The best strategy depends on your risk profile and comfort with side effects.

Radiation therapy

Many men opt to undergo salvage radiation therapy. Although few studies have been done to evaluate long-term results, many men do respond to salvage treatment. One study involving 368 men who had initially undergone radical prostatectomy, for example, found that five years after undergoing salvage radiation therapy, 46% remained free of biochemical recurrence, and 92% were still alive; at eight years, 35% remained free of biochemical recurrence, and 80% were still alive. Other studies have reported that salvage radiation therapy is likely to be most effective in men whose Gleason score, PSA level and doubling time, and other clinical features indicate less aggressive disease (see “For more information: Salvage radiation therapy,” below).
Side effects. Be aware that radiation therapy delivered after a prostatectomy markedly increases the likelihood of impotence and may increase the likelihood of incontinence. If you are already incontinent after surgery, then having radiation therapy is likely to make the problem permanent. For that reason, most men who become incontinent after surgery will wait until they regain control over their bladder or rectum before undergoing postoperative radiation therapy.

For more information: Salvage radiation therapy

Buskirk SJ, Pisansky TM, Schild SE, et al. Salvage Radiotherapy for Isolated Prostate Specific Antigen Increase after Radical Prostatectomy: Evaluation of Prognostic Factors and Creation of Prognostic Scoring System. Journal of Urology 2006;176:985–90. PMID: 16890677.
Sengupta S, Christensen CM, Zincke H, et al. Detectable Prostate Specific Antigen Between 60 and 120 Days Following Radical Prostatectomy for Prostate Cancer: Natural History and Prognostic Significance. Journal of Urology 2006;176:559–63. PMID: 16813889.
Stephenson AJ, Shariat SF, Zelefsky MJ, et al. Salvage Radiotherapy for Recurrent Prostate Cancer after Radical Prostatectomy. Journal of the American Medical Association2004;291:1325–32. PMID: 15026399.

Radiation with hormone therapy

Another option is to undergo hormone treatment while undergoing salvage radiation therapy, because this may increase the effectiveness of radiation therapy.

Hormone therapy

If the PSA doubling time is less than six months, indicating that the cancer is aggressive, radiation therapy may not be adequate, as it is likely the cancer has already spread. In that case, a better option is a full course of hormone therapy, which can delay the time of onset to bone metastasis.
But other considerations also come into play. If you are sexually active and want to remain so, hormone therapy may not be the right option for you. Or you can opt for erectile-sparing hormone therapy, which involves a single agent like bicalutamide (Casodex), or bicalutamide and finasteride (Proscar) (see “For more information: Erectile-sparing hormone therapy,” below). Another option is to go on intermittent hormone therapy, in effect taking occasional “holidays” from treatment. This allows men to recover some quality of life while at the same time reducing levels of testosterone, which fuels the cancer.
If you are elderly (defined as having less than 10 years of life expectancy), you may not want the full spectrum of hormone therapy because it causes other complications.

For more information: Erectile-sparing hormone therapy

Boccardo F, Rubagotti A, Barichello M, et al. Bicalutamide Monotherapy Versus Flutamide Plus Goserelin in Prostate Cancer Patients. Journal of Clinical Oncology 1999;17:2027–38. PMID: 10561254.

Salvage options after radiation therapy

If your initial cancer treatment was radiation therapy and you experience a biochemical recurrence, the salvage treatment you choose depends on whether you received external beam radiation therapy or brachytherapy, as well as whether you also received hormone therapy.

Salvage prostatectomy

When one of my patients experiences biochemical recurrence following radiation therapy, the first question I expect to hear is, “Can we just go in and take it out?” Salvage prostatectomy is a possibility for some men, but it is not used often, simply because it’s such a difficult operation. Radiation therapy causes scar formation and the development of fibrous tissue in the treated area, so that a surgeon may be unable to distinguish among different types of tissue. It may be difficult, for example, to distinguish the specific boundaries of the rectum and the bladder because of prior radiation scarring. Some highly skilled surgeons can perform a salvage prostatectomy, but the larger consideration is whether it is worth doing at all.
One could make a strong argument that in most cases, rising PSA after radiation therapy indicates systemic disease, and any type of local therapy — even salvage prostatectomy — is not going to solve the larger problem of cancer cells that have metastasized elsewhere. For those cells, you need hormone therapy.

Salvage radiation therapy

In certain unusual circumstances, if recurrent cancer is found only in a limited part of the prostate gland, it may be possible to place radioactive seeds in the area to eradicate the cancer. The techniques for performing this are still under investigation, and long-term data on effectiveness are not yet available. Be aware that it is not known whether this additional radiation will increase the risk of other types of cancers.


Another option, also appropriate only when a localized area of cancer is found, is cryotherapy. This freezes the prostate gland to kill any remaining cancer cells. This highly specialized treatment is not practiced widely, and substantial complications have been reported.

Metastatic disease: Hormone therapy

If your doctor determines that you have a metastatic rather than a localized recurrence, hormone therapy is your best option — and it is appropriate whether you initially underwent a radical prostatectomy or radiation therapy. Before a man who has experienced biochemical recurrence decides to have hormone therapy, however, the first question is whether he has had it before. Some men who were at intermediate or high risk of relapse (see Table 1) and decided to have radiation therapy initially probably also had hormone therapy beforehand because this increases the chances that initial therapy will succeed. If the patient had a hard time of it, in terms of side effects, he may not want to consider hormone therapy again.
Hormone therapy works by reducing testosterone levels. Because testosterone fuels the growth and development of prostate cancer, reducing levels of this fuel helps stop cancer from progressing — or at least slows the rate of progression.

Hope for the future

Experiencing biochemical recurrence can be emotionally devastating — there’s no doubt about it. But research continues about how best to treat men who experience a relapse following initial therapy for prostate cancer, and it is likely that new therapies will emerge in the coming years. In the meantime, stay informed about your treatment options and work with your doctor to determine whether it’s time to consider some type of salvage therapy.

Tuesday, 11 October 2016

Can you help with my research?

I'm currently undertaking research for 'Airboat Afrika'. http://www.airboatafrika.com/home-port/ 

Contact: Daniel@AirboatAfrika.com

Airboat Afrika is an international operator 
and the largest airboat supplier in Africa, 
most recently working 
with the U N World Food Programme (WFP).

The CEO, Christian Grosch, is a friend of mine, and we met while I was working in Johanennesburg. 

I'm looking at the possibilities of airboat provision here in South East Asia, in particular, linked to flood disaster areas

Due to the high population density, they immediately require emergency services starting with search & rescue, evacuation and subsequently, distribution of food, tents, medical equipment etc.

In flooded areas, airboats can reach most areas that a helicopter can, and often act as a static base.
The driver/pilot needs just a few days training. The overall cost of supply/operation is less than 20% that of a helicopter.

Airboat Afrika have worked with the World Food Programme, most recently in Malawi, where our equipment made a vast difference to the humanitarian outcome. 

I'm looking for contacts that you may have in any of the large Charities/NGO's regardless of where they are, or how small the contact might be. 
Contacting the right people in these companies is difficult without it feeding through internally. So if you have a brother, sister, daughter, son or any other friend or relative working for any charity or NGO, I would be grateful for their contact details. 

Alternatively you may like to forward my contact details to them. 

Examples of Charities/NGO's (but there are 100's more)...

Red Cross
Save the Children
World Food Programme
International Rescue Commitee
Wildlife Conservation Society

Many thanks for your help,

Best wishes,

Daniel Sencier 



Friday, 7 October 2016

Is the 'Cyberknife' the answer to your prostate cancer treatment?

I had the privilege of being contacted by the organisers before this announcement in Boston USA this week. They wanted my opinions on what could be the biggest breakthrough in prostate cancer treatment for many years. I was asked not to release any information until today...
E-mail from Sherry Feldburg (MSL Group)...
At the largest annual gathering of radiation oncologists (ASTRO meeting) taking place next week in Boston, a new study evaluating the safety and efficacy of 5 CyberKnife treatment sessions (delivered using SBRT) for prostate cancer will be among a handful featured in a press conference. ASTRO had a choice of more than one thousand abstracts, but chose to feature the CyberKnife prostate cancer data because it has the potential to change clinical practice.
The 21-site study found that 97% of men with low- and intermediate-risk prostate cancer had excellent cancer control five years post treatment; this is similar to control rates with other common treatments including radiation therapy and surgery. So from a clinical standpoint, the study confirms that CyberKnife is at least as effective as these other treatments.
However, from a quality of life and cost perspective, CyberKnife treatment has significant advantages.
It is more cost effective for the healthcare system (½ the cost of IMRT, the most commonly used external beam treatment for prostate cancer) and easier on patients because it’s noninvasive (no surgery involved) and requires a much shorter course of treatment -- just five days – than conventional radiation therapy. Another key differentiator is that CyberKnife SBRT uses built-in motion management technology to track the tumor during treatment, providing confidence that radiation is delivered with accuracy and that radiation exposure of surrounding healthy tissue and organs in minimized.
In a healthcare environment in which every dollar counts and there is an emphasis on addressing the needs of the whole patient, this study may be the lynchpin that propels CyberKnife SBRT to become a go-to treatment choice for men with low- and intermediate-risk prostate cancer.
Would you be interested in pursuing a story that educates men on this 5-day treatment option which doesn’t require surgery and provides excellent cancer control at five years’ post-treatment?  I’d be happy to share the study abstract under embargo and can also arrange a pre-brief with one of the lead investigators of the study to discuss the results as well as an Accuray executive. 
REMINDER that these data are under embargo until it’s presented at ASTRO on Monday, September 26 at 8:15 a.m. ET. Your story cannot post until after that time.

ASTRO 2016: SBRT Offers Patients With Prostate Cancer High Disease Control and Low Toxicity in Fewer Treatments

Key Points

  • At 5 years following SBRT, 97% of patients were free from prostate cancer progression.
  • Specifically, in the low-risk group, the 5-year relapse-free survival rate was 97.3%, which is superior to the 93% historical comparison disease-free survival control rate.
  • Fewer than 2% of all patients experienced serious side effects in the 5 years following SBRT.
High-dose stereotactic body radiotherapy (SBRT) for men newly-diagnosed with low- or intermediate-risk prostate cancer results in shorter treatment times, low severe toxicity, and excellent cancer control rates, according to research presented by Meier et al at the 58th Annual Meeting of the American Society for Radiation Oncology(ASTRO). The study is the first large, multi-institutional study of SBRT in prostate cancer with long-term follow-up.
Although prostate tumors generally respond well to radiation therapy, the possibility of radiation exposure to healthy tissue in the genitourinary and gastrointestinal systems can be of concern. SBRT is an advanced technique that precisely targets high doses of radiotherapy to the tumor in a small number of fractions, simultaneously avoiding surrounding tissue and reducing toxicity to noncancerous cells. The technique has become the standard of care for many nonsurgical lung cancer patients, as it limits exposure to the heart and surrounding lungs. When treating tumors in the prostate, SBRT avoids the adjacent bladder, sex organs, and rectum.
“Single-institution studies on the use of SBRT as the primary treatment for prostate cancer have illuminated the treatment as a cost-effective and faster alternative to IMRT,” said Robert Meier, MD, lead author of the study and a radiation oncologist at Swedish Medical Center in Seattle. “Our study is the first to contribute multicenter data that support the use of SBRT as front-line therapy for men with prostate cancer.”
Study Details
A total of 309 men with newly diagnosed prostate cancer were enrolled in the trial at 21 community, regional, and academic hospitals across the U.S. Eligible patients had either low-risk disease (CS T1–T2a, Gleason 6, PSA < 10) (n = 172) or intermediate-risk disease (CS T1c–T2b with either Gleason 7 and PSA < 10, or Gleason 6 and PSA 10–20). All of the men received SBRT via a nonisocentric robotic platform, with a radiotherapy dose to the prostate of 40 Gy administered in five treatment sessions of 8 Gy each. Intermediate-risk patients received a dose of 36.25 Gy to the seminal vesicles. Concurrent and adjuvant androgen ablation therapy were prohibited among study participants.
Primary outcomes included genitourinary and gastrointestinal toxicities and relapse-free survival. Researchers measured toxicity using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. Biochemical failure was assessed using the ASTRO-consensus and the nadir+2 definitions. Overall survival was measured as a secondary outcome for the study. Actuarial overall survival and relapse-free survival were calculated with the Kaplan-Meier statistical method. Median follow-up was 61 months.
At 5 years following SBRT, 97% of patients were free from prostate cancer progression. In low-risk patients, the cancer control rates was superior to historical controls. Specifically, in the low-risk group, the 5-year relapse-free survival rate was 97.3%, which is superior to the 93% historical comparison disease-free survival control rate (P = .014). Actuarial 5-year overall survival was 95.6% for the entire cohort. Actuarial 5-year nadir+2 relapse-free survival was 97.1% for all patients, representing 97.3% of low-risk and 97.1% of intermediate-risk patients. Actuarial 5-year ASTRO relapse-free survival was 92.3% and 91.3% for low- and intermediate-risk groups, respectively.
Fewer than 2% of all patients experienced serious side effects in the 5 years following SBRT. Five grade 3 genitourinary side effects were reported in four of the 309 study participants. There were no reported grade 4 or 5 toxicities, nor any grade 3 gastrointestinal toxicities. Between half and two-thirds of patients experienced less serious side effects, with rates of 53 and 59% for grade 1 genitourinary and gastrointestinal toxicities, respectively, and rates of 35 and 10% for grade 2 genitourinary and gastrointestinal toxicities, respectively. These side effects were usually temporary.
“Our results illustrate how advanced technology has radically improved our ability to target cancer,” said Dr. Meier. “After following patients for more than 5 years, we found that serious side effects from a brief course of SBRT were uncommon and that cancer control rates were very favorable compared to historical data. Our trial confirms that SBRT may be preferable to other treatment approaches for newly-diagnosed cases of prostate cancer, including more aggressive disease.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.