Friday, 14 August 2015
Patients experiencing biochemical failure after prostatectomy for prostate cancer, often receive salvage radiation therapy
Patients experiencing biochemical failure — defined as an increase in prostate-specific antigen (PSA) level — after prostatectomy for prostate cancer often receive salvage radiation therapy (SRT) to control the disease and prevent metastases.
However, despite SRT, some patients still exhibit biochemical failure. Now, a long-term, single-center study, published online July 9 in the American Journal of Clinical Oncology, has demonstrated that outcomes for 61 men who experienced a biochemical recurrence after surgery, including a subset of 34 men who experienced failure twice (once after surgery and once after SRT), are robust.
The median overall survival was 13.6 years for the men in the study who had two biochemical recurrences and 14.7 years for the men who had just the one recurrence after surgery, report the authors, led by D. Nathan Kim, MD, PhD, from Texas Oncology in Waco.
Furthermore, the 10-year prostate-cancer-specific, metastasis-free, and castration-resistant-free survival (from the time of PSA failure after SRT) rates were all in excess of 70% for the men who had two biochemical recurrences.
The new retrospective data might be of service to clinicians in discussions with anxious patients because there is a "paucity" of prospective data about this clinical scenario, the authors suggest.
The extensive follow-up period makes the study one of the longest in the literature. Median follow-up was 126 months after SRT and 112 months after SRT failure. Most studies have a median follow-up of less than 90 months after SRT.
"Because of our long-term follow-up, we were able to make observations in those patients who recurred despite SRT," the authors write.
Although their study was of a single group of men, and thus not comparative in any way, the authors observe that another study on natural history after PSA failure demonstrated that the median time to distant metastasis was 8 years after PSA failure after radical prostatectomy (without SRT), and roughly one in three patients developed distant metastases within 5 years without radiation therapy.
"In our series, distant metastases-free survival at 5 years was 94% for all patients, and was 75% for those who failed after SRT," the authors report.
"The study suggests that SRT is effective in preventing prostate-cancer-specific mortality and decreases the rate of distant metastases," the team writes.
The new study also raises the issue of the timing of radiation therapy after prostatectomy.
Patients with pathologic T3 disease or positive margins are candidates for postoperative radiation therapy, said Colleen A.F. Lawton, MD, past chair of the American Society for Radiation Oncology (ASTRO) board of directors, who was not involved in the study.
This recommendation is based on the American Urological Association/ASTRO guidelines on the use of adjuvant and SRT after prostatectomy, which is endorsed by the American Society of Clinical Oncology (Int J Radiat Oncol Biol Phys. 2013;86:822-828).
PSA levels determine what's next for these patients, Dr Lawton told Medscape Medical News.
Patients with adverse pathologic features, such as seminal vesicle invasion, positive surgical margins, and extraprostatic extension without evidence of disease recurrence (i.e., undetectable PSA levels), are candidates for adjuvant radiation therapy (ART), said Dr Lawton, who is from the Medical College of Wisconsin in Milwaukee.
Patients who show increases in PSA at any time after surgery are candidates for SRT, she explained.
Patients with pathologic T3a disease should see a radiation oncologist and discuss whether they are candidates for ART or SRT, Dr Lawton said. "The issue is that many patients do not consult with their radiation oncologist," she told Medscape Medical News.
The new study findings do not challenge the guidelines, she suggested.
The study provides food for thought, but is not practice-changing.
"The study provides food for thought, but is not practice-changing," said Dr Lawton.
Nevertheless, in this study, the authors indicated that 70% of their patients would have been candidates for ART based on their pathologic stage and margin status. They emphasize that "without concrete evidence from randomized clinical trials, one must seriously consider the advantages and disadvantages of ART versus SRT."
"The decision of whether to use ART or SRT remains an area of active debate, and prospective randomized trials are currently underway to attempt to answer this question," they add.
The authors were referring to the RAVES trial (NCT00860652), which is a phase 3 study investigating the timing of radiation therapy for prostate cancer with high-risk features.
Active surveillance is indicated for men with a PSA level of 10 ng/L or less, a Gleason score below 6, and a pathologic disease stage of T2a or less, said Dr Lawton. She explained that if patients have pathologic T3 disease and undetectable PSA, other factors should be taken into account when deciding on management, including the presence of comorbidities.
The analysis involved 61 men treated at the University of Texas Southwestern Medical Center in Dallas from 1992 to 2000 who underwent SRT following biochemical recurrence after prostatectomy.
Biochemical recurrence of the disease after surgery was defined as a persistently detectable PSA level of at least 0.05 ng/mL or two consecutive PSA increases of at least 0.1 ng/mL that triggered initiation of SRT.
Failure of SRT was defined as a single increase in PSA of at least 2 ng/mL from nadir levels, two consecutive PSA increases of at least 0.2 ng/mL, initiation of salvage treatment, or clinical disease recurrence.
At 10 years, overall survival was 67%, freedom from PSA failure was 33%, prostate-cancer-specific survival was 84%, and distant metastases-free survival was 84% for the men who failed SRT.
Pathologic T-stage, Gleason score, seminal vesicle involvement, and pre-SRT PSA were associated with freedom from PSA failure.
For patients who failed SRT, the median time to biochemical recurrence after SRT was 30 months.
A total of 19 patients (68%) received androgen-deprivation therapy.
Early SRT failure correlated with a significant decrease in distant metastases-free survival and prostate-cancer-specific survival. Ten-year distant metastases-free survival from SRT was 43% (recurrence at 1 year or sooner) versus 91% (recurrence at 1 year or beyond).
The study begs the question of whether biochemical failure is an important surrogate for clinical care in prostate cancer. Dr Lawton indicated that it is an important surrogate; however, there is no absolute proof about its being associated with survival.
Am J Clin Oncol. Published online July 9, 2015.
Thursday, 30 July 2015
Sunday, 26 July 2015
Wednesday, 15 July 2015
Please excuse the self indulgence, but this was one of the proudest moments of my life. When I look at the boxes of work produced over those 4 years, it filled my car. It was a slog! I met some amazing people and had experiences that were beyond imagination. I had cancer surgery in first year, then smuggled a 4x4 into Serbia in my second. My third year fades from memory, unlike my fourth, in Johannesburg, which changed my life and will stay precious to me always. Without the support of my wonderful wife Beverley, it would have been impossible. In Carlisle Cathedral today, I couldn't help but feel a bit special. Daniel Sencier BA hons. I like it! Now I need to think about a career!
Wednesday, 1 July 2015
Thursday, 25 June 2015
Saturday, 20 June 2015
By Michael Howerton on February 04, 2014
One of the confounding characteristics of cancer has long been that the body’s usually active patrol against viruses tends to leave deadly cancer cells alone to fester, mutate and spread.
Saturday, 13 June 2015
by RORY CLEMENTS, Daily Mail 12th June 2015
A once-a-day pill has been approved in Britain for use in the early stages of prostate cancer following a massive trial that showed it could reduce the risk of the disease progressing in 42 per cent of men.
Prostate cancer is known to 'feed' on the male hormone testosterone, but Casodex, which is a hormone-based drug, 'starves' the cancer by preventing testosterone getting to it. It works on receptors in the cells.
In the trial, Casodex was used alongside standard treat-ments of surgical removal of the prostate, radiotherapy or merely careful watching of the disease's development, often slow.
Those on the drug fared far better than those on a dummy pill. Many men's biggest fear is that treatment for prostate cancer will make them impotent and kill their love life.
Casodex has a vital advantage over some other hormone treatments in that it significantly reduces the risk of impotence.
Whereas other drugs block production of testosterone, Casodex allows testosterone to remain in the blood stream, but it doesn't allow it to get to the cancer.
Some hormone treatments cut off the supply of testosterone completely and in effect amount to 'chemical castration'. The new study, the world's biggest-yet prostate cancer trial, followed the fortunes of over 8,000 men in 23 countries, including Britain.
Dr Heather Payne, consultant clinical oncologist at the Middlesex Hospital, London, says: 'Most men feel that to be actually doing something to prevent the cancer coming back actually makes you feel more positive.
'And you don't want to have a treatment that is going to make you feel so dreadful that you start wondering whether it's worth having the medication. But this drug is well tolerated and doesn't harm the quality of life.'
Casodex has been used for many years in treating advanced prostate cancer, but this is the first time it has been studied and approved for use in the early stages.
'Before, people would just have the surgery or radiotherapy,' says Dr Payne. 'In this study, they had the surgery or radiotherapy and were then randomly given either Casodex or a placebo to see if that would improve results over the surgery or radiotherapy alone - and the drug did.'
Not only did it stop the disease progressing in 42 per cent of men against those who took the placebo, it also prevented the cancer spreading to the bones in a third of the patients. When the cancer gets to the bones it can be extremely painful.
Widower Alec Taylor, 70, a retired English teacher of Primrose Hill, North London, discovered he had early prostate cancer in 1997 after seeing his GP for a checkup and agreed to go on the Casodex trial.
He learned last week that he was one of those taking the real pill rather than the placebo. He is presently clear of cancer.
He said: 'The bad news was that I had cancer - the good news was that the tumour was very small. My treatment started in January 1998. The radiotherapy went on for 32 sessions over six weeks. I thought I'd go potty.'
'Then they mentioned the Casodex trial and I was told I could go on it if I wanted. I thought it was for the benefit of science, so I agreed to it and stuck it for two years. The great difficulty was to remember to take the things, same time every day. I missed only four.'
Saturday, 30 May 2015
Our 18 months in South Africa, we agree, was the most amazing time of our lives. Beverley and I visited all 10 provinces, and also toured in Zimbabwe, Mozambique, Zambia, Botswana, and Swaziland. You can go on holiday to these places, but living there and experiencing the people and culture for so long, was breathtaking.
Back in the UK now for a short while before the next great adventure, Thailand, and this time it's for 3 years! From Bangkok we can reach out to Australia, India and Japan in just 6 or 7 hours, but within a 1 to 2 hour flight are amazing countries such as Malaysia, Cambodia, Indonesia, Borneo, Burma, China, Vietnam and Singapore, just to name a few. Comparing Johannesburg to Bangkok is difficult, they both have millions of inhabitants and a wet season, but nothing else is the same. Where Jozi is around a mile above sea level, hot and very dry, Bangkok is at sea level, even hotter and extremely humid. Thailand is positively safe when compared to South Africa, but no harm in staying cautious when traveling anywhere abroad these days. When I get there, I'll give you a taste of what it's like.
Thailand has strict rules about criticising the government or royal family and it's not allowed in any way, any where, ever. You can end up in prison quickly, so as a blogger, I intend to stay completely respectful to Thai laws, customs and regulations. All my research indicates that the country is most welcoming and a cultural feast to outsiders. The cost of living is even cheaper than South Africa, but I'm told to buy my clothes and shoes in the UK because they don't cater for men my height.
After Thailand, what next? Well, who can plan ahead more than 3 years?
Friday, 29 May 2015
When I had a routine health check-up eight years ago, my cholesterol was so high that the laboratory thought there had been a mistake. I had 9.3 millimoles of cholesterol in every litre of blood — almost twice the recommended maximum.
It was quite a shock. The GP instantly prescribed statins, the cholesterol-lowering drugs that are supposed to prevent heart disease and strokes. For eight years, I faithfully popped my 20mg atorvastatin pills, without side effects. Then, one day last May, I stopped. It wasn’t a snap decision; after looking more closely at the research, I’d concluded that statins were not going to save me from a heart attack and that my cholesterol levels were all but irrelevant.
When I informed my GP of my decision three months later, I wasn’t entirely honest. Rather than say I was sceptical about the drugs, I told my doctor I’d quit the statins because they were causing pain in my arm.
He didn’t bat an eyelid. Evidence from the drug industry published this month – evidence I suspect was heavily reliant on data from the drug industry, as Dr James Le Fanu pointed out on these pages last week – may suggest that side effects are uncommon, but previous studies have found that one in five people on statins suffers adverse side effects, from muscle pain and diarrhoea to memory loss and blurred vision.
The GP simply suggested I try another brand of statin. The sooner the better, he said, given that I’d already been off my prescription for three months. “Hang on,” I said. “Could you give me a blood test first?” When the results came back, he was amazed that my total blood cholesterol was lower than when I’d been on statins. After three months without the pills, it was 5.4mmol/l (5.4 millimoles per litre of blood) compared with 5.7 mmol/l a year earlier.
The only major changes I’d made to my lifestyle since coming off statins were eliminating sugar (including alcohol and starchy foods such as bread) and eating more animal fat. Many experts now believe that sugar is emerging as a true villain in the heart-disease story; while after decades of demonisation, saturated fat has been acquitted of causing heart disease by a recent “meta” analysis of 70 studies by Cambridge University.
Typically, I was eating red meat three or four times a week and enjoying butter, full-fat milk and plenty of eggs. You would have thought that after three months on a diet so high in saturated fat, my cholesterol would have shot back up to pre-statin levels — but no, it came down and has stayed down seven months on. Not only that, but my levels of LDL (so-called bad cholesterol) were also lower than when I’d been on statins, and my ratio of HDL (so-called good cholesterol) to LDL was under four for the first time, an excellent sign, according to medical wisdom.
Not that I cared about any of this.
Yes, it was the statins that originally reduced my cholesterol levels so dramatically. But so what? I believe that high cholesterol has been a scapegoat for too long. Yes, it may, in some circumstances, be an indicator of heart disease but there is no evidence of a causal link. In my view, high total blood cholesterol or high LDL levels no more cause heart attacks than paramedics cause car crashes, even though they are present at the scene.
Just lowering cholesterol with drugs without sorting out the dietary and lifestyle factors that actually cause heart disease is nonsensical. Besides, there are plenty of other, more reliable indicators of heart-disease risk. What further astonished my GP was that on these indicators I was now apparently better off in other ways than when I’d been on statins. My blood pressure was down. For the first time in years, I was slimmer, especially around the belly. My triglycerides — a type of blood fat with a causal link to heart disease — were lower than at any time in the preceding eight years. My fasting blood glucose was at the optimum level, whereas a year earlier it had been too high. My total white blood count — a marker of inflammation — was lower.
My blood test for a marker called glycated haemoglobin (A1c), high levels of which are associated with heart disease and overall mortality, were bang on normal. Finally, my level of c-reactive protein (CRP) — a protein that rises in response to inflammation — was extremely low. So, biochemically, I was in excellent shape, better than when I’d been on the statins. “Have you taken up running?” asked my bemused GP.
No, I’d always run. For years, I’d exercised three times a week, eaten plenty of fish, refrained from smoking and tried to keep my stress levels low. The only thing I’d changed was my intake of sugar and animal fat.
That check-up was seven months ago and now, at 58, I’m not on a single tablet. My GP is happy. I feel better than I have in years and, at the same time, deeply concerned about proposals advising even wider use of statins.
Until 2005, statins were prescribed only to those with at least a 30 per cent or greater risk of having a heart attack within 10 years. This was then reduced to a 20 per cent risk. Now, draft NHS guidelines would have them dished out to those with just a 10 per cent risk — in other words, most men over the age of 50 and most women over the age of 60.
I am a vascular surgeon. Before founding a private clinic in Dorset 11 years ago, specialising in varicose veins, I worked in the NHS for 13 years. Back then, I didn’t question medical guidance on cholesterol, and thought statins were a wonder drug. And so they probably are, for men who have heart disease — not necessarily because they lower cholesterol, but because they may cut other risks such as the inflammation-marker CRP. Exercise, weight loss and omega 3 supplements also lower CRP.
But what about other groups — women, the elderly and people like me who have not been diagnosed with heart disease? The evidence that we will benefit from cholesterol-lowering drugs is ambiguous at best. The 2011 Hunt 2 study, one of the most recent and largest, followed 52,000 men and women in Norway aged 20-74 with no pre-existing heart disease, for 10 years.
The results for women were crystal clear. The lower a woman’s total cholesterol, the greater her risk of dying, either of heart disease or anything else, including cancer. This reflects findings in previous studies.
For men, high cholesterol was associated with heart disease and death from other causes. But so, too, was low cholesterol — below 5mmol/l. Again, this is only an association, not a causal link. A range of between 5mmol/l and 7mmol/l was the optimum level. Guess what? This is already the national average. In addition, numerous studies have linked high cholesterol levels with increased longevity in the elderly.
As for me, I have not been diagnosed with heart disease, and nobody in my family has had a heart attack. However, all four of my paternal uncles and my sister have diabetes. Research from Canada, published last year in the BMJ, has shown that statins raise the risk of diabetes, so that gives me little faith. The controversy over these drugs was reignited last week when Prof Sir Rory Collins from Oxford University warned that doctors’ hesitancy about prescribing them to those at risk could cost lives.
GPs are, by definition, generalists. They don’t have time to read and analyse data from every paper on every medical condition. Even so, in a recent survey by Pulse magazine, six in 10 GPs opposed the draft proposal to lower the risk level at which patients are prescribed statins. And 55 per cent said they would not take statins themselves or recommend them to a relative, based on the proposed new guidelines.
If that doesn’t speak volumes, I don’t know what does.