Questioning Medicine: Prostate Cancer Screening

Andrew Buelt, DO, and Joe Weatherly, DO, are family medicine residents in St. Petersburg, Fla. Together, they co-produce the podcast Questioning Medicine, where they deconstruct issues confronting today's clinicians. In this guest blog, Buelt gives his take on the overuse of prostate cancer screenings

Let the Prostate Be

As prostate cancer awareness month just ended, prostate cancer screening seemed a fitting subject for this week's blog.

Those who know the evidence might think this argument pits European practices against our own domestic actions. Almost like a Ryder Cup for prostate screening. However, I recently saw that almost 50% of patients admit to undergoing lubed finger insertions and blood tests, which we know to be fairly inaccurate, in the last 12 months.

In a Research Letter in JAMA Internal Medicine by Sammon et al., the fact that so many physicians are still screening for prostate cancer makes my evidence-based medicine soul cringe. In a 2012 survey, the authors found that among 114,544 respondents, 37% had undergone screening. Higher socioeconomic status nearly doubled a man's odds of being screened (odds ratio 1.91, 95% CI 2.69-3.34).

Prostate cancer screening has been placed in the no-go category by the U.S. Preventive Services Task Force and the Choosing Wisely campaign, as well as by many other major medical associations.

Even the American Urological Association, which stands to lose the most money from reduced screening, states, "Men ages 55 to 69 ... should talk with their doctors about the benefits and harms of testing ...." In my opinion, they deserve a standing ovation for speaking to the evidence and not to the money, as the American College of Obstetrics and Gynecologists has with pelvic exams.

I suppose some physicians will try to argue that rectal exams are not unpleasant or uncomfortable for the patient, as many did in the comments section of my pelvic exam post. However, if you really believe that, it's probably been a while since your last rectal exam.

The Screening Process

There are two parts to prostate screening: the digital rectal exam (DRE) and the prostate-specific antigen (PSA) blood test. Guided by evidence, here's a look at harms and benefits.

First, is the index finger so sensitive and accurate that it can really detect cancer with the DRE? A little common sense would tell us "no chance," and the evidence seems to support that.

In a study published in the Annals of Surgical Oncology by Richie et al., among 644 asymptomatic men, 241 had an abnormal DRE or elevated PSA. And of the 163 who underwent further ultrasound or biopsy, 77% were found to have normal results.

A retrospective analysis of 14 studies by Hoogendam et al. suggested that the positive predictive value of the DRE was only 28% (95% CI 0.20-0.36), meaning that out of 100 men who were diagnosed by their physician's finger, 72 did not actually have cancer. Plus, according to an analysis by Collins et al., 25% of the time when cancer was found after DRE, the biopsy located it in a different part of the prostate!

So unless your patient has a fecal impaction there is probably very little reason to perform a DRE.

What about the PSA blood test? Its accuracy is also riddled with way too many false positives and false negatives. This is one of those tests that has led to serious rates of overdiagnosis.

Only about 24% of those who undergo prostate biopsy because of elevated PSA actually have prostate cancer (Studer and Collette). The study included 162,243 men, and about 76% of those with a PSA over 3 ng/mL were false positives.

In a study published in the Journal of the National Cancer Institute, which reported the results of The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial, Andriole et al. found barely any benefit with PSA screening and DRE. The cumulative mortality rates in the intervention arm were 3.7 compared to 3.4 per 10,000 person-years in the control arm.

Authors of the European Randomized Study of Screening for Prostate Cancer (ERSPC) found a 20% reduction in prostate cancer deaths with PSA. Yet, when you look at actual numbers, it paints a much different picture. The ERSPC study estimated that 1,410 men would need to undergo screening, and 48 more cases of prostate cancer would need to be treated, for one life to be saved. Meaning 48 men will possibly endure erectile dysfunction or urinary incontinence for life, for every one life saved.

When the USPSTF looked at the evidence, they found for every 1,000 men screened for 10 years, roughly 220 had a positive result. About 110 subsequently get a true diagnosis of prostate cancer, 50 get a complication from treatment, and at most one life is saved.

I'll repeat the most important part of that rant: one out of a thousand is saved! At least 50 men will have a serious complication and about 100 will have to undergo anxiety and sleepless nights for a disease they don't even have.

Just under half of those in a different study with a positive screen and negative biopsy, 40%, admitted to worrying about prostate cancer "a lot" or "some of the time." This could qualify as harmful to a man's mental health.

Better Left Unchecked

Finally, in an estimate by Draisma et al., almost 50% of those diagnosed with prostate cancer would have never developed any symptoms of disease had they been left unchecked. Too often people will argue a 10 to 12 years' increase in survival with those screened for prostate cancer.

The problem is the very small or almost nonsignificant increase in mortality. I do not care if my patient survives longer with a disease, as long as the age of mortality remains the same.

After all, the reason we treat hypertension, high cholesterol, or screen for cancer is to have people live longer; not to die at the same age.

Of course, there are physicians out there with anecdotal evidence of catching life-threatening prostate cancer in early stages during a routine DRE or PSA, and will therefore insist they are great tests, just like the pelvic exam.

What shouldn't be forgotten is all of the men who now wear a diaper, can't get an erection, or can't sleep from high anxiety.

So why even have the test available? Possibly if the patient has a positive family history. It seems to increase the patient's risk two or three times above the standard rate of incidence, according to Whittemore et al.

Thus, instead of one out of 1,000, it is 2.5 out of 1,000. At that point, it might be worth at least a conversation. It is also decent to trend the success of prostate cancer treatment. However, as a screening tool it's like swimming with a shark: rarely will it kill you, but it will likely to leave you mentally or physically scarred, feeling vulnerable, and with high anxiety.

Tomado de: Medpagetoday.com  By Andrew Buelt, DO

‘Prostate cancers’ not ‘prostate cancer’ – revealing the many faces of ‘one’ disease

New research published today in Genome Biology shows that RNA sequencing could lead the way towards more personalized treatments for prostate cancer. In this guest post, Dr Iain Frame, Director of Research at Prostate Cancer UK discusses what this could mean for patients and health services, and what more is needed to provide effective support and treatment for men with prostate cancer.

We are used to hearing and talking about prostate cancer as a single disease.  Albeit a disease with its tigers and pussycats – the tigers being the aggressive cancers that move out of the prostate gland to other parts of the body, and the pussycats being those cancers that may never cause any harm and won’t go on to kill.  But it’s never quite as simple as that is it?

More and more we hear clinicians and research scientists talk about ‘prostate cancers’ plural. This is largely down to the introduction of genomic sequencing which has allowed researchers to identify and examine large numbers of prostate tumors, which initiate and progress in different ways. Add to this, the genomic variations in the men themselves, and suddenly the world of detecting and treating cancers of the prostate becomes a lot more complicated – not that it was ever simple to begin with!

What the paper published today by Drs Collins and Wyatt from the Vancouver Prostate Centre does so well is apply state-of-the art RNA sequencing technology to a real life situation. So on top of the information we know at the whole genome level, they looked at which genes were being used and disrupted at the point when the tumor was collected. Being able to match this up with how these men and their tumors had responded to different treatments meant that the researchers could then see which treatments work best for the different tumor types.

So in theory, by knowing more about the tumor and the man who has the tumor, researchers will be able to develop more personalized or tailored treatments for individuals. As a result, clinicians will be armed with a much clearer idea as to which treatments will work most effectively and speculation will be a thing of the past.

However, there is a ‘but’.  The researchers here only looked at 25 tumors and were surprised by the sheer number of genomic differences between them. Forty-thousand  men are newly diagnosed with prostate cancer each year in the UK and there are 250,000 men in this country living with the disease – so how much variation will there be when the number of tumors examined in this way increases?

The challenge lies in how we translate this fantastically elegant research into real life benefits for these men and those at risk of prostate cancer.  And what’s more – let’s not kid ourselves that it is only prostate cancer that is looking to tailor treatments – every other disease is working to the same aim, putting tremendous pressure on health services, which will need to cope with the increased expense of diagnosing and managing disease at an individual level.

At Prostate Cancer UK, we strongly support the development of new tailored treatments for men with prostate cancer. However, allied to that aim is an ambition to be able to take some men out of the system – those men whose cancer will never spread.

We feel that alongside developing better treatments, the global research community needs to develop a more robust risk assessment tool that can be used in multi-ethnic populations, delivered through primary care reasonably simply and in a cost-effective way. By doing this in prostate cancer we should be able to concentrate limited healthcare resources on those who need it most – those with, or at high risk of, aggressive prostate cancers.

There is absolutely no doubt that this is a really exciting time for prostate cancer research.  The results from this research will help build a better picture of what is going on and I’m confident that in the future it can lead to important health benefits for men with, and at high risk of, aggressive prostate cancer.

But that fight needs resources – both financial and human – to succeed.  It is clear that we must keep building on research successes such as the one reported here,  but for this to be possible, more funding is needed to support more scientists through their research endeavors in order to achieve real benefits for men.

Tomado de blogs.biomedcentral.com

Datos a largo plazo confirman los beneficios de las pruebas diagnósticas para la detección del cáncer de próstata

Datos a 13 años confirman los beneficios en términos de mortalidad, pero los investigadores dicen que todavía no se justifica realizar pruebas de detección a nivel poblacional

Antecedentes

El Estudio aleatorizado europeo para la detección del cáncer de próstata (European Randomised study of Screening for Prostate Cancer, ERSPC) ha demostrado reducciones significativas en la mortalidad por el cáncer de próstata después de 9 y 11 años de seguimiento, pero las pruebas diagnósticas para la detección de la enfermedad aún son controvertidas debido a los acontecimientos adversos, como el sobrediagnóstico. Proporcionamos resultados actualizados sobre la mortalidad por cáncer de próstata con seguimiento hasta 2010, con análisis revisados a los 9, 11 y 13 años.

Métodos

ERSPC es un ensayo multicéntrico, aleatorizado, con una base de datos centralizada predefinida, plan de análisis y grupo de edad principal (55-69 años), que evalúa las pruebas del antígeno específico de la próstata (prostate-specific antigen, PSA) en ocho países europeos. Se identificaron hombres elegibles de 50-74 años de edad a partir de registros poblacionales y se les asignó aleatoriamente, mediante números aleatorios generados por ordenador, a someterse a pruebas de detección de la enfermedad o a no realizarse ninguna intervención (control). Los investigadores no conocían las asignaciones de grupo. El criterio de valoración primario fue la mortalidad por cáncer de próstata en el grupo de edad principal. El análisis se realizó por intención de tratar. Realizamos un análisis secundario con corrección para el sesgo por selección debido a la no participación. En los centros franceses solo se comunicaron los datos de incidencia y no mortalidad a los 9 años de seguimiento. El estudio está registrado en Ensayos controlados actuales con el número ISRCTN49127736.

Resultados

Con datos revisados a los 13 años de seguimiento, se diagnosticaron 7408 casos de cáncer de próstata en el grupo de intervención y 6107 casos en el grupo de control. La tasa de incidencia de cáncer de próstata entre los grupos de intervención y de control fue de 1,91 (IC 95% 1,83-1,99) después de 9 años (1,64 [1,58-1,69] incluida Francia), 1,66 (1,60-1,73) después de 11 años y 1,57 (1,51-1,62) después de 13 años. La tasa de mortalidad por cáncer de próstata fue de 0,85 (0,70-1,03) después de 9 años, 0,78 (0,66-0,91) después de 11 años y 0,79 (0,69-0,91) a los 13 años. La reducción absoluta del riesgo de muerte por cáncer de próstata a los 13 años fue de 0,11 por cada 1000 años-persona o de 1,28 por cada 1 000 hombres asignados aleatoriamente, lo que es equivalente a evitar una muerte por cáncer de próstata por cada 781 (IC 95 %490-1 929) hombres invitados a realizarse las pruebas de detección o uno por cada 27 (17-66) casos de cáncer de próstata adicionales detectados. Después del ajuste por no participación, la proporción de las tasas de mortalidad por cáncer de próstata en los hombres evaluados fue de 0,73 (IC 95% 0,61-0,88).

Interpretación

En esta actualización, el estudio ERSPC confirma una reducción sustancial en la mortalidad por cáncer de próstata atribuible a las pruebas de PSA, con un aumento sustancial del efecto absoluto a los 13 años en comparación con los hallazgos después de 9 y 11 años. Pese a nuestros hallazgos, aún se considera un prerrequisito la cuantificación adicional de daños y su reducción para que tenga lugar la introducción de las pruebas de detección a nivel poblacional

Tomado de Univadis

Referencias

Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate cancer mortality: results of the European Randomised Study of Screening for Prostate Cancer (ERSPC) at 13 years of follow-up. The Lancet. 2014;doi:10.1016/S0140-6736(14)60525-0.

New Early Detection Test for Prostate Cancer

More than 1 million men will undergo a prostate biopsy this year, but only about one-fifth of those biopsies will result in a cancer diagnosis.

The reason is that the traditional prostate cancer screening test – a blood test to measure prostate specific antigen, or PSA – does not give doctors a complete picture.

Now, the University of Michigan Health System has begun offering a new urine test called Mi-Prostate Score to improve on PSA screening for prostate cancer. The test incorporates three specific markers that could indicate cancer and studies have shown that the combination is far more accurate than PSA alone.

“Many more men have elevated PSA than actually have cancer but it can be difficult to determine this without biopsy. We need new tools to help patients and doctors make better decisions about what to do if serum PSA is elevated. Mi-Prostate Score helps with this,” says Scott Tomlins, M.D., Ph.D., assistant professor of pathology and urology at the University of Michigan.

Researchers validated the new test on nearly 2,000 urine samples. Mi-Prostate Score, or MiPS, was significantly more accurate than PSA alone for predicting cancer as well as predicting aggressive prostate cancer that is likely to grow and spread quickly.

Mi-Prostate Score developed from a discovery in the lab of Arul Chinnaiyan, M.D., Ph.D., in 2005 of a genetic anomaly that occurs in about half of all prostate cancers, an instance of two genes changing places and fusing together.

This gene fusion, T2:ERG, is believed to cause prostate cancer. Studies in prostate tissues show that the gene fusion almost always indicates cancer.

The new urine test looks for the T2:ERG fusion as well as another marker, PCA3. This is combined with serum PSA measure to produce a risk assessment for prostate cancer. The test also predicts risk for having an aggressive tumor, helping doctors and patients make decisions about whether to wait and monitor test levels or pursue immediate biopsy.

“This combination test is not designed to say definitively at diagnosis whether a man has aggressive prostate cancer, but it can provide a more accurate estimate of the likelihood of having cancer and the likelihood of that cancer being aggressive,” Tomlins says.

The test is available to anyone but requires a request from a doctor.

Prostate cancer statistics: 238,590 Americans will be diagnosed with prostate cancer this year and 29,720 will die from the disease, according to the American Cancer Society

University of Michigan Health System. "New early detection test for prostate cancer." ScienceDaily, 25 Sep. 2013. Web. 16 Jan. 2014

New Tool Predicts Survival in Advanced Prostate Cancer

But a good prognostic tool has been lacking in this setting, particularly since a new chemotherapy called cabazitaxel as been approved by the U.S. Food and Drug Administration as another line of treatment.

Now researchers at the Duke Cancer Institute have developed a tool for doctors to forecast the potential survival of individual patients, enabling faster, more accurate information on whether to try additional rounds of treatment or seek clinical trials.

The findings are published online in the Journal of the National Cancer Institute.

"Our findings provide a prognostic tool that relies on information that is routinely collected in clinical practice and should be readily available," said Susan Halabi, Ph.D., professor of biostatistics and bioinformatics at Duke and lead author of the study. "For patients with metastatic prostate cancer who are appropriate candidates for second-line chemotherapy, this model can be helpful for guiding care. It could also be used during clinical trials to assign patients in risk groups based on measurable criteria."

In their study, Halabi and colleagues developed and validated the new prognostic tool using two different clinical trials of prostate cancer patients whose cancer returned after they had undergone a regimen of docetaxel, the standard first-round chemotherapy that is used after hormone treatments have been ineffective.

The researcher's approach provides an understanding of the complex interactions between the host, the tumor factors and clinical outcomes.

By plugging in 17 variables -- including pain intensity, measurable disease, race, age, body mass index and others -- the researchers determined that certain key factors were relevant to overall survival.

Of the 17 variables, nine were determined to be predictive of survival: how a patient's physical performance is rated on a scale of 0-2; the length of time since the first chemotherapy ended; how extensive the disease is; whether the disease has spread to the liver, lungs or other organs; how much pain the patient is experiencing; the duration of hormone use; and levels of hemoglobin, prostate specific antigen and alkaline phosphatase.

Two of those factors had not previously been used in prognostic models -- the duration of hormone therapy and the amount of time since the first-round docetaxel treatment.

"Several new treatments have been developed in recent years that prolong life for men with metastatic prostate cancer," Halabi said. "As a result, it's increasingly important to provide a clear prognostic picture that can help guide both doctors and patients to the best options."

This tool is available online at  https://www.cancer.duke.edu/Nomogram/secondlinechemotheray.html

Duke Medicine. "New tool predicts survival in advanced prostate cancer." ScienceDaily, 18 Oct. 2013. Web. 15 Nov. 2013.

Reducing the Side Effects of Treatment for Prostate Cancer

New research published in BioMed Central's open access journalBMC Medicine reassessing clinical data from trials, which investigate ways of treating side effects of therapy for prostate cancer, finds that tamoxifen, an anti-estrogen used to treat breast cancer, is also able to suppress gynecomastia and breast pain in men.

Prostate cancer is one of the most common cancers in men and early treatment is usually very successful. Androgen-suppression therapy is often used to slow down progression of advanced disease. However, unwanted side effects of anti-androgen treatment, such as breast enlargement, can stop men from seeking treatment for their cancer.

Testosterone can drive the growth of prostate cancer and anti-androgens are used to inhibit prostate cancer growth by preventing testosterone from binding to androgen receptors. But receptors in cells within the testes are also blocked and start to make more testosterone to compensate. Some of this extra testosterone is converted into estrogen which is responsible for development of breast tissue and other breast events. Anti-estrogens work by jamming the estrogen receptor, while aromatase inhibitors prevent the conversion of testosterone into estrogen.

A collaboration between the German Cochrane Center and University Clinic Erlangen combined data from four independent clinical trials each looking at the management of breast events (during treatment for prostate cancer) with tamoxifen.

A meta-analysis of all four trials showed that tamoxifen reduced the risk of both gynecomastia and breast pain at 3, 6, 9, and 12 months of treatment compared to men who received no treatment. Overall, treatment with tamoxifen was more successful in reducing breast symptoms than treatment with an aromatase inhibitor (anastrazole) or radiotherapy.

Although there is no long term data available, few of the men treated with tamoxifen, either as preventative or therapeutic treatment, stopped taking their medication during their year of treatment. There were also no significant adverse effects.

Dr Frank Kunath, who led this study explained, "Not all men will suffer gynecomastia during anti-androgen therapy. However, if men know that there is a successful option for reducing the breast symptoms associated with treatment for prostate cancer they may be more likely to see their doctor when symptoms of cancer first appear, and consequently reduce the number of unnecessary deaths."

BioMed Central Limited. "Reducing the side effects of treatment for prostate cancer."ScienceDaily, 24 Aug. 2012. Web. 6 Sep. 2012.