Prostate cancer news update: Saturday, August 23

Todays’ reports contain some interesting data, although it is not entirely clear how they should best be applied in the diagnosis and potential management of patients at risk:

  • A study of patient preferences and decision making about how to be treated
  • Why some Brazilian men reject digital rectal examination (fewer that you might expect)
  • The natural history of high-grade prostatic intraepithelial neoplasia (HGPIN)
  • The potential of ferumoxtran-10 (Combidex) in diagnosis of lymph node metastases

Sommers et al. have attempted to gain greater understanding of how newly diagnosed prostate cancer patients make decisions about their preferred treatment for prostate cancer. The study was based on a survey of 167 men at four academic medical centers between 2004 and 2007. The data analysis is based on several assumptions and complex statistical methodology. However, the basic reults are as follows: Patient preferences were affected by a range of behavioral, demographic, and health factors. The strongest predictor of treatment was the type of physician seen (radiation oncology vs urology) at the time of the survey. Age and tumor grade also were found to be strongly predictive of treatment. In general, the theoretical concept of quality-adjusted life years (QALYs) were not found to predict treatment choice. The authors concluded that whicle patient decisions are shaped by reasonable behavioral and demographic influences, actual treatment choices appear to bear little relation to these patient preferences, and instead seem to demonstrate a strong personal association with clinician specialty. 

Romero et al. have investigated why patients reject digital rectal examination (DRE) as a screening tool  in a group of 450 Brazilian men participating in a prostate cancer educational program consisting of lectures, PSA testing, and DRE. DRE was rejected by 8.2 percent of the attendees. The refusal rate was not affected by age, prostate cancer family history, school level, family income, or PSA level. Patients with a prior history of DRE had a lower rejection rate than those undergoing DRE for the first time (4.4 vs. 10.4 percent). Men with mild or no lower urinary tract symptoms rejected DRE more frequently than those with moderate or severe symptoms (9.6 vs. 1.4 percent). Misconceptions about prostate cancer screening were identified in 84.4 percent of those rejecting DRE vs. 46.9 percent of controls (p = 0.002); 43.7 percent expected severe discomfort in the group that rejected DRE vs. 28. 1 percent in the control group; fear of finding a cancer during DRE was present in 34.4 percent of patients that refused DRE vs. 46.9 percent of controls; and 53.1% of patients rejecting DRE indicated that it was a source of shame vs. 15.6 percent of patients in the control group.

Guzzo et al. set out to expand our understanding of the natural history of high-grade prostatic intraepithelial neoplasia (HGPIN). This was a retrospective analysis in which they reviewed data from 74 consecutive patients with an initial diagnosis of HGPIN. The mean number of biopsies performed prior to the diagnosis of cancer was 5 (range: 3-13). The mean time to the diagnosis of cancer was 29 months (range: 7-83). Men with a history of HGPIN had a lower proportion of positive biopsies at the time of cancer diagnosis and smaller volume tumors on final pathology  compared to men with no history of HGPIN. The authors conclude that patients with an initial diagnosis of HGPIN on transrectal ultrasound (TRUS)-guided biopsy progressed to cancer at a mean of 29 months. The vast majority of patients that progressed to prostate cancer had low volume disease at the time of diagnosis and treatment. Our data indicate the importance of re-evaluation in HGPIN patients and suggest a trend toward low volume disease in carefully followed patients. The authors also suggest that a prospective study is needed to adequately define an evidence-based biopsy regimen in men with an initial biopsy result of HGPIN.

Prostate cancer patients believed to  be at intermediate or high risk for nodal metastases have historically undergone invasive diagnostic pelvic lymph-node dissection (PLND) as the gold standard diagnostic procedure for the detection of nodal disease. However, a new lymph-node-specific, magnetic resonance (MR)-contrast agent called ferumoxtran-10 (Combidex) can detect metastases in normal-sized nodes (< 8 mm in size) by use of MR lymphoangiography (MRL). Heesakkers et al. conducted a prospective, multicenter trial to compare the diagnostic accuracy of MRL with up-to-date multidetector computer tomography (MDCT), and test the hypothesis that a negative MRL finding can replace the need for a PLND. The study included 375 consecutive patients with prostate cancer at intermediate or high risk for lymph-node metastases. All patients were assessed by MDCT and MRL, and underwent PLND or fine-needle aspiration biopsy. The study was conducted at 11 hospitals in the Netherlands between April 8, 2003, and April 19, 2005. Results were as follows: 61 of 375 patients (16 percent) had lymph-node metastases. Sensitivity was 34 percent for MDCT and 82 percent for MRL. Specificity was 97 percent for MDCT and 93 percent for MRL. Positive predictive value (PPV) was 66 percent for MDCT and 69 percent for MRL. Negative predictive value (NPV) was 88 percent for MDCT and 96 percent for MRL. Of the 61 patients with lymph-node metastases, 50 were detected by MRL, of whom 40 (80 percent) had metastases in normal-sized lymph nodes. The high sensitivity and NPV of MRL imply that in patients with a negative MRL, the chance of positive lymph nodes is less than 11/302 (4 percent). The authors conclude that MRL had significantly higher sensitivity and NPV than MDCT for patients at intermediate or high risk for lymph-node metastases. They go on to state that, in such patients, after a negative MRL, the post-test probability of having lymph-node metastases is low enough to omit a PLND. [Editorial comment: It should be noted that ferumoxtran-10 (Combidex) is not approved for use as an MR contrast agent in Europe or in the USA. This agent has been in development for many years now.]

3 Responses

  1. The study of the Brazilian men reported tonight indicated that half considered the DRE “a source of shame.”

    Doesn’t this imply that anal intrusion is a cultural no-no in Brazilian society and elsewhere. Heck I can testify to how uncomfortable it made me feel for the decade plus I had an annual DRE during the 13 years before my prostatectomy. And the two biopsies I have had were not much more fun!

    So here’s my question: What are researchers doing to detect prostate cancer in a way that would not be anally invasive?

    Sounds like a facitious question, but I’m seriously wondering if anybody has given thought to this? I ask because we all know how hard it is to break down cultural barriers among men, to make sure they take the necessary steps to safeguard their own health.

  2. Dear Rabbi Ed: I believe you may have misinterpreted the data from this study.

    Of 450 men in the study, 8.2 percent (37 men) rejected DRE and, of those 37 men, 53.1 percent (20 men) stated that they did so because it was a “source of shame.” This is about 4.4 percent of the total study population. In other words, for > 95 percent of the study population, it was apparently NOT a sufficient source of shame for them NOT to have a DRE.

    This does not mean that any of us go around bragging about how many DREs we’ve had over the years.

    This also does not mean for one moment that we wouldn’t all prefer the existence of noninvasive, highly accurate, low-cost, diagnostic tests that could predict the presence and stage of prostate cancer with accuracy. I am sure we all would. And researchers have been searching for such tests for years, but to date they haven’t found any that meet the above criteria. In truth I find it hard to imagine any noninvasive test that would be able to tell a surgeon whether a specific area of the prostate felt “harder” to the touch or in some other way was able to inform about the risk for cancer at such a minimal cost as a physical examination. Have you ever observed a gynecological examination? We men are asked to put up with remarkably little when it comes to physical examinations. (Now turn you head and cough, please.)

  3. It’s depressing that the main determinant of PC treatment remains what type of clinician the patient sees and not necessarily what’s in his best interest. Practically speaking, everybody who is at risk, e.g., has a high PSA, is referred to a urologist — so why don’t 100% of men have surgery?

    There was an interesting review in Sunday Times of a book called “Nudge”, written by 2 economists. They are basically confirming what this article says. While we think we make free choices, we are almost always “nudged” in a certain direction — for example, we eat what’s put on our plate. Likewise, say the authors, most healthcare decisions are determined by the setting, i.e., what type of doctor is advising you.

    My question is, how can we “nudge” patients to see a more neutral PC specialist?

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