Highlights of the 2007
European Association of Urology Congress
An Overview by Douglas Chinn, MD
Reprinted from PCRI Insights August, 2007 v 10.3

The 22nd Annual European Association of Urology Congress, held in Berlin In March this year, turned out to be the largest EAU meeting ever. There were over 12,000 participants, representing 113 different countries. This fact emphasizes that this is no longer simply a European conference, but rather has truly become international.

Once again, PC was extensively covered, albeit somewhat differently. Last year’s meeting had an excellent overview of PC with speakers emphasizing the aspect of variable outcome data (1) that can be confounding to patients and physicians alike, and (2) that diagnosis does not necessarily translate into treatment. What I felt this year was a lack of impartial presentations, and a sense that last year’s lessons had been somewhat forgotten. However, the meeting itself again maintained an open mind to new ideas and technology. The focus for PC this year was on quality of life, which included Active Surveillance, screening markers, robotic surgery, cryosurgery, and HIFU. Included were discussions and presentations on new and novel diagnostic screening and imaging technology.

There is good reason for so much focus on PC. The Congress pointed out that, worldwide, there were 670,000 new cases of prostate cancer diagnosed last year, 225,000 of them in Europe. It was clear from multiple presentations that regardless of the therapy, low- and moderate-risk patients benefit the most and high-risk patients the least with interventional therapy for PC. Also, there are some who suggest that there are patients who can avoid any intervention. Why does this matter at all? Because all therapies have side effects, and the goal is to minimize the invasiveness and side effects while maintaining the curative intent.

Active Surveillance

I felt that this was the dominating theme of the EAU for PC. An excellent keynote discussion was presented by Prof. Abrahamsson of Malmo, Sweden. With the advent of PSA screening in Europe, there has been a dramatic increase in the diagnosis of low- and moderate-risk group patients. Furthermore, in the 8.2-year follow-up of the Scandinavian Prostatic Cancer Group Study, definitive therapy has demonstrated an advantage over watchful waiting in terms of overall survival, PC mortality, and distant metastases. However, the problem remains: Who may benefit from watchful waiting, and how is that determined? This important paradigm shift has created the concept of active surveillance, in which therapeutic intervention is planned in the event that any early evidence of disease progression is detected.

Why is active surveillance being discussed at all? Because despite what some published data presents, it is clear that no definitive therapy is without risks and complications that affect quality of life, especially incontinence and to a somewhat lesser extent, impotence or erectile dysfunction. Active surveillance is based upon individualized therapy, as opposed to a one-size-fits-all attitude. The ideal candidates must be in the low-risk group (with a low PSA, Gleason Score and biopsy tumor volume T2a). The major problem is accurately determining who these patients are, and the information (presented later in this article) on PCA3 and dynamic contrast enhanced 3T MRI (DCE 3T MRI) may be able to help provide the answers in the future. Prof. Abrahamsson made his position clear that younger patients should be treated and that older, low-risk patients may be better suited by active surveillance.

Currently, there are no standardized guidelines for active surveillance protocol, but trials are underway. PSA velocity is an important parameter, which should be closely monitored and prostate biopsies should also be repeated. My current protocol is a PSA test every three months, a repeat biopsy at least six months after the first one, and a repeat biopsy annually thereafter. For patients in whom subsequent biopsies are negative, I may follow only with color Doppler ultrasound every six months, and, if all other parameters remain unchanged, perhaps a rebiopsy 2-4 years later. This is where I believe that PCA3 may be able to provide a crucial role in this process.

PCA3

Prof. J Schalken of Nijmegen, The Netherlands, lectured on PCA3, a test that may help refine the screening process. A genetic marker specifically designed for PC cells, PCA3 directly detects PC from the urine. It is based upon the concept that PC cells are excreted into the ducts by the prostate massage and then washed out with the urine. The test itself is straightforward; the patient is given a DRE/prostate massage and then voids into a container.

How good is this test? Two important studies have been conducted, one in the US and one in European. In both studies, patients who had elevated PSAs and a negative first biopsy underwent a PCA3 test, and the results were compared to those of follow-up biopsies. The US study involved 233 patients. Of those who had positive PCA3s, 27% were found to have cancer on a second biopsy. In the 199-patient European study, 25% had a positive second biopsy. As shown in Figure 1, the sensitivity for the two studies were 58% and 57%, respectively, and the specificity was virtually identical (72% vs. 73%). The conclusion was that the higher the PCA3 score, the greater the chance that the cancer is significant. Conversely, a low PCA3 score predicts a tumor volume <0.5cc and a Gleason Score < 6.

Currently, PCA3 is recommended for an elevated PSA with a negative biopsy. However, one might consider the diagnostic sequence of PSA test, then a PCA3 test, which would be followed by a biopsy if the PCA3 is positive. Perhaps a rise in PCA3 may also be useful in determining when best to switch from active surveillance to treatment. In summary (see Figure 2), PCA3 is highly specific to PC and unlike serum PSA is not falsely elevated by benign conditions, including BPH, prostatitis, DRE, bicycle riding, or sexual activity. PCA3 is currently available in the United States, from OURLab, Molecular Profiling Institute, and Bostwick Labs.

Robotic Radical Prostatectomy

Professor Manfred Wirth presented a podium discussion on the growth demand for robotic radical prostatectomy (RP). There are more than 800 robotic systems installed world wide. In 2004, 8000 da Vinci radicals were performed, and 33,000 were performed in 2006. The most recent data does demonstrate the advantages of such a minimally invasive procedure: less blood loss, shorter hospital stay, less pain, quicker recovery, and perhaps less incontinence and impotency. However, the increased use of the da Vinci has not decreased the age-old problem of finding positive margins (extracapsular extension or ECE) and involved lymph nodes after the prostate is removed.

Imaging Modalities for Local Extension

Accurately determining tumor volume and location enables us to more accurately decide on therapy: active surveillance, focal therapy, subtotal gland ablation, or total gland therapy including RP. However, it is generally accepted that prostate biopsies are not very accurate in assessing the true volume and location of cancer in the prostate gland. Saturation biopsies are the closest test that we have, short of an RP specimen. The risk for positive surgical margins (ECE) or seminal vesicle (SV) involvement at the time of RP ranges anywhere from 6-25%. If the actual risk is known preoperatively, then perhaps surgery can be avoided. There were several innovative imaging technologies presented in abstract form.

Dynamic Enhanced 3 T MRI Scanning

B. Zelhof, et al., from University of Hull, Centre of MR Investigations, Hull, UK, presented a study in which 52 patients were scanned prior to RP, and the imaging accuracy was compared with the pathologic surgical specimen for ECE or SV involvement. “Higher signal intensity leads to an increase in spatial and temporal resolution of the MR measurements, compared with standard magnetic strength at 1.5T,” he reported. The study found a 92% accuracy and 97% specificity correlation for ECE when compared with RP specimens. I know of only one site in the U.S. (The Diagnostic Center for Diseases in Florida) where this scan is available.

Standard vs. Extended Pelvic Lymph Node Dissection

Another hot topic of discussion at the EAU involved the lymph node status of patients prior to RP that addressed the question: “who and how do we treat?” The problem is that RP is a curative intent, but if the lymph nodes are involved with cancer, what is the risk to benefit ratio of RP? The obvious answer is to diagnose lymph node involvement prior to treatment. However, there is still no radiologic study with high sensitivity and specificity. The use of 11C-Choline PET Scan appears promising, but 11C-Choline has not yet been approved by the FDA for use with PET scanners in the U.S.

The debate then centers on how extensive should the lymph node dissection be at the time of the RP. The current standard is a limited pelvic node dissection. Several studies demonstrated that the extensive node dissections (>30 lymph nodes removed) had a higher cancer detection rate (30%). However, the risks and complications of extensive lymph node dissection were not discussed. The current recommendations for an extended pelvic node dissection are PSA > 10, a T2c clinical stage, and a Gleason score > 6 (i.e. high-risk patients). However, important questions not addressed were: (1) What happens to the patient after such large number of positive nodes are found and (2) Was the surgery of any benefit? This reinforces the glaring deficiency that exists for accurate staging of high risk PC and avoiding unnecessary surgery.

Cryosurgery and HIFU

Finally, what was the biggest surprise of the meeting? Last year and again this year, Professor Gunner Aus of Göteborg, Sweden in a podium session reviewed data on newer minimally invasive alternatives to RP, namely cryosurgery and HIFU. At the 2006 EAU Congress, Prof. Aus strongly expressed his opinion that both technologies should be considered experimental. And he expressed the same feelings for cryosurgery this year. However, I was totally surprised to hear him issue a strong confirmation that HIFU should no longer be considered experimental, and should be considered as a treatment option. He clearly stated that this was based upon the most recent published data from Lyon, Munich and Regensburg.

Final Thoughts

This is what impresses me most about the EAU each year, that the thought leaders remain open-minded and progressive. This in turn benefits science and ultimately our patients. Next year, the EAU convenes in Milan, and this reporter hopes to be able to gain insights and provide updates on next year’s new ideas and advances in our war with prostate cancer.

Prostate Cancer Research Institute (PCRI)
 

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