EAU Guidelines on Prostate Cancer Aus, G.; Abbou, C.C.; Bolla, M. ...
European urology,
10/2005, Volume:
48, Issue:
4
Journal Article
Peer reviewed
The first summary of the European Association of Urology (EAU) guidelines on prostate cancer was published in 2001. These guidelines have been continuously updated since many important changes ...affecting the clinical management of patients with prostate cancer have occurred over the past years. The aim of this paper is to present a summary of the 2005 update of the EAU guidelines on prostate cancer.
A literature review of the new data has been performed by the working panel. The guidelines have been updated and level of evidence/grade of recommendation added to the text. This enables readers to better understand the quality of the data forming the basis of the recommendations.
A full version is available at the EAU Office or at
www.uroweb.org. Systemic prostate biopsies under ultrasound guidance is the preferred diagnostic method and the use of periprostatic injection of a local anaesthetic can significantly reduce pain/discomfort associated with the procedure. Active treatment (surgery or radiation) is mostly recommended for patients with localized disease and a long life expectancy with radical prostatectomy being the only treatment evaluated in a randomized controlled trial. Follow-up is at large based on prostate specific antigen (PSA) and a disease-specific history with imaging only indicated when symptoms occur. Cytotoxic therapy has become an option for selected patients with hormone refractory prostate cancer.
The knowledge in the field of prostate cancer is rapidly changing. These EAU guidelines on prostate cancer summarize the most recent findings and put them into clinical practice.
Milk fat globule-epidermal growth factor-factor VIII (MFGE8), also called lactadherin or SED1, is a secreted integrin-binding protein that promotes elimination of apoptotic cells by phagocytes ...leading to tolerogenic immune responses, and vascular endothelial growth factor (VEGF)-induced angiogenesis: two important processes for cancer development. Here, by transcriptomic analysis of 228 biopsies of bladder carcinomas, we observed overexpression of MFGE8 during tumor development, correlated with expression of genes involved in cell adhesion or migration and in immune responses, but not in VEGF-mediated angiogenesis. To test whether MFGE8 expression was instrumental in bladder tumor development, or a simple consequence of this development, we used genetic ablation in a mouse model of carcinogen-induced bladder carcinoma. We showed that Mfge8 was also upregulated in mouse carcinoma, and that in its absence, Mfge8-deficient animals developed less advanced tumors. Angiogenesis was similar in carcinogen-treated Mfge8-expressing or -deficient bladders, thus ruling out a major role of the proangiogenic function of Mfge8 for its protumoral role. By contrast, the tumor-promoting role of Mfge8 was not observed anymore in mice devoid of adaptive immune system, and human tumors overexpressing MFGE8 where invaded with macrophages and regulatory T cells, thus suggesting that MFGE8/lactadherin favors development of bladder tumors at least partly by an immune system-dependent mechanism. Our observations suggest future use of MFGE8-inhibiting molecules as therapies of bladder carcinomas, and of a limited number of other human cancers, in which our analysis of public databases also revealed overexpression of MFGE8.
Measuring health-related quality of life (QoL) after surgery is essential for decision making by patients, surgeons, and payers. The aim of this consensus conference was twofold. First, it was to ...determine for which diseases endoscopic surgery results in better postoperative QoL than open surgery. Second, it was to recommend QoL instruments for clinical research.
An expert panel selected 12 conditions in which QoL and endoscopic surgery are important. For each condition, studies comparing endoscopic and open surgery in terms of QoL were identified. The expert panel reached consensus on the relative benefits of endoscopic surgery and recommended generic and disease-specific QoL instruments for use in clinical research.
Randomized trials indicate that QoL improves earlier after endoscopic than open surgery for gastroesophageal reflux disease (GERD), cholecystolithiasis, colorectal cancer, inguinal hernia, obesity (gastric bypass), and uterine disorders that require hysterectomy. For spleen, prostate, malignant kidney, benign colorectal, and benign non-GERD esophageal diseases, evidence from nonrandomized trials supports the use of laparoscopic surgery. However, many studies failed to collect long-term results, used nonvalidated questionnaires, or measured QoL components only incompletely. The following QoL instruments can be recommended: for benign esophageal and gallbladder disease, the GIQLI or the QOLRAD together with SF-36 or the PGWB; for obesity surgery, the IWQOL-Lite with the SF-36; for colorectal cancer, the FACT-C or the EORTC QLQ-C30/CR38; for inguinal and renal surgery, the VAS for pain with the SF-36 (or the EORTC QLQ-C30 in case of malignancy); and after hysterectomy, the SF-36 together with an evaluation of urinary and sexual function.
Laparoscopic surgery provides better postoperative QoL in many clinical situations. Researchers would improve the quality of future studies by using validated QoL instruments such as those recommended here.
To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience.
Four thousand sixty-three patients from eight ...international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer UICC criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively.
Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001).
The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.
We recently identified activating mutations of fibroblast growth factor receptor 3 (FGFR3) in bladder carcinoma. In this study we assessed the incidence of
FGFR3 mutations in a series of 132 bladder ...carcinomas: 20 carcinoma
in situ (CIS), 50 pTa, 19 pT1, and 43 pT2–4. All 48 mutations identified were identical to the germinal activating mutations that cause thanatophoric dysplasia, a lethal form of dwarfism. The S249C mutation, found in 33 of the 48 mutated tumors, was the most common. The frequency of mutations was higher in pTa tumors (37 of 50, 74%) than in CIS (0 of 20, 0%;
P < 0.0001), pT1 (4 of 19, 21%;
P < 0.0001) and pT2–4 tumors (7 of 43, 16%;
P < 0.0001).
FGFR3 mutations were detected in 27 of 32 (84%) G1, 16 of 29 (55%) G2, and 5 of 71 (7%) G3 tumors. This association between
FGFR3 mutations and low grade was highly significant (
P < 0.0001).
FGFR3 is the first gene found to be mutated at a high frequency in pTa tumors. The absence of
FGFR3 mutations in CIS and the low frequency of
FGFR3 mutations in pT1 and pT2–4 tumors are consistent with the model of bladder tumor progression in which the most common precursor of pT1 and pT2–4 tumors is CIS.
To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an ...international multicenter study.
4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center.
The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients.
This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.
Authors from Naples, Paris and Rennes describe their efforts to develop a model for the preoperative prediction of outcome for non‐metastatic renal cancer. It is valuable to both urologist and ...patient to develop such a model, particularly so on preoperative criteria. The results of their study are interesting, leading to possibly helpful findings.
In another article, authors from Iceland estimated the risk of developing prostate and other cancer among relatives of men from that country diagnosed with prostate cancer. They found that a family history is a risk factor for prostate cancer, with the risk potentially higher for relatives of patients who died from the disease.
From the relative dearth of papers on quality of life after radical prostatectomy there are now several, and the authors from Bristol report on the effects of erectile dysfunction on quality of life after this type of treatment. They had a very high response rate (91%) to their questionnaire, and found that erectile dysfunction has a profound effect on quality of life. This finding is not a surprise, but do we need to examine our management of prostate cancer in the light of it?
OBJECTIVE
To develop a model to predict the outcome before surgery for non‐metastatic renal cell carcinoma (RCC).
PATIENTS AND METHODS
The records of 660 patients with non‐metastatic RCC, operated at three European medical institutes, were reviewed. Univariate and multivariate analyses were used to assess the clinical and pathological variables affecting disease‐free survival.
RESULTS
The median (range) follow‐up was 42 (2–180) months; the disease recurred in 110 patients (16%). The 2‐ and 5‐year overall survival was 87% and 54%, respectively. Five variables were significant in the univariate analysis, i.e. clinical presentation, clinical and pathological size, tumour grade and stage (P < 0.05). The preoperative variables, e.g. clinical presentation and clinical tumour size, were retained from the multivariate model. A recurrence risk formula (RRF) was constructed from this model, as (1.28 × presentation (asymptomatic = 0; symptomatic = 1) + (0.13 × clinical size)). Using this equation, the 2‐ and 5‐year disease‐free survival was 96% and 93% for an RRF of ≤ 1.2 and 83% and 68% for an RRF of > 1.2.
CONCLUSION
A formula was developed which, independent of stage, can be used to predict the rate of treatment failure in patients who undergo nephrectomy for non‐metastatic RCC. The RRF might be useful for more accurate sub‐grouping of good‐prognosis patients, and for counselling patients before surgery, their personalized follow‐up or adjuvant treatment once available.
We compared cancer specific survival of patients undergoing partial and radical nephrectomies for T1N0M0 renal tumors according to tumor size in a large multicenter series.
A retrospective analysis ...of 1,454 patients undergoing partial or radical nephrectomy for T1N0M0 renal tumors from 7 international academic centers was performed. Data were obtained for each patient including TNM stage (determined according to the 2002 TNM criteria), tumor size, type of surgery (partial versus radical nephrectomy) and cancer specific survival. Recurrence events were recorded when available.
Partial and radical nephrectomies were performed in 379 (26.1%) and 1,075 (73.9%) cases, respectively. Mean followup ± SD was 62.5 ± 51.8 months. Recurrence data were available on 544 patients. There were no significant differences in local or distant recurrence rates between patients undergoing partial or radical nephrectomy for either T1a (p = 0.6) or T1b tumors (p = 0.5). For patients with T1a tumors, there was no significant difference in the rate of cancer specific deaths between the partial (314) and radical (499) nephrectomy groups (2.2% versus 2.6%, respectively, p = 0.8). For patients with T1b tumors there was also no significant difference in the rate of cancer specific deaths between patients undergoing partial (65) and patients undergoing radical (576) nephrectomy (6.2% versus 9%, respectively, p = 0.6).
Partial nephrectomy is becoming the gold standard for renal tumors less than 4 cm but this treatment is much more controversial for larger T1 tumors. This large multicenter study suggests that it is safe to expand the indications of partial nephrectomy to include patients with T1N0M0 tumors up to 7 cm. However, careful patient selection remains necessary.
Purpose Open partial nephrectomy has emerged as the standard of care in the management of renal tumors smaller than 4 cm. While laparoscopic radical nephrectomy has been shown to be comparable to ...open radical nephrectomy with respect to long-term outcomes, important questions remain unanswered regarding the oncological efficacy of laparoscopic partial nephrectomy. We examined the practice patterns and pathological outcomes following laparoscopic partial nephrectomy. Materials and Methods A survey was sent to academic medical centers in the United States and in Europe performing laparoscopic partial nephrectomy. The total number of laparoscopic partial nephrectomies, positive margins, indications for intraoperative frozen biopsy as well as tumor size and position were queried. Results Surveys suitable for analysis were received from 17 centers with a total of 855 laparoscopic partial nephrectomy cases. Mean tumor size was 2.7 cm (±0.6). There were 21 cases with positive margins on final pathology, giving an overall positive margin rate of 2.4%. Intraoperative frozen sections were performed selectively at 10 centers based on clinical suspicion of positive margins on excised tumor. Random biopsies were routinely performed on the resection bed at 5 centers. Frozen sections were never performed at 2 centers. Of the 21 cases with positive margins 14 underwent immediate radical nephrectomy based on the frozen section and 7 were followed expectantly. Conclusions Early experience with laparoscopic partial nephrectomy in this multicenter study demonstrates oncological efficacy comparable to that of open partial nephrectomy with respect to the incidence of positive margins. The practice of intraoperative frozen sections varied among centers and is not definitive in guiding the optimal surgical treatment.
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