K. Vekemans

Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911)

BACKGROUND Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We did a randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation with prostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. METHODS After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-see policy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks). Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positive surgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-free survival. Analysis was by intention to treat. FINDINGS The median age was 65 years (IQR 61-69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74.0%, 98% CI 68.7-79.3 vs 52.6%, 46.6-58.5; p<0.0001). Clinical progression-free survival was also significantly improved (p=0.0009). The cumulative rate of locoregional failure was significantly lower in the irradiated group (p<0.0001). Grade 2 or 3 late effects were significantly more frequent in the postoperative irradiation group (p=0.0005), but severe toxic toxicity (grade 3 or higher) were rare, with a 5-year rate of 2.6% in the wait-and-see group and 4.2% in the postoperative irradiation group (p=0.0726). INTERPRETATION Immediate external irradiation after radical prostatectomy improves biochemical progression-free survival and local control in patients with positive surgical margins or pT3 prostate cancer who are at high risk of progression. Further follow-up is needed to assess the effect on overall survival.

Identification of Patients With Prostate Cancer Who Benefit From Immediate Postoperative Radiotherapy: EORTC 22911

PURPOSE The randomized controlled European Organisation for Research and Treatment of Cancer (EORTC) trial 22911 studied the effect of radiotherapy after prostatectomy in patients with adverse risk factors. Review pathology data of specimens from participants in this trial were analyzed to identify which factors predict increased benefit from adjuvant radiotherapy. PATIENTS AND METHODS After prostatectomy, 1,005 patients with stage pT3 and/or positive surgical margins were randomly assigned to a wait-and-see (n = 503) and an adjuvant radiotherapy (60 Gy conventional irradiation) arm (n = 502). Pathologic review data were available for 552 patients from 11 participating centers. The interaction between the review pathology characteristics and treatment benefit was assessed by log-rank test for heterogeneity (P < .05). RESULTS Margin status assessed by review pathology was the strongest predictor of prolonged biochemical disease-free survival with immediate postoperative radiotherapy (heterogeneity, P < .01): by year 5, immediate postoperative irradiation could prevent 291 events/1,000 patients with positive margins versus 88 events/1,000 patients with negative margins. The hazard ratio for immediate irradiation was 0.38 (95% CI, 0.26 to 0.54) and 0.88 (95% CI, 0.53 to 1.46) in the groups with positive and negative margins, respectively. We could not identify a significant impact of the positive margin localization. CONCLUSION Provided careful pathology of the prostatectomy is performed, our results suggest that immediate postoperative radiotherapy might not be recommended for prostate cancer patients with negative surgical margins. These findings require validation on an independent data set.

Postoperative Radiotherapy After Radical Prostatectomy: A Randomised Controlled Trial (EORTC Trial 22911)

Summary Background Local failure after prostatectomy can arise in patients with cancer extending beyond the capsule. We dida randomised controlled trial to compare radical prostatectomy followed by immediate external irradiation withprostatectomy alone for patients with positive surgical margin or pT3 prostate cancer. Methods After undergoing radical retropubic prostatectomy, 503 patients were randomly assigned to a wait-and-seepolicy, and 502 to immediate postoperative radiotherapy (60 Gy conventional irradiation delivered over 6 weeks).Eligible patients had pN0M0 tumours and one or more pathological risk factors: capsule perforation, positivesurgical margins, invasion of seminal vesicles. Our revised primary endpoint was biochemical progression-freesurvival. Analysis was by intention to treat. Findings The median age was 65 years (IQR 61–69). After a median follow-up of 5 years, biochemical progression-free survival was significantly improved in the irradiated group (74·0%, 98% CI 68·7–79·3

Impact of pathology review of stage and margin status of radical prostatectomy specimens (EORTC trial 22911)

Pathological staging and surgical margin status of radical prostatectomy specimens are next to grading the most important prognosticators for recurrence. A central review of pathological stage and surgical margin status was performed on a series of 552 radical prostatectomy specimens of patients, participating in the European Organisation for Research and Treatment of Cancer trial 22911. Inclusion criteria of the trial were pathological stage pT3 and/or positive surgical margin at local pathology. All specimens were totally embedded. Data of the central review were compared with those of local pathologists and related to clinical follow-up. Although a high concordance between review pathology and local pathologists existed for seminal vesicle invasion (94%, κ=0.83), agreement was much less for extraprostatic extension (57.5%, κ=0.33) and for surgical margin status (69.4%, κ=0.45). Review pathology of surgical margin status was a stronger predictor of biochemical progression-free survival in univariate analysis [hazard ratio (HR)=2.16 and p=0.0002] than local pathology (HR=1.08 and p>0.1). The review pathology demonstrated a significant difference between those with and without extraprostatic extension (HR=1.83 and p=0.0017), while local pathology failed to do so (HR=1.05 and p>0.8). The observations suggest that review of pathological stage and surgical margin of radical prostatectomy strongly improves their prognostic impact in multiinstitutional studies or trials.

A multi-institutional analysis comparing adjuvant and salvage radiation therapy for high-risk prostate cancer patients with undetectable PSA after prostatectomy.

BACKGROUND AND PURPOSE In men with adverse pathology at the time of radical prostatectomy (RP), the most appropriate timing to administer radiotherapy (RT) remains a subject for debate. To determine whether salvage radiotherapy (SRT) upon early prostate-specific antigen (PSA) relapse is equivalent to immediate adjuvant radiotherapy (ART) post RP. MATERIAL AND METHODS 130 patients receiving ART and 89 receiving SRT were identified. All had an undetectable PSA after RP. Homogeneous subgroups were built based on the status (±) of lymphatic invasion (LVI) and surgical margins (SM), to allow a comparison of ART and SRT. Biochemical disease-free survival (bDFS) was calculated from the date of surgery and from the end of RT. The multivariate analysis was performed using the Cox Proportional hazard model. RESULTS In the SM-/LVI- and SM+/LVI- groups, SRT was a significant predictor of a decreased bDFS from the date of surgery, while in the SM+/LVI+ group, there was a trend towards significance. From the end of RT, SRT was also a significant predictor of a decreased bDFS in three patient groups: SM-/LVI-, SM+/LVI- and SM+/LVI+. Gleason score >7 showed to be another factor on multivariate analysis associated with decreased bDFS in the SM-/LVI- group, from the date of surgery and end of RT. Preoperative PSA was a significant predictor in the SM-/LVI- group from the date of RP only. CONCLUSIONS Immediate ART post RP for patients with high risk features in the prostatectomy specimen significantly reduces bDFS after RP compared with early SRT upon PSA relapse.

Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium

BackgroundIn Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8%). Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. This suggests that selenium may also be suitable for chemoprevention of recurrence.MethodThe SELEBLAT study opened in September 2009 and is still recruiting all patients with non-invasive transitional cell carcinoma of the bladder on TURB operation in 15 Belgian hospitals. Recruitment progress can be monitored live at http://www.seleblat.org Patients are randomly assigned to selenium yeast (200 μg/day) supplementation for 3 years or matching placebo, in addition to standard care. The objective is to determine the effect of selenium on the recurrence of bladder cancer. Randomization is stratified by treatment centre. A computerized algorithm randomly assigns the patients to a treatment arm. All study personnel and participants are blinded to treatment assignment for the duration of the study.DesignThe SELEnium and BLAdder cancer Trial (SELEBLAT) is a phase III randomized, placebo-controlled, academic, double-blind superior trial.DiscussionThis is the first report on a selenium randomized trial in bladder cancer patients.Trial registrationClinicalTrials.gov identifier: NCT00729287

Clinical evaluation of 99mTc-DMSA renogram

Two hundred-two 99mTc-DMSA renograms for urologic problems were evaluated. Some technical aspects of the examination and the value of the scintigraphic depth estimation are discussed. Pre- and postoperative uptake values in patients with renal surgery and sequential postoperative examinations are considered. The value of DMSA renograms in predicting recovery in obstructive uropathy and in deciding to opt for conservative therapy or nephrectomy is discussed.

Phase III randomised chemoprevention study of Selenium on the recurrence of non-invasive bladder cancer. The SELEnium and BLAdder cancer Trial (SELEBLAT)

Background In Belgium, bladder cancer is the fifth most common cancer in males (5.2%) and the sixth most frequent cause of death from cancer in males (3.8 %). The per-patient lifetime cost is the highest of all other types of cancer. Previous epidemiological studies have consistently reported that selenium concentrations were inversely associated with the risk of bladder cancer. We therefore hypothesized that selenium may also be suitable for chemoprevention of recurrence.