Differences in Time to Disease Progression Do Not Predict for Cancer-specific Survival in Patients Receiving Immediate or Deferred Androgen-deprivation Therapy for Prostate Cancer: Final Results of EORTC Randomized Trial 30891 with 12 Years of Follow-up

BACKGROUND Trials assessing the benefit of immediate androgen-deprivation therapy (ADT) for treating prostate cancer (PCa) have often done so based on differences in detectable prostate-specific antigen (PSA) relapse or metastatic disease rates at a specific time after randomization. OBJECTIVE Based on the long-term results of European Organization for Research and Treatment of Cancer (EORTC) trial 30891, we questioned if differences in time to progression predict for survival differences. DESIGN, SETTING, AND PARTICIPANTS EORTC trial 30891 compared immediate ADT (n=492) with orchiectomy or luteinizing hormone-releasing hormone analog with deferred ADT (n=493) initiated upon symptomatic disease progression or life-threatening complications in randomly assigned T0-4 N0-2 M0 PCa patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Time to first objective progression (documented metastases, ureteric obstruction, not PSA rise) and time to objective castration-resistant progressive disease were compared as well as PCa mortality and overall survival. RESULTS AND LIMITATIONS After a median of 12.8 yr, 769 of the 985 patients had died (78%), 269 of PCa (27%). For patients receiving deferred ADT, the overall treatment time was 31% of that for patients on immediate ADT. Deferred ADT was significantly worse than immediate ADT for time to first objective disease progression (p<0.0001; 10-yr progression rates 42% vs 30%). However, time to objective castration-resistant disease after deferred ADT did not differ significantly (p=0.42) from that after immediate ADT. In addition, PCa mortality did not differ significantly, except in patients with aggressive PCa resulting in death within 3-5 yr after diagnosis. Deferred ADT was inferior to immediate ADT in terms of overall survival (hazard ratio: 1.21; 95% confidence interval, 1.05-1.39; p [noninferiority]=0.72, p [difference] = 0.0085). CONCLUSIONS This study shows that if hormonal manipulation is used at different times during the disease course, differences in time to first disease progression cannot predict differences in disease-specific survival. A deferred ADT policy may substantially reduce the time on treatment, but it is not suitable for patients with rapidly progressing disease

Letter to the Editor Re: Urs E. Studer, Laurence Collette, Peter Whelan, et al. Using PSA to guide timing of androgen deprivation in patients with TN-4 NO-2 M0 prostate cancer not suitable for local curative treatment (EORTC 30891).

OBJECTIVE: EORTC trial 30891 compared immediate versus deferred androgen-deprivation therapy (ADT) in T0-4 N0-2 M0 prostate cancer (PCa). Many patients randomly assigned to deferred ADT did not require ADT because they died before becoming symptomatic. The question arises whether serum prostate-specific antigen (PSA) levels may be used to decide when to initiate ADT in PCa not suitable for local curative treatment. METHODS: PSA data at baseline, PSA doubling time (PSADT) in patients receiving no ADT, and time to PSA relapse (>2 ng/ml) in patients whose PSA declined to 50 ng/ml were at a>3.5-fold higher risk to die of PCa than patients with a baseline PSA12 mo. Time to PSA relapse after response to immediate ADT correlated significantly with baseline PSA, suggesting that baseline PSA may also reflect disease aggressiveness. CONCLUSIONS: Patients with a baseline PSA>50 ng/ml and/or a PSADT12 mo) were likely to die of causes unrelated to PCa, and thus could be spared the burden of immediate ADT

Thermal spread of vessel-sealing devices evaluated in a clinically relevant in vitro model

Introduction: Bipolar vessel-sealing devices (VSDs) have advantages in urological surgeries (less hemorrhage, shorter operating time). However, these instruments can cause thermal injuries, which can result in neural damage and necrosis. The objectives of this study were to establish a reproducible in vitro model for standardized assessment of electrosurgical devices and to evaluate whether optimized placement of surgical instruments can reduce the thermal spread. Methods: We evaluated thermal spread of two VSDs in vitro using thin bovine muscle strips. Thermal injury was measured using an infrared camera, temperature probes and histology. The recordings were made with the VSD alone and with a rectangular clamp next to the VSD. Results: Both instruments showed a significant temperature spread of 2.5 mm lateral to the VSD. The placement of a metal clamp next to the VSD significantly reduced the temperature spread. Histological examinations were able to underline these findings. Conclusions: In this study we describe a straightforward clinically relevant in vitro model for the evaluation of future electrosurgical instruments. We demonstrated that the thermal spread of VSD could be further reduced by optimized placement of an additional surgical instrument. Our results could help surgeons protect sensitive structures like nerves in the vicinity of the VSD

Electrosurgery in urology: recent advances

Inadequate hemostasis is one of the most important causes of morbidity and mortality following urological surgery. Despite the long-term usage of coagulation, there is an ongoing development of new devices, including bipolar transurethral resection of the prostate or new vessel-sealing devices. A thorough understanding of the advantages and disadvantages of these new instruments can improve the operative experience for both the urologist and patient. The optimal coagulation system should be small, efficient, easy to handle and with low heat spread. In this article, we analyze different electrothermal coagulation systems and modern tissue-sealing devices in urological applications with the aim to substantiate the advantages and disadvantages of each technique in terms of efficacy and safety