Diethylstilboestrol (1 mg) in the management of castration-resistant prostate cancer.

OBJECTIVE: To investigate the efficacy of diethylstilboestrol (DES) in patients with advanced prostate cancer refractory to androgen suppression. METHODS: This retrospective study comprises 194 patients with prostate cancer treated with DES (1 mg daily) between 1976 and 2010. Study outcome parameters included demographic data, tumour characteristics, treatment history, prostate-specific antigen (PSA) responses, radiologic studies, adverse events and overall survival. RESULTS: At initiation of oestrogen therapy the mean patient age was 69 years (range: 48-89) and the median PSA was 96 ng/ml (range: 1.9-9,500). The median duration of prior prostate cancer treatment was 29 months (range: 1-365). DES was the second-line treatment in 58 patients and the third/fourth-line therapy in 136 men. A formal (≥50%) PSA response was observed in 95 patients (48.9%) and the median time to progression (TTP) was 250 days (95% CI, 180-360) for this group. An additional 62 patients (31.9%) had a partial PSA response with a median TTP of 150 days (95% CI, 92-180). Thirty-seven patients (19.1%) did not have a PSA response and the median TTP was 90 days (95% CI, 90-97). The median overall survival from the start of oestrogen therapy for the entire cohort was 576 days (95% CI, 482-690). The median overall survival of patients who had a formal (≥50%), partial (<50%) and no PSA response was 756 (95% CI, 670-1,429), 428 (95% CI, 340-630) and 329 (95% CI, 287-510) days, respectively. Thirty-nine patients (20.1%) were still alive at the end of the study. No treatment-related deaths occurred. CONCLUSIONS: In the age of chemotherapy this study highlights the efficacy of oestrogen therapy in castration-refractory prostate cancer. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

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.

Iatrogenic splenectomy during left nephrectomy: a single-institution experience of eight years.

INTRODUCTION: Iatrogenic injury to the spleen is not an uncommon complication. Left nephrectomy has been reported as the second commonest cause of iatrogenic splenectomy with a reported incidence between 1.3 and 24%. Iatrogenic splenectomy is associated with significant morbidity and mortality. AIMS: We reviewed the occurrence of iatrogenic splenectomy during left nephrectomy at our centre. Our aims were to determine the incidence of iatrogenic splenectomy within the Mid Yorkshire Hospitals NHS Trust in order to understand the nature of the splenic injury and the morbidity and mortality associated with it. METHODS: All splenectomy and nephrectomy histology reports from January 2000 to December 2007 were reviewed retrospectively. Indications for splenectomy and nephrectomy were identified. Patients' demographic data, tumour characteristics, operative details, length of hospital stay and any reported morbidity or mortality were collected. RESULTS: A total of 447 nephrectomies were identified which included 234 left nephrectomies. Within the same period 136 cases of splenectomy were performed. Thirty-four cases were iatrogenic splenectomies and 12 were caused by left nephrectomy. The incidence was 5.13%. The male to female ratio was 1:1 with an average age of 66 years. Grade 2 and stage pT2 renal cancer were the commonest tumour characteristics. All iatrogenic injuries occurred during mobilisation of the colon or division of adhesion. The average operative time was 4.7 h. Average length of hospital stay was 14 days. Five patients had postoperative complications and 1 died of respiratory failure and sepsis. CONCLUSION: Splenic injury during left nephrectomy is a morbid complication. A good understanding of anatomy and surgical approach may reduce the incidence, morbidity and mortality of iatrogenic splenectomy during left nephrectomy.

Fulguration of the lumen does not improve vasectomy sterilization rates.

OBJECTIVES: To assess the effect of adding lumen diathermy fulguration to our standard technique of vas ligation with polyglactin 910 (Vicryl(TM), Ethicon, Sommerville, NJ, USA) excision and fascial interposition, in an attempt to improve our sterilization rates. We previously reported the effect of changing suture material on vasectomy success rates; 3005 post-vasectomy semen analyses (PVSA) revealed a decrease in sterilization rates after surgery on changing from chromic catgut to polyglactin 910. PATIENTS AND METHODS: We retrospectively reviewed PVSA undertaken for vasectomies performed by urological surgeons at the Mid-Yorkshire NHS Trust for 18 months from September 2005 to February 2007. RESULTS: There were 592 vasectomies in all; the age distribution of patients between the groups treated with the standard and new method was similar. Overall, 166 patients (28%) failed to provide two semen samples as instructed, and so were excluded from further analyses. Sterility was achieved in 367 patients (86%); a further 28 (7%) have indeterminate analyses to date, with one of the last two PVSAs showing sperm, with the PVSA of 32 (7%) patients showing persisting sperm. For the eight surgeons reviewed the sterility rates were broadly similar. CONCLUSIONS: The introduction of diathermy fulguration of the lumen has not improved vasectomy sterilization rates, with up to 14% having sperm on PVSA.

Does the type of suture material used for ligation of the vas deferens affect vasectomy success?

OBJECTIVES: To determine retrospectively, the outcome of vasectomies performed by five urologists over a six year period in terms of achievement of azoospermia on post vasectomy semen analysis (PVSA) and to compare the effect of the type of suture material used for ligation of the vas deferens on the vasectomy success. METHODS: Review of PVSA results of 3005 consecutive vasectomies done in a district general hospital between November 1998 and October 2004. Patient records and vasectomy logs were reviewed and data analysed. The main outcome measure was achievement of azoospermia on PVSA. RESULTS: The age distribution of men between the two study groups was similar. Overall compliance to provide at least two semen samples for PVSA was 73.8% and was similar between the two groups. Failure to achieve azoospermia on PVSA was seen in 3.5% men (36/1038) in the chromic catgut group and 10.1% men (110/1088) in the Vicryl group (p < 0.0001). Also, the vasectomy failure rates for individual urologists increased significantly following introduction of Vicryl. CONCLUSIONS: In our study we noticed a three fold increase in failure to achieve azoospermia on PVSA with Vicryl as compared to chromic catgut. This study demonstrates that the type of suture material used for ligation of the vas deferens does affect the vasectomy success.

Using PSA to guide timing of androgen deprivation in patients with T0-4 N0-2 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 <2 ng/ml within the first year after immediate ADT were analyzed in 939 eligible patients randomly assigned to immediate (n=468) or deferred ADT (n=471). RESULTS: In both arms, patients with a baseline PSA>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 PSADT<12 mo were at increased risk to die from PCa and might have benefited from immediate ADT, whereas patients with a baseline PSA<50 ng/ml and a slow PSADT (>12 mo) were likely to die of causes unrelated to PCa, and thus could be spared the burden of immediate ADT.

Immediate or deferred androgen deprivation for patients with prostate cancer not suitable for local treatment with curative intent: European Organisation for Research and Treatment of Cancer (EORTC) Trial 30891.

PURPOSE: This study (EORTC 30891) attempted to demonstrate equivalent overall survival in patients with localized prostate cancer not suitable for local curative treatment treated with immediate or deferred androgen ablation. PATIENTS AND METHODS: We randomly assigned 985 patients with newly diagnosed prostate cancer T0-4 N0-2 M0 to receive androgen deprivation either immediately (n = 493) or on symptomatic disease progression or occurrence of serious complications (n = 492). RESULTS: Baseline characteristics were well balanced in the two groups. Median age was 73 years (range, 52 to 81). At a median follow-up of 7.8 years, 541 of 985 patients had died, mostly of prostate cancer (n = 193) or cardiovascular disease (n = 185). The overall survival hazard ratio was 1.25 (95% CI, 1.05 to 1.48; noninferiority P > .1) favoring immediate treatment, seemingly due to fewer deaths of nonprostatic cancer causes (P = .06). The time from randomization to progression of hormone refractory disease did not differ significantly, nor did prostate-cancer specific survival. The median time to the start of deferred treatment after study entry was 7 years. In this group 126 patients (25.6%) died without ever needing treatment (44% of the deaths in this arm). CONCLUSION: Immediate androgen deprivation resulted in a modest but statistically significant increase in overall survival but no significant difference in prostate cancer mortality or symptom-free survival. This must be weighed on an individual basis against the adverse effects of life-long androgen deprivation, which may be avoided in a substantial number of patients with a deferred treatment policy.