What is the evidence that surgery improves the outcomes in men with locally advanced disease?
Surgery for men with locally advanced disease has been rarely reported in the literature. Where it has been performed it has frequently been accompanied by ADT and it has been difficult to separate the effect of the ADT from surgery. It has been possible to identify three randomised studies published prior to 2006 of surgical interventions for the treatment of prostate cancer that included patients with locally advanced disease.
In 1994 Isaka et al reported a randomised trial comparing radical prostatectomy and external beam radiotherapy for men with stage B2 and C disease. Both arms had neoadjuvant and adjuvant endocrine therapy. The follow-up of 100 patients entered was very short, an average of 25 months. There was only one cancer death and no conclusions could be drawn.
Akakura et al 1999 published an update of the 1994 study. The follow-up was still relatively short at a median of 58.5 months and given the trial design, it was not possible to isolate the effect of ADT on patient survival. However, the progression-free and cause-specific survival at five years was superiorfor surgery, suggesting that surgery may have provided some benefit over sub-optimal-dose radiotherapy using old techniques. Patients treated with surgery had significantly higher incontinence rates and lower long-term urinary difficulty and gastrointestinal toxicity rates compared to those treated with radiotherapy.
In a more recent update of this trial with a median follow-up of 102 months, surgery was associated with better survival and progression outcomes however none of these benefits were statistically significant.
Biochemical progression-free survival rates for the surgery and radiotherapy groups were 76.2% versus 71.1% respectively. Thus biochemical progression-free rates were better in the surgery group, as were the clinical progression-free rates of 83.5% versus 66.1%, and the cause-specific survival rates of 85.7% versus 77.1%. The overall survival rates were 67.9% versus 60.9%. There was a significantly higher incontinence rate in the surgery group, but no other significant difference in toxicity was reported.
In 2003 Clark et a reported a total of 123 patients who were randomised to an extended node dissection on the right side and a limited dissection on the left. However, only nine patients were T2b or T3 and no long-term survival was reported.
Thomas et al 1992 in a small study randomised men with T3 or T4 prostate cancer and urinary retention to transurethral resection of the prostate and orchidectomy, or orchidectomy alone. On the basis of the outcomes of the study, the authors recommended, because of the morbidity associated with the transurethral resection group, that surgery should take place only if the men failed to void after the initial orchidectomy.
Further appropriately designed randomised trials should be undertaken to determine whether surgery has a significant role in the management of men with locally advanced prostate cancer, other than to relieve urinary outlet obstruction in conjunction with androgen deprivation therapy.
Evidence summary and recommendations
| For the treatment of locally advanced disease there are no RCTs comparing surgery with modern higher-dose radiotherapy or ADT.
For locally advanced disease there are no RCTs examining the efficacy of extended lymph node dissection compared with standard lymph node dissection.
In one small RCT for men with urinary retention the addition of TURP to orchidectomy resulted in increased morbidity
|There is insufficient evidence to support the use of surgery in the management of advanced prostate cancer, with the possible exception of a transurethral resection of the prostate in men who are unable to void after androgen deprivation therapy.||C|
- Isaka S, Shimazaki J, Akimoto S, Okada K, Yoshida O, Arai Y, et al. A prospective randomized trial for treating stages B2 and C prostate cancer: radical surgery or irradiation with neoadjuvant endocrine therapy. Jpn J Clin Oncol 1994 Aug;24(4):218-23 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8072201.
- Akakura K, Isaka S, Akimoto S, Ito H, Okada K, Hachiya T, et al. Long-term results of a randomized trial for the treatment of Stages B2 and C prostate cancer: radical prostatectomy versus external beam radiation therapy with a common endocrine therapy in both modalities. Urology 1999 Aug;54(2):313-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10443731.
- Akakura K, Suzuki H, Ichikawa T, Fujimoto H, Maeda O, et al. A randomized trial comparing radical prostatectomy plus endocrine therapy versus external beam radiotherapy plus endocrine therapy for locally advanced prostate cancer: results at median follow-up of 102 months. Japanese Study Group for Locally Advanced Prostate Cancer,. Jpn J Clin Oncol 2006 Dec;36(12):789-93 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/17082219.
- Clark T, Parekh DJ, Cookson MS, Chang SS, Smith ER Jr, Wells N, et al. Randomized prospective evaluation of extended versus limited lymph node dissection in patients with clinically localized prostate cancer. J Urol 2003 Jan;169(1):145-7; discussion 147-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12478123.
- Thomas DJ, Balaji VJ, Coptcoat MJ, Abercrombie GF. Acute urinary retention secondary to carcinoma of the prostate. Is initial channel TURP beneficial? J R Soc Med 1992 Jun;85(6):318-9 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/1625259.