BERKELEY, CA (UroToday.com) - Data from SWOG 8794 indicates that post-operative radiotherapy increases local control and overall survival in prostate cancer patients with high-risk features (extra-capsular extension, seminal vesicle involvement, positive surgical margins).(1-4)
Despite this benefit, a large percentage of patients relapse in long-term follow-up and the primary site of failure is local. (5) Inadequate radiation doses and poor target coverage are thought to explain these high rates of local recurrence.
During radical prostatectomy, malignant cells are shed in prostatic secretions. As a result, the entire surgical bed may contain microscopic malignant cells. Defining a target volume for radiotherapy in the post-operative setting is subjective in nature and complicated by changes in anatomy due to surgery and the limited information on the original pre-operative location of the prostate. Four consensus papers have been published defining guidelines for post-operative target coverage in prostate cancer (European Organisation for Research and Treatment of Cancer [EORTC], Faculty of Radiation Oncology Genito-Urinary Group [FROGG], Princess Margaret Hospital [PMH], and Radiation Therapy Oncology Group [RTOG]).(6-9) Although differences exist between these definitions, one common theme stressed by all is the importance of covering the entire pre-operative prostate bed and planes of surgical dissection as these are the areas considered to be the highest risk of containing microscopic disease.(10-12)
The ability of these guidelines to adequately cover the prostate bed has previously not been evaluated. We hypothesized that inadequate coverage of the prostate bed is a major factor contributing to relatively high rates of local failure with radiation in high-risk prostate cancer patients. The aim of our research was to evaluate the four guidelines in a cohort of patients treated with post-operative radiotherapy. We compared the radiotherapy coverage of each consensus definition to the pre-operative MRI defined prostate and gross visible tumour. We additionally assessed the role of incorporating pre-operative MRI into radiotherapy planning in the post-operative setting.
Our results showed that the four consensus guidelines did not completely cover the pre-operative location of the prostate as defined by MRI. The prostate base and mid-zones were the main sites of inadequate coverage. Moreover, regions of gross disease (tumour) identified on pre-operative MRI were also missed in the majority of cases.
These results validate our hypothesis that inadequate coverage of the prostate bed is likely a significant contributing factor to the relatively high rate of local failure following adjuvant and salvage radiotherapy. In order to further improve upon local control and overall survival in high-risk prostate cancer patients, strategies must be developed to increase the accuracy of radiotherapy planning. Incorporating pre-operative MRI into radiotherapy planning will permit more precise localization of the entire prostate bed and therefore ensure more accurate target coverage.
Prostate cancer patients with intermediate- or high-risk features planned for radical prostatectomy should be considered for pre-operative staging MRI of the pelvis. These patient subgroups are at increased risk of having extra-capsular extension, seminal vesicle involvement or positive surgical margins. We propose incorporating pre-operative imaging into post-operative radiotherapy planning as it increases accuracy of prostate bed definition. Based on our research, we have created a modified post-operative radiotherapy definition (Clinical Target Volume The Ottawa Hospital or CTV TOH) that incorporates pre-operative MRIs. CTV TOH should improve coverage of areas at highest risk of containing microscopic cancer cells and result in further improvements in local control and overall survival for patients with high risk prostate cancer.
References:
- Bolla M, van Poppel H, Collette L et al. Postoperative radiotherapy after radical prostatectomy: a randomised controlled trial (EORTC trial 22911).Lancet 2005;366(9485):572-8.
- Thompson IM Jr, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathologically advanced prostate cancer: a randomized clinical trial. JAMA 2006;296(19):2329-35.
- Wiegel T, Bottke D, Steiner U et al. Phase III postoperative adjuvant radiotherapy after radical prostatectomy compared with radical prostatectomy alone in pT3 prostate cancer with postoperative undetectable prostate-specific antigen: ARO 96-02/AUO AP 09/95. J Clin Oncol 2009;27:2924-2930.
- Thompson IM, Tangen CM, Paradelo J et al. Adjuvant radiotherapy for pathological T3N0M0 prostate cancer significantly reduces risk of metastases and improves survival: long-term followup of a randomized clinical trial. J Urol 2009181(3):956-62.
- Swanson GP, Hussey MA, Tangen CM et al. Predominant treatment failure in postprostatectomy patients is local: analysis of patterns of treatment failure in SWOG 8794. J Clin Oncol 2007;25(16):2225-9.
- Wiltshire KL, Brock KK, Haider MA et al. Anatomic boundaries of the clinical target volume (prostate bed) after radical prostatectomy. Int J Radiat Oncol Biol Phys 2007;69(4):1090-9.
- Sidhom MA, Kneebone AB, Lehman M et al. Post-prostatectomy radiation therapy: consensus guidelines of the Australian and New Zealand Radiation Oncology Genito-Urinary Group. Radiother Oncol 2008;88(1):10-9.
- Michalski JM, Lawton C, El Naqa I et al. Development of RTOG consensus guidelines for the definition of the clinical target volume for postoperative conformal radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 2010;76(2):361-8.
- Poortmans P, Bossi A, Vandeputte K et al. EORTC Radiation Oncology Group Guidelines for target volume definition in post-operative radiotherapy for prostate cancer, on behalf of the EORTC Radiation Oncology Group. Radiother Oncol 2007;84(2):121-7.
- Sella T, Schwartz LH, Swindle PW et al. Suspected local recurrence after radical prostatectomy: endorectal coil MR imaging. Radiology 2004;231(2):379-85.
- Kassabian VS, Bottles K, Weaver R et al. Possible mechanism for seeding of tumor during radical prostatectomy. J Urol 1993;150(4):1169-71.
- Connolly JA, Shinohara K, Presti JC Jr et al. Local recurrence after radical prostatectomy: characteristics in size, location, and relationship to prostate-specific antigen and surgical margins. Urology 1996 Feb;47(2):225-31.
Written by:
Jennifer Croke, MD and Shawn Malone, MD, FRCPC as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Postoperative radiotherapy in prostate cancer: The case of the missing target - Abstract
