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Radiation therapy to the pelvic lymph nodes in high risk prostate cancer is required on several RTOG clinical trials. Based on a prior lymph node contouring project we have shown significant disagreement in the definition of pelvic lymph node volumes amongst GU radiation oncology specialists involved in developing and executing current RTOG trials.
A consensus meeting was held on October 3, 2007, to reach agreement on pelvic lymph node volumes. Data was presented to address the lymph node drainage of the prostate. Extensive discussion ensued to develop CTV pelvic lymph node consensus.
Consensus was obtained resulting in CT image-based pelvic lymph node CTVs. Based on this consensus the pelvic lymph node volumes to be irradiated include:
Lymph node CTVs include the vessels (artery and vein) and a 7mm radial margin being careful to “carve out” bowel, bladder, bone, and muscle. Volumes begin at the L5/S1 interspace and end at the superior aspect of the pubic bone. Consensus on DVH constraints for OARs were also attained.
Consensus on pelvic lymph node CTVs for radiation therapy to address high-risk prostate cancer was attained and is available as web-based CT images as well as a descriptive format through the RTOG. This will allow for uniformity in evaluating the benefit and risk of such treatment.
Pelvic lymph node (LN) radiation was a required part of the treatment for high-risk/locally advanced prostate cancer patients treated on all the prospective randomized trials used to establish the role of hormone therapy and radiation for this patient population. (1,2,3,4) In addition published data suggests that treating these volumes may improve outcomes for prostate cancer patients if the risk of lymph node involvement is significant.(5) Furthermore, there are two open Radiation Therapy Oncology Group (RTOG) trials for high risk prostate cancer patients which require pelvic lymph node radiation therapy.(6,7)
The challenge is that there are significant differences of opinion regarding appropriate pelvic LN volumes to be treated in this cohort of patients. A 2007 survey of RTOG genitourinary cancer experts indicated that significant variability existed amongst a group of radiation oncologists experienced in the treatment of prostate cancer and design of prostate cancer clinical trials.(8) Given the widely adopted use of intensity modulated radiation therapy (IMRT) to treat the pelvic lymph nodes and spare organs at risk (OAR) it is imperative that a consensus be obtained to establish the appropriate nodal volumes for these patients so that the relative safety and merit of such treatment can be established. The purpose of this study was to establish such a consensus.
Given the established variability in LN treatment volumes by the RTOG GU Radiation Oncologists a consensus meeting was held on October 3, 2007 sponsored by the RTOG. All physicians/institutions involved in the original contouring project were invited to attend. (8) Data was presented (CL) to address the lymph node drainage of the prostate using prostatic lymphography, extended lymph node dissection, the sentinel lymph node concept, anatomy texts, pelvic MRI imaging, and evaluation of pelvic lymph nodes treated on prior RTOG trials 85-31, 86-10, and 92-02 used to establish the role of hormone therapy and radiation for this high risk population.(1,2,3)
Consensus was obtained via the physicians present with extensive discussion and actual contouring on a CT scan used in the original contouring study.(8) Dose constraints for the organs at risk were also discussed with consensus participants polled regarding the dose constraints they commonly utilize and discussion ensued. Subsequent circulation of dose volume constraints and review of the CT image sets occurred following the meeting to refine the consensus volumes sand dose constraints for the OARs.
Data presented regarding prostatic lymphography(9,10) reveals prostatic lymph node drainage to the internal iliac, external iliac, presacral and common iliac nodes with the main drainage to the internal iliac and presacral lymph nodes.(9)
Extended lymph node dissection data, which generally involved resection of the external and internal iliac and obturator lymph nodes as well as the common and presacral lymph nodes, showed evidence of nodal drainage in multiple nodal sites.(11,12,13,14,15) Often the nodal involvement was not contiguous.(11,15) This data also pointed to the need to address nodes beyond the obturator and external iliac lymph nodes if one wishes to address all potentially involved areas with the presacral nodes as a significant area of node positivity.(11,14,15) Finally all the lymph node dissection data presented pointed to the fact that the more lymph nodes removed the more positive nodes found, and therefore, recommendation from this data was that patients with high risk prostate cancer should undergo extended lymph node dissection.(11–15) The message here is that the pelvic lymph nodes at risk include obturator, external and internal iliac, and presacral nodes.
Sentinel lymph node concept data shows that the process is not only feasible,(16,17,18) but the more recent data(18) reported (results on over 1,000 patients where extended lymph node dissection and positive sentinel lymph nodes) defined metastatic disease well beyond the obturator and external iliac regions alone. In this data there was evidence of lymph node metastasis to the presacral regions also.(18)
Basic anatomy data revealed three main drainage patterns for the prostate:
Pelvic MRI imaging with lymphotropic nanoparticles shows evidence of lymph node metastasis for advanced prostate cancer in the drainage areas of the common iliac, external and internal iliac, and presacral regions with an interesting lack of positive lymph nodes below the top of the pubic symphysis.(21) Similar MRI nanoparticle data from gynecologic malignancies shows evidence of lymph nodes well posterior to the external iliac vessels and well anterior the internal iliac vessels showing a need to include margins beyond the vessels themselves for adequate pelvic iliac lymph node coverage.(22) In addition this data suggested a minimum 7mm margin around the pelvic blood vessels to cover the involved lymph nodes.
In the interest of consistency in the definition of the pelvic LN regions for IMRT compared to prior techniques ,data from each of the RTOG trials (evaluating the role of hormone therapy and radiation for high risk patients) was reviewed. Previously a four-field box technique was used to address the pelvic lymph nodes.(1,2,3) (Fig 1) The upper border of this technique was at the L4/L5 or L5/S1 interspace and the lower border at the level of the bottom of the ischeal tuberosities. Laterally 2-cm lateral to the true pelvis was recommended. In the lateral fields the anterior border was to include the anterior aspect of the external iliac lymph nodes and the posterior border was to be posterior to the anterior boney sacrum so as to address the presacral lymph nodes superiorly and then to split the rectum inferiorly. These borders were chosen to be sure that the draining pelvic LNs were covered.
Review of all the data above and extensive discussions resulted in a consensus being obtained and contours performed on one of the CT scans used in the contouring project. (8) Special focus during the discussion had been placed on the importance of treating the presacral lymph nodes. Review of the data presented resulted in a recommendation to treat the presacral lymph nodes (subaortic only S1–S3). Figure 2 shows representative Clinical Target Volumes (CTV’s) contours drawn on the CT consensus scan. These contours were done by the consensus panel (all co-authors) and a written description was developed as follows:
Volume definition and dose constraints for organs at risk (OARs) were also discussed and resulted in a consensus for OAR guidelines. (Figure 3) The rectum should be empty at the time of simulation. Consistent with the RTOG definition of the rectum it is to be outlined from the sigmoid flexure to the bottom of the ischial tuberosities. The bladder should be comfortably full at the simulation. Two dose points were selected for both the rectum and bladder. These dose constraints were based on whole (solid) organ contours. No constraints were identified for the penile bulb and the iliac crests. Large bowel dose constraints were to be the same as the rectum. The small bowel dose limit was 52 Gy and the femoral heads <5 % of their volume at 50 Gy. Dose constraints for all OARs were based on the use of conventional fractionation using a dose per fraction of 1.8 to 2.0 Gy per day.
Adenocarcinoma of the prostate is the second most common cause of cancer death in US males with over 27,000 deaths estimated for 2007.(23) Many of these patients will have presented with locally advanced/high-risk disease where regional pelvic lymph node involvement is a reality. The role of radiation therapy in the cure of these patients is evolving, but certainly many can be controlled if not cured with the use of radiation and hormonal manipulation.(12,3,4) These cures are the result of the treatment to the pelvic lymph nodes and prostate in addition to systemic hormone therapy.(1,2,3,4) The exact role of the nodal radiation is still being evaluated yet it remains a requirement for two open RTOG trials, RTOG 05–21 looking at high risk patients and upfront treatment with radiation and hormone therapy plus or minus chemotherapy and for patients with recurrence after surgery (RTOG 05–34). With the advent of IMRT to treat the lymph nodes and spare OARs it becomes imperative that radiation oncologists treat the appropriate lymph node volumes or the relative merit and safety of such treatment can never be appropriately assessed.
Prior to this consensus it was clear that even RTOG GU “experts” did not agree on the lymph node CT volumes to be covered.(8) And other RTOG “experts” such as the gynecologic group have struggled with similar issues. (24) This consensus document is the result of extensive review of the literature to define the lymph nodes at risk, evaluation of lymph nodes treated on critically important recent trials for this high risk population and discussion to attain consensus on appropriate CTV lymph node volumes and dose constraint guidelines for OARs by leading GU radiation oncologists. This consensus document should serve as a guideline for radiation oncologists and is especially important for designing and conducting clinical trials. Utilizing these guidelines will ensure that patients who are at significant risk for pelvic lymph node metastasis and treated with radiation will have the correct lymph nodes addressed. In addition it will help to ensure the safety of such treatment if dose-volume histograms (DVH) suggested in these guidelines for the OARs are consistently followed. As with any set of treatment guidelines individual practioners will have to consider specific patient characteristics. Variability in anatomy and co-morbidities are factors which may need to be considered in specific cases. However, the guidelines presented in this consensus document will be useful to address the merit of pelvic lymph node radiation in high risk patients as it ensures that similar volumes are radiated and will help to avoid the “apples versus oranges” volumes that have existed prior to this consensus.(8)
Supported by grants from the National Cancer Institute, CA21661, CA32115, and CA37422.
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Conflict of Interest: None