Does Pelvic Irradiation Play a Role in the Management of Prostate Cancer?

The article by Stock et al does an excellent job of outlining the controversies surrounding the use of elective pelvic lymph node irradiation in the management of prostate cancer. It points out the dramatic change in the current incidence of lymph node metastasis, due, in part, to screening and early detection strategies. In addition, the authors very adequately summarize both the literature on the use of radiation for lymph node-positive disease and the data on pelvic vs nonpelvic irrad-iation. However, as outlined in the literature, the prognosis for patients with node-positive disease remains poor, with subsequent dissemination of prostate cancer common and elective lymph node irradiation dem-onstrating no beneficial effect to date.

In view of these data, which therapeutic path should a physician choose when faced with a patient at risk for pelvic lymph node involvement? The issues surrounding the benefits of whole-pelvic irradiation have been discussed and debated for nearly 20 years. Some claim that part of the benefit of elective lymph node irradiation comes from superior coverage of the primary tumor, as compared to the historically inadequate coverage achieved with the use of pre-computed tomography (CT) or nonconformal-based field design. In elective lymph node irradiation, the prostate would be adequately incor-porated within the pelvic volume and, therefore, would be relatively underdosed for only that portion of treatment during which the pelvic lymph nodes are excluded.

Toxicity and Dose Escalation

However, in the era of CT scan-based conformal irradiation, this secondary benefit of elective pelvic lymph node irradiation is almost certainly unnecessary and may, in fact, be harmful, although such harm is certainly not demonstrated in most of the current randomized studies comparing patients who do and do not receive elective pelvic irradiation. These studies suggest, as is noted in the article by Stock et al, that the risk of chronic morbidity is not increased by the use of pelvic irradiation. One important consideration, however, is that all of these patients received relatively standard doses of irradiation in the range of 6,500 to 7,000 cGy.

The current trend toward dose escalation through the use of conformal design and delivery of radiation may negate the relative safety of pelvic lymph node irradiation. Hanks et al demonstrated a significant rise in the rate of rectal complications when radiation doses were elevated to the 7,800-cGy level. These patients did, however, have some radiation delivered to a wider, low-pelvic field. In addition, in the Wayne State University experience with both hyperfractionated photon dose escal-ation and neutron dose escalation, the exclusion of pelvic lymph node irradiation significantly lowered the rate of chronic morbidity to the bladder and rectum.

Choosing a Treatment Path

Thus, it would seem that radiation oncologists have a choice to make. The choice is either to attempt to give higher doses of radiation in order to increase the probability of tumor control in patients with nonmetastatic prostate cancer, or to include the pelvic lymph nodes so as to try to achieve long-term control in patients with occult metastatic disease in the pelvic lymphatics. Until data are available to support or refute the benefit of either of these approaches, we have adopted the policy of trying to increase the dose and improve the outcome of local treatments, rather than depending on local and regional treatments to prevent consequent dissemination of the tumor. Thus, we have eliminated the use of elective pelvic lymph node irradiation in favor of routine use of dose escalation and ongoing study of the maximum tolerated dose of radiation to the prostate.

What to do with the patient with known metastatic disease in the pelvic lymph nodes is also a thorny and difficult issue, however. Most of the data suggest that the probability of patients being alive and free of disease 10 years following local or regional treatment is extremely low. More important, however, is the issue of whether the patients who are alive, with or without disease, are alive as a consequence of that regional treatment rather than in spite of it. Until recently, there were few data to suggest that the addition of regional treatment to patients with early metastatic disease has an impact on survival. In fact, a current study by the Radiation Therapy Oncology Group (RTOG) in which patients with lymph node-positive disease are randomized to hormones alone vs hormones plus radiation therapy should answer this question.

New Data Supporting Postoperative Irradiation

The recent published experience in breast cancer suggesting that the addition of postoperative irradiation in lymph node-positive disease led to a small but statistically significant improvement in survival adds credence to the potential benefit of regional treatment in node-positive prostate cancer patients. However, the decision of how much risk to take in patients in whom the mainstay of treatment is systemic therapy must be individualized, based on the health and life expectancy of each patient. After 20 years of clinical empiricism in small-scale trials, only large clinical trials can yield definitive information that would allow us to make decisions regarding the management of this group of patients.