External Radiation for Prostate Cancer
Definitive Radiation Therapy External-Beam Treatment
Traditional radiation techniques encompass the entire prostate and, for those at high risk of the disease spreading, the pelvic lymph nodes. A recent study suggests that treating the lymph nodes may be beneficial in patients at risk for harboring lymph node metastases.
Conformal External-Beam Therapy
This type of therapy creates three-dimensional representations of target structures (ie, the prostate) and designs a high radiation dose that conforms to the target shape. The anatomic information used to define the target is generally derived from CT images obtained while the patient is placed in the precise treatment position.
Early results using conformal therapy showed an improvement in survival rates. Also, conformal therapy has permitted the use of doses far above traditional levels without significant increases in serious side effects.
Intensity-Modulated Radiotherapy (IMRT)
This type of treatment for prostate cancer has only recently been introduced. IMRT is a refinement of conformal external-beam therapy, employing a highly non-uniform beam to create greater conformal dose distributions. Although it is likely IMRT will have an increased benefit in the treatment of non-prostate cancers (for instance, head and neck cancers), there is emerging evidence that prostate cancer therapy is also an appropriate site for IMRT treatment.
Clinical studies are underway to determine the benefit of higher doses of external-beam therapy. At the present time, there is evidence to suggest a reduction in the number of patients who relapse.
High-Dose-Date (HDR) Devices
Besides permanent implants, which deliver low-dose-rate (LDR) radiotherapy, brachytherapy for prostate cancer has been delivered using temporary high-dose-rate devices, usually in patients with locally advanced disease. In this technique, a high dose (minimum, approximately 5 Gy) is delivered to the prostate over an hour by remotely inserting a highly radioactive source into catheters placed into the prostate under ultra-sound guidance while the patient is under anesthesia. Several treatments are given on separate occasions, and external-beam radiation is used for approximately five weeks as well.
The long-term consequences for normal tissue of delivering large doses per fraction using this technique are unclear. Also, long-term outcome data on tumor control are not yet available.
External Beam Radiation Treatment (EBRT)
with or without High Dose Radiation (HDR) interstitial therapy
For patients with locally extensive prostate cancer (Stage T3 - T6) the risk of cancer recurrence is high. This has prompted investigations into alternative means to intensify therapy.
One strategy has been to deliver large fractions of radiotherapy using HDR interstitial techniques in combination with external-beam radiation treatment. The large interstitial fractions deliver a high dose to the prostate but spare normal tissues, due to the rapid dose fall-off outside of the implanted volume. Early experience with this strategy is encouraging, but long-term data on outcome, particularly in patients with locally extensive disease, are still being compiled.
Patients with locally advanced prostate cancer probably are not good candidates for permanent prostate implants. Patients with stage T3-T4 tumors are at high risk of gross extra-prostatic involvement and this localized therapy may not offer adequate coverage of extra-prostatic disease.
Androgen Ablation + External Radiation Therapy
Recently, two potential benefits of the use of transient androgen ablation prior to external radiation have been identified. First, there may be some synergy between the apoptotic response induced by androgen deprivation and radiotherapy that may increase local control.
Second, androgen deprivation results in an average 20 percent decrease in prostate volume. This volume reduction not only may reduce the number of target cells, and thereby improve tumor control, but also may shrink the prostate and, thus, diminish the volume of rectum and bladder irradiated during conformal therapy. Complete androgen blockade can be achieved with the luteinizing hormone-releasing hormone (LHRH), (Lupron) or Zoladex plus flutamide (Eulexin), Casodex, or nilutamide(such as Anadron or Nilandron).
In addition, since metastases outside the prostate are the first manifestation of disease recurrence in many patients with prostate cancer, the use of early androgen deprivation may possibly delay, or even prevent, the development of metastatic disease.
Whether the combination of androgen ablation and radiation therapy affords a survival advantage in patients with locally advanced disease has not been definitively established. However, the results of recent investigations suggest that the combination may, in fact, have a survival benefit.
with or without adjuvant therapy
Radical prostatectomy is a surgical procedure which removes the entire prostate gland, as well as some surrounding tissue. It can be performed by creating a lower mid-line incision through the pubic area. This method allows for pelvic lymph node dissection. Some urologists prefer the perineal approach, which removes the prostate gland through an incision between the anus and the scrotum. The perineal requires a separate incision if lymph node removal is desired.
This is a reasonable option for patients with locally advanced prostate cancer. Stage T3 disease can be successfully treated with low morbidity and significant reductions in risk of local recurrence, with clinical over-staging. Well- and moderately differentiated cancers have cancer-specific survival rates of 30 to 76 percent at 10 years, comparable with that of other treatment outcomes. However, the risk of cancer recurrence after surgery for Stage T3-T4 cancer is substantial, and an adjuvant or secondary/salvage treatment will likely be required.
Treatment of Node-Positive Disease
Recent data from several U.S. centers have reported a survival benefit in men who undergo radical prostatectomy despite the presence of micro-metastases to regional pelvic lymph nodes. These men tend to do better and survive longer when started on early hormonal therapy, either with orchiectomy or an LHRH-agonist.
Whether any local treatment adds to overall survival in patients with known node involvement is debatable. This matter deserves further study. However, the addition of radiotherapy may be indicated in many situations, especially in young men.