Commentary: High Risk

Notes for Commentary: High Risk: While the observations on the interactive graph are pertinent to the results of treatment, an individual decision for a particular treatment can be influenced by multiple factors. We strongly encourage scheduling consultations with Prostate Cancer Doctors specializing in the fields of Surgery, Brachytherapy and Radiation Oncology. Discussions with an expert in Medical Oncology can help you obtain a balanced perspective of the pros and cons surrounding each treatment.

Patients with Gleason Scores 8-10, Stage T2c or a PSA greater than 20 or two intermediate factors, such as a PSA 10-20 and Gleason Score 7, are considered to have high risk disease. High risk simply means that there is a higher risk that disease is outside the prostate. Estimates of risk of disease beyond the prostate range from 23-88%. Most patients in this group have a risk of at least 50%, making them poor candidates for treatments that treat the prostate alone (i.e. surgery, seed implantation alone, EBRT to just the prostate). The graph results for surgery, for example, demonstrate that only 25-50% of patients will be successfully treated with surgery. There are no “good” high risk patients which can be definitively identified as being better candidates for local treatment alone. The graphs demonstrate that more aggressive treatments which combine treatments generally have better results.

Surgery for High Risk Disease
Surgery alone is generally a poor option in this group because the risk of the disease beyond the gland is calculated to be high. Estimates of risk of disease beyond the prostate range from 23-88% with an average of at least 50%. Surgery likely fails in high risk disease because there is often a significant amount of disease beyond the prostate which the surgery cannot remove. If you have doubt about this, the calculation of disease beyond the gland using the Partin Tables* can be very helpful as a confirmation, as can the 10-year results on the charts. We would rarely recommend surgery as a primary option for high risk disease.

External Beam Radiation (EBRT) for High Risk Disease
The routine use of external beam radiation has the ability to treat microscopic areas beyond the prostate than either surgery or seeds alone cannot treat. EBRT alone in this setting has resulted in only 35-65% of the patients being successfully controlled. External radiation does a good job of treating the prostate and the area immediately around it where cancer can spread. For high patients, external radiation likely fails in this setting due to an inability to give enough dose to control the disease in the prostate itself. The external dose that can be given to the prostate by external beam techniques is limited by the structures surrounding the prostate, primarily the rectum, bladder and hips. While techniques have been developed to minimize these areas receiving high doses, it is difficult to give doses beyond 75-81 Gy equivalent doses without a higher risk of rectal, bladder and hip injury.

External Beam Radiation (EBRT) and Hormonal Therapy for High Risk Disease
Hormonal therapy has been added to external beam radiation for high risk disease in an attempt to improve the effectiveness of this modality. The rationale is to kill as many cancer cells as possible prior to EBRT by temporarily blocking testosterone production. This approach thereby, theoretically, allows for fewer cells that the radiation needs to eradicate at the doses which can be safely delivered (75-81 Gy). In the short term as noted in the charts, this appears to be true. However the long term results, as observed in the charts for this approach, appear to be no better than EBRT alone. The course of hormonal therapy is debated but most centers restrict the hormonal therapy to 6-12 months with an occasional center giving it for up to three years.

External Beam, Seed Implantation Plus or Minus Hormonal Therapy for High Risk Disease
This triple modality approach for High Risk disease begins with the rationale that hormonal therapy may reduce the number of cells that need to be killed. EBRT can deliver an adequate dose to kill microscopic disease beyond the gland, and seed implantation can deliver a dose sufficient to control the disease within the gland. The small number of studies using this approach indicate that this rationale may be supported, with long-term cancer control rates of 85-92%. Note that this may be grade-dependent as the subset of high-risk patients with very high-grade (9-10) in less mature studies usually fare worse. The use of EBRT plus seeds appears to be quite variable from center to center. More studies will be needed to determine the best treatment. However, it appears from the charts that a combination of hormonal therapy (usually 6-9 months) with EBRT and seed implantation is superior to other regimens.

* Partin Tables – The Partin Tables use clinical features of prostate cancer – Gleason score, serum PSA, and clinical stage – to predict whether the tumor will be confined to the prostate. The tables are based on the accumulated experience of urologists performing radical prostatectomy at the James Buchanan Brady Urological Institute. For decades, urologists around the world have relied on the tables for counseling patients preoperatively and for surgical planning. Click for more information