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Abstract & Commentary
Synopsis: The use of implantable iodine-125 or palladium-103 seeds for prostate cancer has increased as biochemical cure rates have been shown to be comparable to those after surgery or external beam radiotherapy. Patients are becoming increasingly aware of the toxicity profiles of the various therapeutic modalities, and may use them as the determining factors in treatment selection. This study, from a Memorial-Sloan Kettering affiliate center, studied an important quality-of-life issue, potency outcomes, in the largest prospective study to date. They showed that the highest 5-year actuarial rate of potency preservation, 76%, occurred in patients treated with seeds alone, while the lowest rate, 29%, was seen in patients subjected to trimodality therapy with a combination of seeds, hormone ablative therapy, and external beam radiotherapy.
Source: Potters L, et al. Int J Radiat Oncol Biol Phys. 2001;50:1235-1242.
Prior to seed therapy for localized prostate cancer, a sexual history was obtained from 1166 consecutive patients seen at a MSKCC affiliate center between September 1992 and September 1999. All patients had T1b-T2b disease. Based on inquiries regarding potency status, it was determined that 41% of patients were potent (n = 482). Potency was defined as the ability to achieve an erection sufficient for intercourse without the use of any device or medication. More than half of men > 70 years were impotent, and almost one-third of men 50-55 years were impotent. The potent men were selected to study the impact of therapy on their potency status. The median PSA for the study group was 8, and median patient age was 68 years (range, 49-81 years).
Patients were treated with either iodine-125 or palladium-103 seeds alone, seeds and external beam radiotherapy, or trimodality therapy with the addition of androgen ablation. Brachytherapy and external beam therapy techniques and doses were standard. Patients received seeds alone if their PSA was < 10 and their Gleason score was < 6. All other patients received 41.4-45 Gy 4-field external beam therapy prior to seed implantation per the American Brachytherapy Society guidelines. The 126 patients whose prostates exceeded 60cc in volume (26%) received a median of 4.2 months (range, 1.2-9.5 months) of neoadjuvant hormonal therapy in order to shrink their glands to make implantation feasible. Follow-up was performed in the clinic or by contacting the patient. Median follow-up was 34 months (range, 6-92 months). Potency status for analysis purposes was based on status at the time of the last follow-up visit.
The 5-year actuarial potency status for the entire group was 53%. The patients who did the best were those treated with seeds alone (n = 246, 51%). Their rate of potency preservation was 76%. This was significantly better than for patients treated with seeds preceded by hormone ablative therapy, where 5-year actuarial potency was 52% (P = .0001). It was also better than potency preservation in patients who received a combination of external beam radiotherapy and seeds without hormones (56%), but not statistically significantly better (P = .08). There was no statistically significant difference in potency status between the latter group and patients treated with all 3 modalities (29%, P = .48), although patients given maximal therapy did the worst. A comparison of potency status for patients receiving seeds and hormones did not show a significant difference vs. patients getting seeds, external beam RT, and hormones (P = .13).
Cox proportional hazards analysis of the results showed that age (P = .0001) and use of hormones (P = .04) were significantly related to loss of potency following implantation, while use of external beam radiotherapy was not (P = .11). Among patients who became impotent following therapy, 62% (52/84) responded to silfenadil (Viagra®), including 83% (30/36) of patients who did not receive hormone therapy, and 46% (22/48) of those who did.
Potters et al concluded that hormonal therapy compromises what would otherwise be attractive potency rates in those patients treated with seed implantation. They cited their own retrospective work showing a lack of improvement in biochemical cure rates by the addition of hormone therapy and/or external beam therapy as a rationale to avoid stacking those therapies.1 They further cited the lack of randomized data supporting combination therapy as a reason to avoid it.
Comment by Edward J. Kaplan, MD
This study confirmed that more therapy means more side effects. The use of hormones had a tremendous impact on patients’ potency status in this report. While external beam therapy was added to the treatment plan for patients with high-risk features (ie, PSA > 10 or Gleason score > 6) the goal of using hormones was to shrink prostates that were considered to be too large to implant. Therefore, as long as size is a barrier to implanting prostates, it becomes difficult to do without hormones. The group that was least affected by the addition of hormones was men < 60 years, who suffered a 24% drop in potency when hormones were added to seeds. This drop increased to 37% if external beam therapy was added. The group that was hurt the most in terms of potency status was men > 70 years. Their potency rate dropped 50% when hormones were added, and it dropped 80% compared to seeds alone if trimodality therapy was used.
Ultimately, the impact of potency enhancers on impotence should not be ignored. Overall, if one considers the 52/84 impotent patients whose potency was restored via silfenadil, 75% of the patients in Potters’s study were potent post-treatment. A closer examination shows that nonhormone users did significantly better than hormone users in regaining lost potency (83% vs 46%; P = .04).
Although the mechanism for induction of impotence by radiation therapy is not clear, it has been shown that impotence can be reversed with medication. This becomes much more difficult to achieve if hormones are used, and is difficult to justify if no survival benefit associated with hormone use can be demonstrated. Until randomized study data have been reported, men who are contemplating seed implantation must be made aware of the potential long-term effect of hormone therapy on their quality of life.
1. Potters L, et al. J Clin Oncol. 2000;18:1187-1192.