Reviewers: John Han-Chih Chang, MD
Source: Journal of the American Medical Association (JAMA), September 16, 1998; Volume 280, Number 11
Radical surgery (prostatectomy), external beam radiation therapy and interstitial brachytherapy (radiation therapy with radioactive seed implantation) modalities form the triadof choice for prostate cancer patients who seek a curative intervention for their malignancy. There are no documented randomized prospective studies that address the questionas to efficacy of one modality in relation to the other. This retrospective review is the collaboration of two ivy league institutions (the Joint Center for Radiation Oncology- Harvard Medical School and the Hospital of the University of Pennsylvania). It details their experience between the three treatment options.
One thousand eight hundred and seventy-two charts were reviewed. These patients were men with clinically localized prostate cancer seen or diagnosed between 10/97and1/98. Radical prostatectomy was performed in 888 men, while interstitial brachytherapy was utilized in 218 patients. Both these populations came from the Hospital of theUniversity of Pennsylvania (HUP). Conformal external beam radiation therapy was delivered to 766 patients from the Joint Center for Radiation Oncology (JCRT).
The clinical staging was from digital rectal examination findings only and in accord with the 1992 AJCC staging system. All pathological specimens were reviewed by onecentral pathologist at each of the respective institutions.
Radical surgery consisted of a radical retropubic prostatectomy and bilateral pelvic lymph node sampling. External beam radiation therapy was delivered with a megavoltagelinear accelerator with at least 10 MeV photons in a conformal 4-field technique. For early stage (T1c, T2a; PSA 10 or less and Gleason score 2 ? 6) disease, the prostatewith 1.5 cm margin was treated with 66 ? 70 Gy. For all others with clinically localized prostate malignancy, the prostate and seminal vesicles were initially treated to 45 ?50 Gy, followed by a 18 ? 22 Gy treatment to prostate alone. The implant patients were treated with palladium 103 seeds utilizing transrectal ultrasound/perineal templateguidence for placement. Minimum peripheral prostate gland dose was 115 Gy. Seventy percent of implant patients received neoadjuvant androgen deprivation therapy for amedian of 3 months prior to receiving the implant.
Median follow-up was 38, 38 and 41 months for the prostatectomy, external beam and interstitial radiation therapy patients, respectively. None were lost to follow up andall were alive at the time of analysis.
Patients were stratified in the analysis by prognostic factors: 1) low risk = T1c and T2a, PSA less than or equal to 10 and Gleason score 6 or less. 2) high risk = T2c, PSAgreater than 20 and Gleason score 8 or greater. 3) intermediate risk is anyone else. Patients also were stratified by Gleason score 2 ? 4, 5 ? 6, 7, 8 ? 10. Biochemical orPSA failure was defined by the American Society of Therapeutic Radiology and Oncology 1996 consensus statement for all study patients (being 3 consecutive rises/ 3months apart in PSA after the lowest value was attained).
No significant differences were seen in the patient characteristics between the three treatment modalities among low to intermediate risk patients. Among the high riskpatients, there was a higher proportion of patients that had lower (less than or equal to 10) PSA?s in the implant patients treated with neoadjuvant androgen ablation. Thismay have served as a bias had the outcome of the high risk patients treated with the brachytherapy been relatively better than the other treatments ? this was not the case aswe see later.
The relative risk of PSA failure was the same across all three treatment modalities for low risk or a Gleason score 2 ? 6 patients. In the high risk or a Gleason score 8 ? 10population, patients treated with radical prostatectomy and external beam radiation therapy had a decreased risk of biochemical failure than any of the implant patients. Thosethat had intermediate risk or a Gleason score of 7 disease and received implants without neoadjuvant androgen ablation had a significant risk of PSA failure when contrastedto radical prostatectomy or external beam radiation therapy. These patient?s outcome improved when neoadjuvant androgen ablation was utilized prior to the implant.Figures 1 through 7 demonstrate these issues graphically.
This paper details some very preliminary results on the three most utilized definitive treatment modalities for localized prostate cancer. The results are very early withmedian follow up of only just over 3 years. For prostate cancer, that may not be long enough to determine efficacy. Overall, it appears that for early stage of disease, allthree modalities are equally effective. As more prognostic factors arise, the LESS the likelihood that prostate implantation without neoadjuvant androgen ablation will beeffective based on the data shown. With the intermediate risk and Gleason score 7 patients, the addition of neoadjuvant androgen ablation appears to equalize the results perfigures 2 and 6. Some would argue that all this represents is the phenomenon of hormone-induced delay in PSA failure and NOT a biochemical disease free benefit.
A confounding factor is that the pathology was not centrally reviewed between the two institutions. The discordance between one pathologist and the other for Gleason scorehas been documented to be as high as 50% in the literature. This may make the difference between a 6 versus a 7 versus an 8, which may sway the recommendation ofphysicians and the decision of the patients.
Another unanswered question is the efficacy of palladium 103 versus iodine 125 seeds. Iodine 125 seeds have been the standard initially, but the palladium 103 seeds havecome onto the scene with claims that a higher radiation dose rate and shorter half-life were more efficacious. The iodine 125 supporters argue that a higher dose is given withthe iodine seeds over a longer period of time (longer half-life) yields a lower toxicity and higher efficacy rate. Could this be the reason why implants were not as effective inthe poorer prognosis patients.
Overall, treatment for clinically localized prostate cancer remains controversial. This article details very preliminary results of the retrospective review of two institutions?experience with this malignancy. It is truly difficult to make any definitive decisions based on this review, because of the short follow up. The number at risk in theimplant-treated population are few and far between (range 0 ? 8) in the intermediate risk, high risk and Gleason 7 and above patients, who were more than 2 years out fromdiagnosis. One cannot make significant comparisons with those numbers when the surgery and external beam patient numbers are 3 ? 4 fold more. Even with all thoseconsiderations, the trend appears to favor either surgery or external beam radiation therapy for high Gleason scores and risk groups. There appears to be NO difference inPSA outcome for patients with low Gleason scores and risk group. The intermediate risk and Gleason score 7 patients are in a controversial area. Implants may not beadequate treatment for them, but as with anything in medicine ? physicians and patients must individualize. The patient is not a percentage, he either fails 100% or not atall.