==PROSTATE CARCINOMA BRACHYTHERAPY== 1 Petrovich Z, Baert L, Bagshaw MA, Brady LW, Elgamal A, Goethuys H, Heilman HP, Kirkels WJ, Lieskovsky G, Perez CA, Van Poppel H, Williams RD Adenocarcinoma of the prostate: innovations in management. Am J Clin Oncol; VOL 20, ISS 2, 1997, P111-9 (REF: 62) Adenocarcinoma of the prostate (CaP) in the Western world has become the most common noncutaneous human tumor. CaP is also the second most important cause of cancer deaths among the male population in the United States. Major progress was made in the past decade in better understanding this disease process, as well as in improved diagnostic accuracy. This improved diagnostic accuracy was due to wide application of prostate-specific antigen (PSA), use of transrectal ultrasound (TRUS), and greater awareness among clinicians of CaP. The use of PSA in clinical practice has resulted in a sharp increase in the number of patients diagnosed with capsule-confined tumors. The optimal treatment for capsule-confined CaP is in the process of being defined. Radical prostatectomy in the United States is currently the most commonly applied treatment for younger patients. Excellent treatment results with a 10-year actuarial survival > 80% are readily obtainable in properly selected patients. Nerve-sparing procedures helped reduce the high incidence of impotence that occurs in patients after radical retropubic prostatectomy. Radiotherapy remains the other curative treatment method in the management of CaP patients, with long-term survival rates similar to those reported in surgical series. Due to the problem of frequent preoperative tumor understaging, a routine use of postoperative irradiation to the prostatic fossa produces an excellent (> 95%) incidence of local tumor control. Management of patients with metastatic disease has undergone a considerable evolution with the development of modern hormonal management and treatment with strontium-89 to control intractable bone pain. Newer treatment methods such as hyperthermia are currently being investigated. Major efforts are directed toward the reduction of short- and long-term treatment toxicity associated with surgery, radiotherapy, and hormonal management, thus improving patient quality of life. 2 Ned Tijdschr Geneeskd 1996 Sep 14;140(37):1855-9 [Internal radiotherapy in prostatic carcinoma; disappointing long-term results of retropubic Iodine-125 implantation]. [Article in Dutch] Roeleveld TA, Horenblas S, Moonen LM, te Velde A, Meinhardt W, Bartelink H Nederlands Kanker Instituut/Antoni van Leeuwenhoek Ziekenhuis, Amsterdam. OBJECTIVE: To evaluate the results of retropubic implantation of 1-125 seeds in patients with carcinoma of the prostate. DESIGN: Retrospective study of records. SETTING: Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands. METHOD: A retrospective study of records provided follow-up data on 75 patients treated in the period 1981-1990 with implantation of 1-125 seeds by a retropubic approach, preceded by pelvic lymph node dissection. Criteria for the treatment were: To, T1 or T2 carcinoma of the prostate, prostatic volume < 40 ml, no contraindications to surgery. RESULTS: The median follow-up was 103 (60-157) months. Four patients died of complications (5%). Major postoperative complications occurred in 23% (17/75) of the cases. Residual carcinoma or distant metastasization was encountered in 43 of the 71 patients (61%). Sixteen patients died from the consequences of the prostatic carcinoma. The 5- and 10-year survival rates amounted to 74% and 42%, respectively, the cancer-specific 5- and 10-year survival rates to 85% and 67%, respectively. At the latest check-up, 18 patients were alive with tumour, 16 of them under hormonal treatment, while 21 patients were alive without indications of active prostatic carcinoma. CONCLUSION: Treatment of carcinoma of the prostate with retropubic implantation of 1-125 seeds resulted in a high incidence of local therapeutic failure and numerous postoperative complications. These results are poorer than those of total prostatectomy and external radiotherapy. 3 J Urol 1999 Apr;161(4):1212-5 Retrospective comparison of radical retropubic prostatectomy and 125iodine brachytherapy for localized prostate cancer. Ramos CG, Carvalhal GF, Smith DS, Mager DE, Catalona WJ Department of Surgery, Washington University School of Medicine, St. Louis, Missouri, USA. PURPOSE: Favorable results with 125iodine (I) brachytherapy have been reported in select patients with localized prostate cancer. We evaluate the results of radical prostatectomy in patients matched for similar pretreatment clinicopathological characteristics. MATERIALS AND METHODS: From May 1983 to April 1998, 1 surgeon (W. J. C.) performed radical retropubic prostatectomy in 1,952 men (mean age plus or minus standard deviation 63+/-7 years), of whom 1,364 had Gleason score 6 or less on preoperative needle biopsy, a preoperative serum prostate specific antigen (PSA) value available and clinical stage T1 or T2 disease. We categorized all patients by preoperative Gleason score, preoperative PSA and clinical stage. For each Gleason score-by-PSA stratum we randomly selected by computer the number of men necessary to achieve the same overall distribution of clinical characteristics as in a series of patients treated with brachytherapy. All men were followed with semiannual PSA measurements and annual digital rectal examinations. Serum PSA greater than 0.3 ng/ml was considered evidence of cancer recurrence. Simple univariate statistics were used to compare clinical characteristics between series, and 7-year recurrence-free survival was estimated using Kaplan-Meier product limit estimates. To avoid a possible chance extreme result from 1 random sample we estimated 7-year recurrence-free survival in 5 computer selected random samples of our population. RESULTS: Mean 7-year recurrence-free survival was 84% (95% confidence intervals 78 to 89) for the radical prostatectomy series compared to 79% (confidence intervals not provided) for the 125I brachytherapy series. CONCLUSIONS: Radical prostatectomy yielded a proportionately but not statistically significant higher 7-year probability of nonprogression than 125I brachytherapy in patients with favorable clinicopathological characteristics. Comparisons are confounded by residual differences in clinicopathological features of tumors between groups and different treatment end points to determine outcomes. Further prospective, randomized clinical trials are required for valid comparisons. 4 Hematol Oncol Clin North Am 1996 Jun;10(3):653-73 Does brachytherapy have a role in the treatment of prostate cancer? Grimm PD, Blasko JC, Ragde H, Sylvester J, Clarke D Tumor Institute Group of Seattle, Washington, USA. The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland either as permanent or temporary seeds. Permanent seed implantation is capable of delivering two times the radiobiologically equivalent dose of external beam irradiation to the prostate and tumor. In the past, the results of prostate brachytherapy were likely poor owing to the technical difficulty in accurately placing the radioactive seeds uniformly throughout the prostate. The use of low-dose-rate I-125 to treat high-grade cancers probably also contributed to the poorer results as compared with external beam irradiation. Over the last 10 years, however, technologic advances in transrectal ultrasonography, computer dosimetry, and template-based transperineal techniques have dramatically improved the accuracy and consistency of the brachytherapist to place radioactive sources directly into the prostate gland. Transperineal ultrasound or CT directed seed implantation has replaced the older retropubic method. Brachytherapists are now able to accurately map out the gland prior to the implant and carefully evaluate preoperatively seed placement. The availability of such radioactive sources as iodine-125, palladium-103, and iridium-192 has also given the brachytherapist isotopes that can be more carefully matched to the biology and stage of the tumor. More sensitive definitions of failure have prompted radiation oncologists and urologists to carefully evaluate the efficacy of external beam irradiation and surgery. Accurate comparison of the efficacy of brachytherapy to surgery and to external beam radiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Imbalances in stage, grade, initial PSA extraprostatic disease, and nodal status of patient groups make comparisons difficult. Most of the long-term data for permanent seed implantation are the result of work at a single institution. These results will need to be repeated at other institutions treating patients in a similar manner. Because techniques vary from institution to institution, permanent implant results will need to be carefully evaluated for technique as well as stratified for pretreatment variables. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after radiation. As more patients are diagnosed with very early and nonpalpable disease, future studies will need to stratify patients based on these pretreatment factors. Patients with early-stage disease but identified as high risk for extraprostatic disease will require more intensive regimens. The treatment outcomes based on biopsy results are inconclusive. A lack of consensus on the definition of a truly positive biopsy remains forthcoming. The value of a positive prostate biopsy as an outcome predictor for clinical failure is still unclear. The use of prostate nuclear cell antigen staining may help clarify the issue. Comparison of treatment outcome based on absolute PSA is also difficult. The Seattle series suggest that brachytherapy by permanent seed implantation is as efficacious as external beam irradiation for early-stage disease in patients with a low PSA (< 10 ng/mL). As the PSA value rises above 10 ng/mL, the probability of failure after external beam rises substantially. Results from the Seattle series suggest an advantage to seed implant alone or the judicious application of seed implant boost to external beam radiation for these patients with more advanced cancer. The most sensitive measurement of therapeutic outcome is progression-free survival. Few studies to date have evaluated progression-free survival. 5 Ned Tijdschr Geneeskd 1998 May 16;142(20):1146-51 [Iodine-125 implantation in localized prostate cancer; technique and results from 100 patients at the Academic Hospital, Utrecht]. [Article in Dutch] Battermann JJ, Zeijlemaker BY Afd. Radiotherapie, Academisch Ziekenhuis, Utrecht. OBJECTIVE: To evaluate the preliminary results of perineal implantation of I-125 seeds in patients with cancer of the prostate. DESIGN: Prospective descriptive cohort study. SETTING: Utrecht University Hospital, the Netherlands. METHODS: In the period from October 1989 to December 1996, a total of 149 patients with localized carcinoma of the prostate were treated with perineal implantation of I-125 seeds. One hundred of them could be evaluated. Results regarding progression and complications were collected prospectively. RESULTS: The median follow-up was 3 years (range 12-74 months). Progression of the disease was observed in 28 patients: local in eight, distant in four and both local and distant in one; 15 patients only showed a rise of prostate specific antigen level, without further symptoms. Fourteen patients were given supplementary treatment. No major complications were seen; four patients had persistent micturition problems and three, intestinal problems. CONCLUSION: Perineal I-125 implantation causes few complications and may constitute an alternative to external irradiation as well as to radical prostatectomy in the treatment of localized carcinoma of the prostate. 6 Int J Radiat Oncol Biol Phys 1997 Feb 1;37(3):559-63 Biochemical disease-free survival following 125I prostate implantation. Beyer DC, Priestley JB Jr Arizona Oncology Services, Phoenix 85013, USA. PURPOSE: To assess the 5-year clinical and biochemical results of ultrasound-guided permanent 125I brachytherapy in early adenocarcinoma of the prostate. Biochemical disease-free survival (BDFS) is reported, using PSA follow-up and is compared to the surgical and radiation therapy literature. METHODS AND MATERIALS: From December 1988 through December 1993, ultrasound-guided brachytherapy was preplanned with 125I and delivered 160 Gy as the sole treatment in 499 patients. All were clinically staged as T1 or T2 node-negative adenocarcinoma of the prostate. Within the first year, 10 patients were lost to follow-up and have been excluded from further study. The remaining 489 patients form the basis of this report. Clinical status and prostate specific antigen (PSA) values were systematically recorded before and after treatment. RESULTS: With a median follow-up of 35 months (3-70), the actuarial clinical local control is 83%. Both stage and grade are shown to predict for this endpoint. Actuarial biochemical disease-free survival (BDFS) is also correlated with stage, grade, and PSA at presentation. Biochemical disease-free survival at 5 years is 94% for T1, 70% for unilateral T2, and 34% for T2c tumors. Grade is also predictive, ranging from 85% in low-grade tumors to 30% in high-grade tumors. In a multivariate analysis, the pretreatment PSA is most highly correlated (p < 0.0001) with BDFS, local control, and clinical disease-free survival. Patients with a normal pretreatment PSA enjoyed 93% BDFS, while those presenting with PSA > 10 had a BDFS of 40%. Complications have been few, with severe urinary urgency or dysuria in 4% and both incontinence and proctitis seen in 1%. CONCLUSIONS: While biochemical disease-free survival reports in the literature are immature and have short follow-up, our data compares favorably with studies following radical prostatectomy or radiation therapy. Further follow-up of this cohort is required. The complication rate is low and patient acceptance excellent. Permanent implantation of 125I as the sole treatment for early prostate adenocarcinoma is a viable alternative for patients with early-stage and low- to moderate-grade cancers. The PSA provides significant prognostic information and aids in case selection. Better management options are needed for high grade and bilateral tumors. 7 Hematol Oncol Clin North Am 1996 Jun;10(3):653-73 Does brachytherapy have a role in the treatment of prostate cancer? Grimm PD, Blasko JC, Ragde H, Sylvester J, Clarke D Tumor Institute Group of Seattle, Washington, USA. The goal of radiation therapy is to deliver a high dose to the tumor while preserving normal surrounding tissue. For early-stage prostate cancer, the ultimate conformal irradiation is to place radioactive sources directly into the gland either as permanent or temporary seeds. Permanent seed implantation is capable of delivering two times the radiobiologically equivalent dose of external beam irradiation to the prostate and tumor. In the past, the results of prostate brachytherapy were likely poor owing to the technical difficulty in accurately placing the radioactive seeds uniformly throughout the prostate. The use of low-dose-rate I-125 to treat high-grade cancers probably also contributed to the poorer results as compared with external beam irradiation. Over the last 10 years, however, technologic advances in transrectal ultrasonography, computer dosimetry, and template-based transperineal techniques have dramatically improved the accuracy and consistency of the brachytherapist to place radioactive sources directly into the prostate gland. Transperineal ultrasound or CT directed seed implantation has replaced the older retropubic method. Brachytherapists are now able to accurately map out the gland prior to the implant and carefully evaluate preoperatively seed placement. The availability of such radioactive sources as iodine-125, palladium-103, and iridium-192 has also given the brachytherapist isotopes that can be more carefully matched to the biology and stage of the tumor. More sensitive definitions of failure have prompted radiation oncologists and urologists to carefully evaluate the efficacy of external beam irradiation and surgery. Accurate comparison of the efficacy of brachytherapy to surgery and to external beam radiation requires a randomized study. Comparisons of retrospective studies are fraught with the problems of the heterogeneous nature of early-stage prostate cancer. Imbalances in stage, grade, initial PSA extraprostatic disease, and nodal status of patient groups make comparisons difficult. Most of the long-term data for permanent seed implantation are the result of work at a single institution. These results will need to be repeated at other institutions treating patients in a similar manner. Because techniques vary from institution to institution, permanent implant results will need to be carefully evaluated for technique as well as stratified for pretreatment variables. Pretreatment PSA and grade appear to be more sensitive variables than stage in predicting failure after radiation. As more patients are diagnosed with very early and nonpalpable disease, future studies will need to stratify patients based on these pretreatment factors. Patients with early-stage disease but identified as high risk for extraprostatic disease will require more intensive regimens. The treatment outcomes based on biopsy results are inconclusive. A lack of consensus on the definition of a truly positive biopsy remains forthcoming. The value of a positive prostate biopsy as an outcome predictor for clinical failure is still unclear. The use of prostate nuclear cell antigen staining may help clarify the issue. Comparison of treatment outcome based on absolute PSA is also difficult. The Seattle series suggest that brachytherapy by permanent seed implantation is as efficacious as external beam irradiation for early-stage disease in patients with a low PSA (< 10 ng/mL). As the PSA value rises above 10 ng/mL, the probability of failure after external beam rises substantially. Results from the Seattle series suggest an advantage to seed implant alone or the judicious application of seed implant boost to external beam radiation for these patients with more advanced cancer. The most sensitive measurement of therapeutic outcome is progression-free survival. Few studies to date have evaluated progression-free survival. 8 Zachow SE, Hargis R Department of Radiation Oncology, Methodist Medical Center, Jackson, MS, USA. The definitive treatment of prostate cancer remains controversial although certainly radical prostatectomy is the standard all other treatments must be compared against. However, there potentially can be a multitude of complications as well as extensive hospitalization and costs involved in surgical removal of the prostate gland. The use of radiation therapy in a variety of forms has been proven to be a reasonable alternative. This paper will discuss the use of radioactive seed implants that can be performed transperineally using transrectal ultrasound as a guide. This requires only an overnight stay and appears to provide an excellent chance of a cure with minimal potential morbidity.