Urinary morbidity and incontinence following transurethral resection of the prostate after brachytherapy.

PURPOSE: We analyzed the risk of urinary morbidity and incontinence in patients undergoing transurethral resection of the prostate (TURP) following prostate brachytherapy. MATERIALS AND METHODS: A total of 2,050 patients underwent transperineal radioactive seed implantation of the prostate with or without external beam radiation therapy for the diagnosis of prostate cancer between June 1990 and February 2004. Of the 2,050 patients 38 (2%) underwent minimal (channel) TURP due to urinary symptoms or retention. Urinary morbidity was recorded prior to implantation and at followup intervals using the International Prostate Symptom Score and quality of life assessment scores. All patients underwent post-implantation computerized tomography based dosimetry at 1 month. The dose to 90% of prostate volume, prostate volume covered by 15% of the prescription dose and dose to 30% or 5 cm of urethral volume were recorded. Of the 38 patients 11 (29%) underwent Pd implantation alone and 12 (32%) received a partial (67%) Pd implant with external beam radiation therapy to a median dose of 45 Gy (range 41.4 to 59.4), while 15 (39%) underwent I implantation alone. Median followup after implantation was 38 months (range 2 to 97). RESULTS: Seven of the 38 patients (18%) undergoing TURP had urinary incontinence. Median time to TURP was 11 months (range 1 to 73). 25% Of patients who received an implant and external beam radiotherapy had urinary incontinence following TURP compared with 15% who underwent implantation alone (p = 0.26). There was no significant correlation between incontinence risk based on the dose to 90% of prostate volume (p = 0.32), the dose to 30% or 5 cm of urethral volume (p = 0.30) or prostate volume covered by 15% of the prescription dose (p = 0.36). Two of 24 patients (8%) who had underwent 2 years or less after implantation had urinary incontinence compared with 5 of 14 (36%) who underwent TURP greater than 2 years following implantation (p = 0.04). CONCLUSIONS: Urinary incontinence developed in 18% of patients who underwent TURP following prostate brachytherapy. No significant correlations between radiation dose, preimplant prostate volume or hormonal therapy were identified with regard to this risk. Patients in late retention or with obstructive symptoms (greater than 2 years) following implantation who require TURP are at greater risk for incontinence.

Serum interleukin-8 is elevated in men with prostate cancer and bone metastases.

Aalinkeel et al. (1) have recently reported that gene expression of angiogenic factors correlates with metastatic potential of prostate cancer cells. The rationale for the study of Aalinkeel et al. is that a variety of growth factors, among them interleukin-8 (il-8), can induce angiogenesis (2). Further, parathyroid hormone related peptide (PTHrP) acts to induce il-8 production in prostate cancer cells via an intracrine pathway independent of its classical nuclear localization sequence. This novel pathway could mediate the effects of PTHrP on the progression of prostate cancer (3). We measured il-8 in the serum of 39 men with biopsy-proven prostate cancer. Their average age was 69 +/- 9 (mean +/- SD). Serum il-8 was measured with an automated chemiluminometric high sensitivity il-8 protein assay (Immulite, Diagnostic Products Corporation, Los Angeles, CA). We noted a significant elevation of il-8 in men with bone metastases, diagnosed by Tc-99 MDP bone scan, when compared to men with localized disease (Figure 1). Aalinkeel et al. found that il-8 was significantly higher in the more metastatic PC-3 and DU-145 prostate cancer cell lines, when compared to the poorly metastatic LnCAP cells. The results of our study of il-8 in men with prostate cancer support the findings of Aalinkeel et al. Therefore, new anti-angiogenic therapies targeting specific genes controlling prostate tumor metastasis may be of benefit in treating prostate cancer.

Putative protein markers in the sera of men with prostatic neoplasms.

OBJECTIVE: To describe the preliminary identification of serum proteins that may be diagnostic markers in prostate cancer. PATIENTS AND METHODS: The study included 11 men referred for treatment of localized prostate cancer, 12 with benign prostatic hyperplasia (BPH) and 12 disease-free controls. For serum protein analysis, the protein-chip array surface-enhanced laser desorption/ionization (SELDI) technique was used (Ciphergen Biosystems, Fremont, CA). SELDI combines protein-chip technology with time-of-flight mass spectrometry, and offers the advantages of speed, simplicity and sensitivity. RESULTS: Three protein peaks were identified in the serum of men with prostate cancer and BPH, but not in controls, with relative molecular masses of 15.2, 15.9 and 17.5 kDa. These three proteins were significantly associated with BPH and prostate cancer when compared with controls (P = 0.001, 0.004, and 0.011, respectively, Kruskal-Wallis test). Interestingly, the 17.5 kDa protein was more abundant in five men with stage T1 prostate cancer than in eight with stage T2 (P = 0.016, two tailed Mann-Whitney U-test corrected for ties). CONCLUSIONS: These proteins, particularly the 15.9 kDa one, may be used for the diagnosis or monitoring of prostate cancer and differentiation from BPH, and have the potential for antibody-based chip SELDI-TOF technology. Identified proteins may be targets for immunotherapy.

Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer.

In the present study, we assessed the relationship of serum insulin levels and three surrogate markers of recurrence, T stage, PSA, and Gleason score, in men with localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients were asymptomatic and had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum insulin levels were determined by chemoluminescent assay with a standard, commercially available instrument. Patients were divided into three previously defined risk groups: Low risk: PSA < or =10, stage < or =T2a, or Gleason grade < or =6. Medium risk: 10 7, tumour in seminal vesicle biopsy, PSA >15 or stage T2c or T3. One hundred and sixty-three men with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P=0.003, one way anova). Tukey's multiple range test showed that the insulin levels of high risk patients were significantly higher than the insulin levels of medium and low risk patients (P=0.05) but the insulin levels of medium and low risk patients were not significantly different from one another. Multivariate linear regression, with insulin as the dependent variable, Gleason score, PSA, and T stage (T1, T2, T3) as the independent variables, was significant overall (P<0.001, r(2)=0.120). Increased T stage was independently correlated with increased serum insulin levels (P<0.001). Gleason score was negatively, insignificantly correlated with serum insulin level (P=0.059). The positive correlation of PSA and insulin level was not significant (P=0.097). To assure normal distribution of insulin and PSA values, the regression was repeated with log (insulin) as the dependent variable, log (PSA), T stage (T1, T2, T3), and Gleason score as independent variables. The regression was significant overall (P=0.002, r(2) =0.095). Increased T stage was independently correlated with increased log (insulin level) (P=0.026). Gleason score was negatively, insignificantly correlated with log (insulin) level (P=0.728). The positive correlation of log (PSA) and log (insulin) levels was significant (P=0.010). The relationship between increased insulin level and advanced tumour stage in prostate cancer we describe here is biologically quite plausible, since insulin is a growth factor. Further studies may document whether serum insulin levels might be a useful biomarker of prostate cancer stage.

Complications following permanent prostate brachytherapy.

OBJECTIVES: The acute and chronic complications of permanent prostate brachytherapy are discussed. MATERIALS AND METHODS: Review of literature for the complications associated with iodine-125 (125I) and palladium-103 (103Pd) prostate brachytherapy. Acute complications included urinary retention, changes in the International Prostate Symptom Score (IPSS) and need for TURP. Chronic morbidity included permanent urinary symptoms, incontinence, radiation proctitis and erectile dysfunction. RESULTS: Urinary retention occurred in 1.5-22% of the patients postimplant. Acute urinary symptoms increased by over 100% 1 month after the procedure. By 12 months, the symptoms were either back to baseline or slightly elevated in over 90% of the patients. Significant obstructive symptoms or persistent urinary retention necessitating TURP occurred in 0-8.7%. Urinary incontinence was found in 0-19% treated by implant without associated TURP, in 0-85% for those who had a TURP prior to the implant and in 0-17% for those who had the TURP subsequent to the implant. Potency rates ranged from 34% to 86% 1-6 years postimplant. Radiation proctitis was found in 0.5-21.4%, with significant injury (fistula) occurring in 1-2.4%. CONCLUSIONS: The data from this report suggests that permanent prostate brachytherapy can be accomplished with minimal short- and long-term morbidity. Attention to detail as well as an appreciation to the causative factors for the morbidity will help reduce treatment-related side effects.

Intraoperative planning and evaluation of permanent prostate brachytherapy: report of the American Brachytherapy Society.

PURPOSE: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP). METHODS AND MATERIALS: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique. RESULTS: The ABS proposes the following terminology in regard to prostate planning process: *Preplanning--Creation of a plan a few days or weeks before the implant procedure. *Intraoperative planning--Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. * Intraoperative preplanning--Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. *Interactive planning--Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. *Dynamic dose calculation--Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints. CONCLUSION: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.

Defining the risk of developing grade 2 proctitis following 125I prostate brachytherapy using a rectal dose-volume histogram analysis.

OBJECTIVE: To determine the rectal tolerance for developing Grade 2 radiation proctitis after 125I prostate implantation based on the rectal dose-volume histogram. METHODS AND MATERIALS: Two hundred twelve patients with T1-T2 prostate cancer underwent 125I implantation without external beam irradiation. One month after the procedure, all patients underwent CT-based postimplant dosimetry (3-mm abutting slices). The rectal volumes, defined by an inner and outer wall, were determined from 9 mm above the seminal vesicles to 9 mm below the prostate apex. All doses were calculated by TG43 formalism. The prostate prescription dose was 160 Gy. A dose response analysis was undertaken for volumes of rectal tissue receiving a given dose. Dose levels examined were 80 Gy, 100 Gy, 120 Gy, 140 Gy, 160 Gy, 180 Gy, 200 Gy, 220 Gy, and 240 Gy. Grade 2 proctitis was defined as rectal bleeding occurring at least once a week for a minimum period of one month. The risk of proctitis was calculated using actuarial methods. For each dose level, a critical volume cutpoint was chosen to define a low and high volume group of patients. The cutpoint was determined based on two goals: minimizing thep value and finding a < or =5% risk of proctitis in the low volume group. Patients were followed from 12 to 61 months (median: 28 months) after implantation. RESULTS: Twenty-two patients developed Grade 2 proctitis: 14% within the first year, 72% between the first and second year, and 14% during the third year after the implant date. After the third year postimplantation, no cases of proctitis were reported. Proctitis was found to be significantly volume dependent for a given dose. The prescription dose (160 Gy) delivered to < or =1.3 cc of rectal tissue resulted in a 5% rate of proctitis at 5 years vs. 18% for volumes >1.3 cc (p = 0.001). Similar results were found for all doses examined. As the rectal volume receiving the prescription dose (160 Gy) increased, so did the proctitis rate: 0% for < or =0.8 cc, 7% for >0.8-1.3 cc, 8% for >1.3-1.8 cc, 24% for >1.8-2.3 cc, and 25.5% for >2.3cc (p = 0.002). CONCLUSIONS: Rectal dose-volume histogram analysis is a practical and predictive method of assessing the risk of developing Grade 2 proctitis after 125I prostate implantation. Delivered dose should be kept below defined rectal volume thresholds to minimize this risk. This information can allow one to decrease rectal morbidity by modifying prostate implant technique.

Penile erectile function after permanent radioactive seed implantation for treatment of prostate cancer.

PURPOSE: We assess erectile function after prostate brachytherapy and analyze those factors affecting potency preservation. MATERIALS AND METHODS: A total of 416 patients treated from October 1990 to September 1998 with permanent radioactive seed implantation for T1 to T2 prostate cancer had erectile function assessed before and after treatment. Erectile function was assessed using the scoring system of 0-complete inability to have erections, 1-able to have erections but insufficient for intercourse, 2-can have erections sufficient for intercourse but considered suboptimal and 3-has normal erectile function. Implant dose was defined as the D90, which was the dose delivered to 90% of the gland on a dose volume histogram from the 1-month computerized tomography based dosimetric analysis. RESULTS: Pretreatment erectile function assessment revealed scores of 0 in 57 (14%), 1 in 46 (11%), 2 in 77 (18%) and 3 in 236 (57%) patients. In 313 patients who were potent with a score 2 or greater before therapy the actuarial freedom from any decrease in erectile function score was 64% and 30% at 3 and 6 years, respectively. The actuarial preservation of potency, with a score 2 or greater, was 79% and 59% at 3 and 6 years, respectively. The 2 factors found to have a significant negative effect on potency in univariate and multivariate analyses were high implant dose (D90 greater than 160 Gy. for I-125 and D90 greater than 100 Gy. for Pd-103) and a pretreatment erectile function score of 2 versus 3. CONCLUSIONS: The rate of potency preservation after brachytherapy is high, although a decrease occurs from 3 to 6 years. Pretreatment erectile dysfunction as well as higher implant dose are associated with greater impotency.

Association between serum triiodothyronine (t3) level and risk of disease recurrence in men with localized prostate cancer.

We assessed the relationship of serum triiodothyronine (t3) level and risk of disease recurrence in men treated for localized prostate cancer. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising prostate specific antigen (PSA) or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Serum (t3) level was determined by chemoluminescent assay with a standard, commercially available instrument (Immulite Diagnostic Products Corporation, Los Angeles, California). Sixty-eight men with prostate cancer were studied. In our treatment protocol, patients are divided into three risk groups: low risk: serum PSA7, tumor in seminal vesicle biopsy, serum PSA >15 or stage T2c or T3. These patients are treated with 3 months combined hormonal therapy, an implant, and after 2 months break 6000 rad external beam radiotherapy. There was a significant increase in serum t3 with risk category (P=0.011). Tukey's multiple range B-test showed a significant difference between the t3 levels of the high risk patients, when compared to the t3 levels of the moderate (P=0.013) and low risk patients (P=0.041). The range test showed no significant difference between the t3 levels of the moderate and low risk patients (P=0.897). Because t3 levels may be affected by age, we performed multivariate linear regression, with t3 as the dependent variable. There was a statistically significant (P=0.035) association of t3 level with risk group, but there was no significant association of t3 with age (P=0.803). Multivariate linear regression, with t3 as dependent variable, PSA, Gleason score, and stage as independent variables showed a significant overall association of the three independent variables with t3 (P=0.042), though individually the relationships were not significant. None of the men had a t3 level that was above the normal range for our laboratory (137 ng/dl). Urologists are actively seeking additional biomarkers of prostate cancer aggressiveness. Many prostate cancers are quite indolent and may never cause a problem, but it is impossible to identify such tumors with certainty. Further studies of serum t3 level as a biomarker in prostate cancer might therefore be worthwhile. With more and better biomarkers, many older men might be spared the rigors of radiation therapy and/or surgery and the complications. Also, new prostate cancer therapies might be directed toward inhibiting the mitogenic effects of t3.Prostate Cancer and Prostatic Diseases (2001) 4, 232-234.

Body mass, age, and the APC I1307K allele in Ashkenazi Jewish prostate cancer patients.

The I1307K mutation of the adenopolyposis coli gene (APC), located on chromosome 5q21-q22, is associated with an increased risk of cancer in Ashkenazi Jews. In the present study, we analyzed age and body mass of Ashkenazi Jewish prostate cancer patients, with and without the APC I1307K mutation. Participants in our study were found through urology and radiation oncology clinics, and all eligible patients were asked to take part. A familial history was obtained by interview or self-report questionnaire. Histological confirmation of diagnosis was obtained for all subjects. The I1307K allele of the APC gene was detected by amplification of lymphocyte DNA from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. We studied 135 Ashkenazi Jewish men with prostate cancer. The youngest was 49, the oldest 80, average age 68 +/- 6.88 (mean +/- SD). The older patients carrying the wild type APC allele tended to have a lower body mass than the younger ones (r = -.27, P =.002). Of 71 patients under 70 years old, 65 carried the wild type APC allele, and had a body mass index of 28. 7 +/- 4.23 kg/m(2). The six men under age 70 carrying the I1307K APC allele had a body mass index of 26.87 +/- 1.44 kg/m(2). The difference in body mass index of the two groups is significant (P =. 032, t test for unequal variance). Increased body mass is a prostate cancer risk factor, and hereditary prostate cancer is associated with younger patients. Therefore, our finding, that patients under age 70 carrying the I1307K allele are significantly thinner than those carrying the wild type allele, suggests that the APC I1307K allele is also a prostate cancer risk factor. Our results are in accord with other studies indicating that APC mutations increase the risk of prostate cancer.

Effects of neoadjuvant hormonal therapy on prostate biopsy results after (125)I and (103)Pd seed implantation.

BACKGROUND: Androgen ablation may improve the efficacy of radiation therapy. PATIENTS AND METHODS: A total of 296 patients who had either (125)I (206; 70%) or (103)Pd (90; 30%) transperineal prostate brachytherapy (no external-beam radiation) had routine transrectal ultrasound-guided needle biopsy (minimum six cores) 2 years after treatment without regard to disease status. Neoadjuvant hormonal therapy (NHT: leuprolide acetate and flutamide) was used in 115 patients (39%) for 3 months prior to and 3 months after the implant. RESULTS: Of the 296 patients, 30 (10%) had positive prostate biopsies. Biopsies were positive in 4 of 115 (3.5%) v 26 of 181 (14%) of those who received or had not received NHT, respectively (P = 0.002). When patients were separated into low risk (PSA < or = 10 ng/mL, stage < or = T(2a), and Gleason score < or = 6) and high risk (all others), it was seen that low-risk patients did not benefit from NHT (3.8 v 7.7% positive biopsy rate; P = 0.5) whereas high-risk patients did (3.4% v 21.1%; P = 0.003). CONCLUSION: Prostate brachytherapy yields high negative biopsy rates (90%) 2 years after treatment. Neoadjuvant hormonal therapy can improve the local control rates (as determined by biopsy) in patients undergoing (125)I or (103)Pd seed implantation. These results are most significant for patients who present with PSA >10 ng/mL, stage > or = T(2b) diseases, or Gleason score > or = 7 (high-risk status).

Postimplant dosimetry for (125)I prostate implants: definitions and factors affecting outcome.

OBJECTIVE: An analysis of CT-based dosimetry was performed to assess the efficacy of the real time method of prostate implantation, explore the relationship of various dose descriptions and determine implant factors affecting outcome. METHODS AND MATERIALS: Between 7/95 and 8/99, 297 patients underwent (125)I implants for T1-T2 prostate cancer and had CT-based dosimetry performed (TG43 formalism). Dosimetry was performed 1 month postimplant. Using a dose-volume histogram, doses delivered to 100%, 95%, 90%, and 80% of the prostate (D100, D95, D90, D80, respectively) as well as percentages of the gland receiving 240 Gy, 160 Gy, 140 Gy (V240, V160, V140, respectively) were reported. Correlations between the various dose parameters and D90 were generated. The effect of the number of seeds implanted, seeds/volume, prostate volume, experience as assessed by time (8/01/99-date of implant), ultrasound probe (mechanical sector vs. dual phased electronic), and the ratio of the CT dosimetry prostate volume/ultrasound implant volume (CT/US vol) were analyzed. RESULTS: The median D100, D95, D90, and D80 values were 10,200 cGy, 15,655 cGy, 17,578 cGy, and 19,873 cGy, respectively. The median V240, V160, and V140 were 56%, 94%, and 98%, respectively. Correlations of dose descriptions found a close relationship of D95, D80, V240, V160, and V140 with D90 with r values of 0.928, 0.973, 0.911, 0.816, and 0.733, respectively. D100 correlated poorly with D90 (r = 0.099). Using a stepwise regression analysis, CT/US vol ratio, prostate volume, and seed number were the only significant factors affecting D90 with CT/US vol ratio having the greatest effect. The dual-phased electronic probe was associated with fewer D90 values of less than 140 Gy (2%) compared to the mechanical sector probe (14%) (p = 0.02). CONCLUSION: CT-based dosimetry results reveal the real-time implant technique to be an effective method of prostate implantation. Factors associated with more precise implantation, such as decreased postimplant edema, new technology, and increased number of seeds will lead to higher D90 values.

The effect of disease and treatment-related factors on biopsy results after prostate brachytherapy: implications for treatment optimization.

BACKGROUND: Posttreatment prostate biopsy is a method of assessing local control after irradiation for prostate carcinoma. An analysis of the effect of disease- and treatment-related factors on biopsy results after prostate brachytherapy was performed to aid in patient selection and treatment optimization. METHODS: Two hundred sixty-eight patients underwent posttreatment prostate biopsy (6-8 cores) 2 years after brachytherapy alone without external beam irradiation. Follow-up ranged from 24 to 111 months (median, 43 months). Implants were performed using a real-time ultrasound guided technique with the isotopes (125)I in 186 and (103)Pd in 82 patients. Ninety-eight patients underwent hormonal therapy (HT) 3 months before and 2-3 months after implant. Implant dose was defined as the D90 (dose delivered to 90% of the gland from the dose volume histogram generated using 1-month computed tomography-based dosimetry). RESULTS: Overall, 89% of patients (238 of 268) had negative biopsies. A positive biopsy was a predictor of biochemical failure. Patients with a positive biopsy had a 5-year freedom from biochemical failure of 40% versus 76% for patients with a negative biopsy (P = 0.0003). Univariate and multivariate analysis found that risk group, HT, and implant dose significantly affected biopsy outcome. Patients with low risk features (prostate specific antigen [PSA] 10 ng/mL or Gleason score >/= 7 or classification T2b or higher) (n = 164) (P = 0.008). Hormonal therapy was associated with a negative biopsy rate of 98% versus 84% for implant alone (P = 0.003). Patients receiving a high implant dose (D90 >/= 140 grays [Gy] for (125)I or >/= 100 Gy for (103)Pd) (n = 174) had a negative biopsy rate of 95% versus 77% for those receiving a low dose (D90 < 140 Gy for (125)I or < 100 Gy for (103)Pd) (n = 87; P < 0.001). CONCLUSIONS: Biopsy results support the use of brachytherapy without external beam irradiation for patients with low risk features and highlight the importance of achieving an adequate implant dose.

Biopsy results after real-time ultrasound-guided transperineal implants for stage T1-T2 prostate cancer.

PURPOSE: To analyze the results of ultrasound-guided brachytherapy for stage T1-T2 prostate cancer, as shown by biopsy results. PATIENTS AND METHODS: The 268 patients (mean age 66 years; range 41-83 years) underwent real-time ultrasound-guided implantation of either iodine-125 (N = 186) or palladium-103 (N = 82) seeds. Of these patients, 96 (36%) received total androgen suppression for 3 months prior to and 3 months after implantation. Prostate biopsy was performed 24 months later, with the six to eight cores all being interpreted by the same pathologist. Each specimen was rated either positive or negative for cancer. RESULTS: Of the 268 patients, 238 (89%) had a negative biopsy at 24 months. Among the patients receiving androgen suppression, 2% were found to have positive biopsies compared with 16% of those not given hormones (P = 0.004). Of the 155 patients with stage T1-T(2a) cancer, 6% had a positive biopsy compared with 19% of patients with stage T(2b) or T(2c) cancer (P = 0.001). In the entire series, the pretreatment serum concentration of prostate specific antigen, Gleason score, and isotope (I v Pd) were not significant predictors of a positive biopsy. However, among the 172 patients who did not receive androgen suppression, all three factors were predictive: 42% for Gleason score of 7 to 10 v 13% for Gleason score < or =6 (P = 0.001): 25% for pretreatment PSA concentration >10 ng/mL v 13% for PSA < or = 10 ng/mL (P = 0.05); and 27% for stage T(2b) or T(2c) v 9% for stage T1 or T(2a) (P = 0.001). The isotope used and the last PSA value were not significant predictors. CONCLUSION: Brachytherapy provides excellent local control of prostate cancer, with 89% of patients having negative biopsies 2 years after treatment. High-risk patients may benefit from the addition of androgen suppression.

Use of artificial neural networks in the clinical staging of prostate cancer: implications for prostate brachytherapy.

PURPOSE: This review describes two studies to evaluate artificial neural networks (ANNs) in prostate cancer staging. In the first study, an ANN was trained to identify prostate cancer patients at low risk of lymph node spread (LNS). The second study evaluated an ANN to predict capsular penetration (CP) in men with clinically localized prostate cancer. An accurate assessment of lymph node status will help identify those brachytherapy patients in whom lymphadenectomy can be avoided. The accurate prediction of CP can help determine the appropriateness of brachytherapy as a treatment option. MATERIALS AND METHODS: An ANN to predict LNS was trained and tested using a database from one institution (n = 4,133) and validated using two databases (n = 330 and n = 227) from different institutions. The clinical variables used were clinical stage (cTNM), Gleason sum, and prostate-specific antigen concentration (PSA). The ANN to predict CP was trained and validated with data from a single institution (n = 409). The variables used were age, race, PSA, PSA velocity, Gleason sum, and cTNM. RESULTS: The LNS ANN was able classify 76%, 75%, and 30% of the patients in each database as being at low risk of LNS with 98% accuracy. The CP ANN correctly identified CP in 25 (84%) of patients and produced 5 (16%) false-negative predictions. CONCLUSIONS: These preliminary results suggest that ANNs can be useful in staging prostate cancer. If sufficiently accurate ANNs can be developed and tested, they have the potential to increase the accuracy of clinical staging and thus improve treatment decisions.

Intraoperative dosimetric representation of the real-time ultrasound-guided prostate implant.

PURPOSE: To describe a method of creating an intraoperative dosimetric representation of the real-time ultrasound-guided prostate implant. MATERIALS AND METHODS: An intraoperative dosimetry system (Multi Media Systems [MMS]) captures transverse ultrasound images after peripheral needles have been implanted in the prostate. The prostate contour and needle positions are outlined on the system. The volume of the prostate with needles in place is calculated. As seeds are deposited in the actual implant, the positions of the seeds are marked on the intraoperative system. Following implantation of the peripheral needles, the resulting isodose lines are displayed. The interior needles are inserted into the prostate, and these positions are captured on the system. As seeds are deposited through these needles into the prostate, their positions are captured on the planning system. When the implant is complete, the final dose coverage and dose volume histogram can be visualized. RESULTS: Ten consecutive patients underwent iodine 125 implants using real-time intraoperative isodose generation. The ratio of the preneedle prostate volume to postneedle prostate volume ranged from 0.89 to 1.0 (median 0.97). The calculated dose delivered to 90% of the prostate volume from the dose volume histogram (D90) ranged from 146.5 to 194 Gy (median 174.75 Gy). The percentage of the prostate covered by 240 Gy ranged from 14.6% to 59% (median 40.75%). CONCLUSION: Dosimetric representation of the real-time ultrasound-guided prostate implant can be achieved and demonstrates the efficacy of this brachytherapy technique.

Dynamic cystography can replace cystoscopy following prostate seed implantation.

PURPOSE: To determine if dynamic cystography can replace cystoscopy following prostate seed implantation. MATERIALS AND METHODS: Three hundred three consecutive patients underwent prostate seed implantation using the real-time method. Following implantation, 60 cc of contrast media was injected into the bladder using continuous fluoroscopy. If any seed motion was detected, cystoscopy was performed and any seeds encountered were removed. Patients were followed after discharge for any seeds passed in the urine. RESULTS: Of the 303 patients, 3 (1%) were found to have one or more seeds in the bladder. No patients passed seeds following discharge. There were no adverse events associated with the cystography. CONCLUSION: Dynamic cystography can replace cystoscopy as the postimplant study to evaluated misplaced intravesical or urethral seeds.

Prior transurethral resection does not increase morbidity following real-time ultrasound-guided prostate seed implantation.

PURPOSE: Patients with localized prostate cancer who had a prior open prostatectomy or transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) may be at risk for greater morbidity when treated with brachytherapy. This analysis examines the morbidity following brachytherapy using the real-time method to determine if patients with a history of TURP are at increase risk for developing complications. MATERIALS AND METHODS: An ultrasound-guided transperineal interactive prostate seed was implanted in 419 patients with T1-T2 prostate cancer. All patients were implanted using a peripheral weighting of sources (75%) with the interior sources placed at least 5 mm from the urethra. The patients were divided into two groups: group 1 consisted of 376 patients (89.7%) without a prior TURP, and group 2 consisted of 43 patients (10.3%) who had a TURP prior to their implant. The mean age, prostate-specific antigen level, Gleason score, clinical stage, prostate volume, isotope implanted, and number of patients treated with neoadjuvant hormone therapy were comparable for both groups. RESULTS: Median follow-up for group 1 was 12 months and for group 2 was 18 months. No patients suffered from radiation-related proctitis or cystitis in either group of patients. Two patients in group 2 implanted with iodine 125 and who had a history of two prior TURPs developed mild superficial urethral necrosis (SUN). The actuarial freedom from developing superficial urethral necrosis at 4 years was 84% in patients with a history of prior TURP. There were no episodes of SUN in group 1 and no cases of incontinence reported in either group of patients. The actuarial rate of potency was 78% at 2 years. CONCLUSION: Whereas other techniques of seed implantation report incontinence in patients who had a prior open prostatectomy or TURP, the real-time method combined with peripheral loading avoids this complication.

Use of radioimmunoscintigraphy with indium-111-labeled CYT-356 (ProstaScint) scan for evaluation of patients for salvage brachytherapy.

PURPOSE: Indium 111 capromab pendetide radioimmunoscintigraphy (ProstaScint) has been used to detect occult recurrent carcinoma after radical prostatectomy. MATERIALS AND METHODS: We evaluated the role of ProstaScint in 24 men with rising prostate-specific antigen (PSA) level following definitive radiation therapy to differentiate between local and distant recurrence in this patient population. RESULTS: ProstaScint scan detected prostatic uptake only in 16 patients, extraprostatic uptake in 5, both prostatic and extraprostatic uptake in 1, and no uptake in 2. Ten of 21 patients with prostatic uptake had positive biopsies, 5 had negative biopsies, and 6 were not biopsied. Two of the three patients with negative scans had positive biopsies, and the third patient was not biopsied. Three patients had evidence of osseous metastasis on radionuclide bone scan, two corresponding to the sites detected on ProstaScint. All three patients had abnormal uptake beyond the prostatic fossa with (n =2) or without (n = 1) prostatic uptake. There were no positive bone scans in patients without extraprostatic uptake on ProstaScint. CONCLUSIONS: ProstaScint scan is useful in detecting occult recurrence outside the prostate in patients with rising PSA following radiation therapy. Compared to data from radical prostatectomy, ProstaScint scans in these patients reveal a higher prevalence of abnormal uptake in the prostate and less frequent extraprostatic uptake.