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Purpose: A large prostate has been found to correlate with improved prostate cancer survival in men undergoing radical prostatectomy. In the current study we analyzed the relationship of prostate size and prostate specific antigen (PSA) failure in men undergoing brachytherapy for localized prostate cancer., Materials and Methods: We studied data on 613 men who had undergone I radioactive seed implantation. Average patient age +/- SD was 65 +/- 7.2 years. Average prostate volume ultrasonically measured at seed insertion was 40 +/- 15 ml. All patients had a minimum of 2 years of followup., Results: Men with a large prostate had increased freedom from failure compared to men with a small prostate. Failure time in men with an intermediate size prostate was between that for large and small prostates. This difference in failure rates was significant (log rank test p = 0.0002). We further analyzed our data with Cox regression. Large prostate size significantly correlated with increased time to PSA failure (p = 0.013) and it was independent of the significant effects of Gleason score, PSA, disease stage (p <0.001), minimal radiation dose covering 90% of prostate volume (p = 0.008) and hormone treatment, including androgen ablation (p = 0.001)., Conclusions: Some investigators have postulated that paracrine signals acting to regulate epithelial proliferation in benign prostatic hypertrophy have beneficial influences on coexistent prostate cancer. Our finding that the effect of prostate size is independent of Gleason score, PSA and disease stage supports the paracrine signal mechanism. If a circulating substance, such as a cytokine, might be responsible for improved survival, this substance might be useful for treating prostate cancer. Moreover, since we found that prostate size is independent of PSA, Gleason score and tumor stage for predicting outcome, we hypothesize that patients with a small prostate treated with brachytherapy might benefit from hormone treatment and larger radiation doses. These measures are now generally reserved for men with more advanced tumors, higher PSA and increased Gleason scores.

Purpose: To evaluate, in a retrospective review, prostate brachytherapy dosimetry outcomes relative to the transurethral resection of the prostate (TURP) cavity size to address the theoretical concern that an intraprostatic cavity may hinder adequate radioactive source placement., Methods and Materials: A total of 73 patients who underwent prostate brachytherapy as part of their treatment of localized prostate cancer had a history of a prior TURP. Of these 73 patients, 37 underwent (125)I implantation, 19 (103)Pd implantation, and 17 partial (103)Pd implantation. The dose was calculated using the dose to 90% of the prostate gland (D(90)) from the 1-month post-implant dosimetric analysis. The doses were normalized relative to 100% of the prescription dose. Archived transrectal ultrasound images were used to determine the maximal length and width of the visible residual TURP cavities. The prolate spheroid or symmetric egg shape was used to calculate each residual cavity volume. The derived volume of the TURP cavity was divided by the measured ultrasound volume of the prostate at brachytherapy, creating a percentage of volume measurement for each prostate. All p values, unless otherwise specified, were generated by comparing patients without a visible TURP defect with the subgroups of patients with a visible defect using the Student t test., Results: A visible residual TURP defect was noted on the operative transrectal ultrasound images of 55 (75%) of the 73 patients with a history of TURP before brachytherapy. The 18 patients without a visible TURP defect had a median D(90) of 96% and were used for subsequent statistical comparison. Thirty-six patients with a TURP defect <10% of the entire prostate volume had a median D(90) of 109% (p = 0.02). Thirteen patients with a TURP defect between 10% and 20% of the prostate volume had a median D(90) of 112% (p = 0.03). Six patients with a TURP defect >20% of the prostate volume had a D(90) of 89% (p = 0.43)., Conclusion: A visible residual TURP cavity that is assumed to have a prolate spheroid shape and occupy >/=10% of a prostate volume did not appear to be a statistically significant hindrance to proper dosimetric outcome.

Purpose: The efficacy of a multimodality protocol using neoadjuvant and concomitant hormonal therapy, brachytherapy, and three-dimensional conformal external beam radiotherapy (RT) in high-risk prostate cancer was evaluated using biochemical outcomes and posttreatment biopsy results., Methods and Materials: Between February 1994 and November 1999, 132 high-risk patients were treated with combined hormonal therapy (9 months), permanent radioactive seed brachytherapy, and external beam RT, with follow-up ranging from 36 to 88 months (median, 50 months). The eligibility criteria were any of the following: Gleason score 8-10, initial prostate-specific antigen (PSA) level >20 ng/mL, clinical Stage T2c-T3, or positive seminal vesicle biopsy, or two or more of the following: Gleason score 7, PSA level >10-20 ng/mL, or Stage T2b. Twenty percent of patients had a positive seminal vesicle biopsy before therapy. Negative laparoscopic pelvic lymph node dissections were performed in 44% of patients., Results: The actuarial overall freedom from PSA failure rate was 86% at 5 years. The freedom from PSA failure rate at 5 years was 97% for those with a Gleason score of < or =6 (35 of 36), 85% for a Gleason score of 7 (50 of 59), and 76% for a Gleason score of 8-10 (28 of 37; p = 0.03). A trend was noted toward worse outcomes in seminal vesicle biopsy-positive patients, with a 5-year freedom from PSA failure rate of 74% vs. 89% for all other patients (p = 0.06). Posttreatment prostate biopsies were performed in 47 patients and were negative in 96% at the first biopsy and 100% at the last biopsy., Conclusion: Trimodality therapy with androgen suppression, brachytherapy, and external beam RT for high-risk prostate cancer results in excellent biochemical and pathologically confirmed local control.

Purpose: Achieving a minimal dose of 140 Gy to 90% of the prostate (D90) on postimplant dosimetry has been shown to yield improved biochemical control by 125I brachytherapy, and a D90 >180 Gy can be associated with increased long-term toxicity of seed implantation. Significant enlargement of the prostate on postimplant CT compared with the ultrasound (US) volume at implantation (CT/US ratio) has been associated with lower dose results, but other factors predicting for high or low doses are not well established. We determined whether the prostate size at implantation influenced the CT/US ratio results affecting postimplant dosimetry or predicted for D90 values <140 or >180 Gy in patients implanted with 125I in a community hospital setting., Methods and Materials: The dosimetry results from 501 patients from 33 community hospitals were analyzed after full dose 125I implantation. Implant radioactivity was obtained from reference tables relating millicuries to prostate volume (PV). Seeds were placed under real-time US guidance with peripheral weighting in a uniform method for all prostate sizes. CT-based dosimetry was performed 1 month after implantation. Dose-volume histogram parameters were analyzed for volume effects, including D90, the dose to 10% and 30% of the rectal wall, and the dose to 30% of the urethra and bladder. The PV was defined as small (<25 cm3), medium (25 to <40 cm3), or large (> or =40 cm3)., Results: The PV ranged from 9 to 79 cm3 (median 32.7). A D90 > or =140 Gy was achieved in 452 patients (90%). The median D90 was 164 Gy (range 90-230) and increased from 149.5 Gy in small prostates to 164 Gy in medium (p <0.001) and 176 Gy in large (p <0.001) prostates. A D90 <140 Gy occurred in 20% of small vs. 9% of medium and 3% of large prostates (p = 0.003). A D90 >180 Gy occurred in 7% of small and 10% of medium vs. 25% of large glands (p <0.001). The rectal dose increased significantly with an enlarging PV. The bladder and urethral doses increased from the small to medium PVs, although did not increase further in the large glands. The median CT/US ratios showed a significant volume relationship, decreasing with enlarging PVs, but were not associated with a D90 <140 or >140 Gy. The D90 results for <140 Gy and >140 Gy occurred at equal activities per volume., Conclusion: Ninety percent of patients implanted by community-level practitioners using reference tables and real-time US-guided implantation achieved a D90 outcome of > or =140 Gy. Significant differences in dose outcomes <140 Gy and >180 Gy occurred related to PV. Those with prostates <25 cm3 had a 20% frequency of D90 <140 Gy, unrelated to excessive postimplant volume enlargement or insufficient activity per reference table, suggesting that the activity-to-volume recommendations may not allow for much variance in final seed position. Such seed displacement may contribute to lower doses, most commonly in small glands. One may consider increasing the activity implanted in small prostates, because a D90 >180 Gy occurred in only 7% of these cases. Patients with glands >40 cm3 were 25% likely to have a D90 result >180 Gy and were at only 3% risk of a D90 <140 Gy. These patients may benefit from intraoperative dosimetry or a reduction in implant activity.

Purpose: Although acute urinary morbidity after prostate brachytherapy has been well-documented, long-term effects have not been fully characterized. We describe a late complication of I-125 prostate brachytherapy we have termed urinary symptom flare., Methods and Materials: A total of 172 patients who underwent I-125 prostate brachytherapy between 1991 and 1998 completed a pretreatment and at least four follow-up International Prostate Symptom Score (IPSS) forms. Follow-up visits were made 1 month after implant and at 3- to 6-month intervals thereafter. Follow-up periods ranged from 12 to 106 months (median 41.5 months). The number of IPSS forms per patient ranged from 4 to 17 (median 6). A total of 32.6% of patients received both 3 months of neoadjuvant and 3 months of adjuvant hormonal therapy. Postimplant dosimetry revealed D90 values of 5578-25692 cGy (median 17290 cGy). The peak voiding score, indicating the time of the most severe urinary morbidity after brachytherapy, was defined as the highest rise in IPSS recorded after implantation. The nadir score was the lowest IPSS attained after the peak score, generally indicating a return to the patient's preimplant urinary function. A "flare" was defined as a rise in IPSS from the nadir score of at least five points, denoting a late exacerbation of urinary symptoms. Patients with a transient rise in PSA of 0.1 ng/ml or greater were considered to have a PSA bounce., Results: The mean pretreatment IPSS for the study population was 7.5. The mean peak IPSS was 19.4 and occurred from 0.1 to 25 months (median 1.3 months) after the date of implant. The mean nadir IPSS was 6.7 and occurred from 1.6 to 61.6 months (median 14.3) after brachytherapy. A total of 35.5% of patients (61/172) have experienced a urinary flare of 5 or more points, as measured by the IPSS form. The mean "flare" IPSS was 16.4. The time to develop a flare ranged from 5.8 to 64 months (median 23.9 months). The actuarial risk of developing a flare was 21% by 2 years, 34% by 3 years, 38% by 4 years, and 47% by five years. In 72% of patients (44/61) who developed a flare, the flare subsided to baseline by the next follow-up visit. Of the remaining patients, 3% (2/61) reached a baseline value two follow-up visits later. In 25% of the patients (15/61) who experienced a flare, it occurred during their last follow-up visit. No single factor, including PSA (p = 0.9), stage (p = 0.9), use of hormone therapy (p = 0.9), implanted activity (p = 0.1), ultrasound volume (p = 0.4), dose (p = 0.4), seed number (p = 0.4), or needle number (p = 0.9), had a significant effect on the risk of developing a flare. There was a trend for younger patients (65, p = 0.07) to experience the urinary flare., Conclusions: Acute symptoms after I-125 prostate brachytherapy appear to peak 1 month after a prostate implant and return to their baseline values at 1 year. A transient late exacerbation of urinary symptoms is common and can occur in up to half of all patients by 5 years. There appears to be no statistically significant association between a late exacerbation in urinary symptoms and clinical or implant parameters.

Purpose: To calculate the actuarial risk of developing a prostate-specific antigen (PSA) bounce after prostate brachytherapy alone, using three definitions of bounce mentioned in the literature, and to explore the relationship between disease and treatment variables and the risk of developing a bounce. The impact of PSA bounce on PSA failure was also explored., Methods and Materials: A total of 373 patients with T1-T2 prostate cancer underwent radioactive seed implant using 125I (n = 337) or 103Pd (n = 36) without hormonal therapy or external beam RT. All patients had a minimum of 1 year (median 4, maximum 11) of follow-up and at least three follow-up PSA values. PSA bounce was defined by a rise of one or two PSA values with a subsequent fall. Three definitions of bounce were used: definition 1, rise > or = 0.1 ng/mL; definition 2, rise > or = 0.4 ng/mL; and definition 3, rise >35% of previous value., Results: The actuarial likelihood of experiencing a PSA bounce at 5 years was 31% for definition 1, 17% for definition 2, and 20% for definition 3. The median time to develop a bounce was 19.5 months for definitions 1 and 2 and 20.5 months for definition 3. Gleason score, initial PSA level, and clinical stage did not predict for bounce using any definition. Using definition 1, younger patients (< or = 65 years) had a bounce rate at 5 years of 38% vs. 24% for older patients (p = 0.009). 125I patients receiving an implant dose of < or = 160 Gy had a bounce rate (definition 1) at 5 years of 24% vs. 38% for those receiving a dose delivered to 90% of the gland on the 1 month postimplant dose-volume histogram (D90) >160 Gy (p = 0.04). Using definition 2, prostate volume significantly affected the incidence of bounce. Patients with larger glands (>35 cm(3)) were more likely to experience a bounce (23% at 5 years) than those with smaller glands (< or = 35 cm(3)) who had a bounce rate of 11% at 5 years (p = 0.01). In a multivariate analysis of factors predicting for PSA failure, PSA bounce was not found to be significant., Conclusion: PSA bounce is a common phenomenon after prostate brachytherapy and occurs at a rate of 17-31%, depending on the definition used. It is more common in younger patients, those receiving higher implant doses, and those with larger glands. PSA bounce does not predict for future PSA failure.

Prostate brachytherapy has become an accepted treatment modality for localized prostate cancer. Long-term biochemical and biopsy data confirm the early positive impressions that brachytherapy is as valid a treatment option as radical prostatectomy or EBRT. Quality-of-life data also look promising, but more follow-up data are needed. Is brachytherapy as good as or perhaps better than radical prostatectomy? This question cannot be answered yet. Well-controlled, randomized studies are needed. In the meantime, the clinician will have to rely on the available published data.

Purpose: The risk of developing any cancer in carriers of the I1307K mutation of the adenopolyposis coli (APC) gene is significantly increased (odds ratio 1.5, P = 0.01). One of the cancers associated with the I1307K mutation is prostate cancer (odds ratio 2.0, P = 0.14). Also, there is an association of APC mutations with thyroid cancer. In this study, we measured triiodothyronine (t3) levels in Ashkenazi Jewish prostate cancer patients, with and without the I1307K mutation of the APC gene., Materials and Methods: Participants in our study were found through urology and radiation oncology clinics in 1999 and 2000. All eligible patients were asked to take part. All patients had been initially diagnosed on the basis of rising PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Ethnic background was confirmed for all subjects by self-report or interview. The I1307K allele of the APC gene was detected by amplification of DNA isolated from peripheral blood according to standard polymerase chain reaction (PCR) and dot blot procedures. Serum t3 level was determined by fluorescent immunoassay with a standard, commercially available instrument., Results: We studied 77 patients. The youngest patient was 46, the oldest 88, average age 67 +/- 7.2 (mean +/- SD). Eleven males carrying the APCI 1307K allele had significantly higher serum t3 levels than 66 males carrying the wild type allele. There were no homozygotes for the I1307K allele. None of the males had a t3 level that was above the normal range for our laboratory (137 ng/dl)., Conclusions: Our findings of increased serum t3 level with the APC I1307K allele in prostate cancer patients is not surprising, given the mitogenic potential of t3. Further studies may clarify whether t3 elevation is the mechanism whereby APC gene mutations increase the risk of prostate cancer, or whether other pathophysiologic abnormalities are involved.

Purpose: Prostate brachytherapy has been reported to have less morbidity for patients than radical prostatectomy or external beam irradiation. However, to date there have been no long-term data to support these claims. With radiation doses in excess of 140 Gy required to control the tumor, disabling chronic urinary symptoms and associated quality of life (QOL) changes might be expected to occur. This study prospectively assessed the long-term effects of (125)I prostate brachytherapy on urinary morbidity., Methods and Materials: A total of 248 patients with a median age of 67 years (range, 43-83 years) who presented with T1-T2 prostate cancer were treated with (125)I seed implantation and followed up for a minimum of 18 months after treatment (range, 18 to 108 months; median, 31 months). There were 177 T1b-T2a cases and 41 patients with prostate-specific antigen >10 ng/ml; 20.2% were treated with hormonal therapy. All patients prospectively reported their urinary symptoms and QOL assessment on American Urological Association symptom score records before treatment and at each follow-up visit. Urinary symptoms at last follow-up were compared with pretreatment scores. Radiation doses to the prostate (dose delivered to 90% of the gland; D(90)) and urethra (D(30)) were determined by CT-based dosimetry., Results: The median prostate D(90) was 165 Gy (range, 16.5-260 Gy), and the median urethra D(30) was 192 Gy (range, 23.5-306 Gy). Mean individual scores and QOL ranged from 0.31 to 1.65 before implantation and 0.39 to 1.73 afterward. There were no significant differences between pretreatment and last mean scores for any of the categories except for a small but significant increase in urgency (p=0.01) and weak stream (p=0.03). The cohort of patients who initially presented with marked urinary symptoms (initial score >or=3) had improvement in individual scores by 31.4% to 58.2%, total score by 31.1% (p=0.0005), and QOL by 40.6% (p<0.0001)., Conclusions: This study suggests that prostate brachytherapy is associated with minimal long-term urinary morbidity. The subgroup of patients who present with marked urinary symptoms before implantation has improvement in symptoms and QOL after implantation. These data substantiate the favorable long-term QOL outcomes associated with modern brachytherapy techniques.

Purpose: To compare the results of intraoperative dosimetry with those of CT-based postimplant dosimetry in patients undergoing prostate seed implantation., Methods and Materials: Seventy-seven patients with T1-T3 prostate cancer received an ultrasound-guided permanent seed implant (36 received (125)I, 7 (103)Pd, and 34 a partial (103)Pd implant plus external beam radiation therapy). The implantation was augmented with an intraoperative dosimetric planning system. After the peripheral needles were placed, 5-mm axial images were acquired into the treatment planning system. Soft tissue structures (prostate, urethra, and rectum) were contoured, and exact needle positions were registered. Seeds were placed with an applicator, and their positions were entered into the planning system. The dose distributions for the implant were calculated after interior needle and seed placement. Postimplant dosimetry was performed 1 month later on the basis of CT imaging. Prostate and urethral doses were compared, by using paired t tests, for the real-time dosimetry in the operating room (OR) and the postimplant dosimetry., Results: The mean preimplant prostate volume was 39.8 cm(3), the postneedle planning volume was 41.5 cm(3) (p<0.001), and the 1-month CT volume was 43.6 cm(3) (p<0.001). The mean difference between the OR dose received by 90% of the prostate (D(90)) and the CT D(90) was 3.4% (95% confidence interval, 2.5-6.6%; p=0.034). The mean dose to 30% of the urethra was 120% of prescription in the OR and 138% on CT. The mean difference was 18% (95% confidence interval, 13-24%; p<0.001)., Conclusions: Although small differences exist between the OR and CT dosimetry results, these data suggest that this intraoperative implant dosimetric representation system provides a close match to the actual delivered doses. These data support the use of this system to modify the implant during surgery to achieve more consistent dosimetry results.

Unlabelled: Triiodothyronine is the active thyroid hormone produced by de-iodination of the precursor thyroxine that is necessary for the growth of prostate cancer cells in vitro. For this reason we assessed serum triiodothyronine levels in men with localized prostate cancer, benign prostatic hyperplasia (BPH) and controls in the same age group., Materials and Methods: We studied 161 men referred for treatment of localized prostate cancer, 20 with BPH and 27 controls. Serum triiodothyronine was determined by fluorometric immunoassay and a commercially available instrument., Results: Men with BPH had the highest triiodothyronine levels, followed by those with prostate cancer. Controls had the lowest triiodothyronine. There was significant triiodothyronine variation among the 3 groups (1-way ANOVA p = 0.001). In men with BPH serum triiodothyronine was significantly different from that in men with prostate cancer (Tukey's multiple range test p = 0.013). Men with prostate cancer had serum triiodothyronine that was significantly different than in controls (p = 0.048), as did those with BPH (p <0.001). Because serum triiodothyronine normally decreases with age, we performed multivariate analysis of variance controlling for age. There was a significant decrease in serum triiodothyronine with age (p = 0.020). There was also significant triiodothyronine variation among the 3 subject groups independent of age (p <0.001)., Conclusions: 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. With more and better biomarkers many older men with prostate cancer may be spared the rigors of radiation therapy and/or surgery as well as complications. Triiodothyronine may be such a biomarker. Also, new prostate cancer and BPH therapies may be directed toward inhibiting the mitogenic effects of triiodothyronine.

Prostate brachytherapy has become a popular treatment option for localized prostate cancer with over 44,000 procedures performed in 2000. Eighty-seven percent to 93% of patients who have a serum prostate-specific antigen less than 10 ng/mL, Gleason score of 6 or less, and low risk (disease stage < or = T2a) can be expected to have an 8 to 10 year disease-free rate. The radiation dose delivered by the implants should exceed 140 Gy in men implanted with I-125 monotherapy. Patients with intermediate- and high-risk prostate cancer would benefit from the addition of either hormonal therapy and/or external beam irradiation to the implantation of seeds. Postimplant incontinence and proctitis can be minimized by controlling high radiation doses to the urethra and rectum. Potency is preserved in 70% of men with good preimplantation erectile function. Advances in technology, such as intraoperative dosimetry, will continue to make brachytherapy an attractive treatment option for men with localized prostate cancer.

Objective: Post-implant dosimetry has become the gold standard for implant evaluation and it is recommended that it be performed on all patients undergoing prostate brachytherapy. The technique, results and correlation with clinical outcomes will be presented., Methods: The method and outcomes of post-implant dosimetry are explored by outlining the experience at the Mount Sinai Medical Center, New York, as well as reviewing the literature. The most accurate time to perform post-implant dosimetry is 1 month after implant. Computed tomography (CT)-based dosimetry is currently the best available technique for performing this analysis. The technique involves taking 3-mm abutting CT slices throughout the implanted area. The prostate and normal structures are outline on the CT slices. These structures are recreated in three dimensions. Dose volume histograms (DVH) are created and allow the dose to these organs to be quantified., Results: The relationship between dosimetric findings and clinical outcomes has been established. The dose delivered to 90% of the prostate on DVH (D90) has been correlated to prostate-specific antigen (PCA) control and post-treatment biopsy results. D90 values of >or=140Gy have been associated with improved biochemical control and lower positive post-treatment biopsy results. Doses derived from the dosimetric analysis to prostate, urethra and rectum have been correlated with the development of acute and chronic urinary morbidity, sexual potency and rectal morbidity. Future initiatives involve performing dosimetric calculations intraoperatively at the time of the implant., Conclusions: Post-implant CT-based dosimetry is an essential component of prostate brachytherapy. It is the only method of assessing the actual dose delivered to the prostate and normal surrounding structures. Future development in post-implant and intraoperative dosimetry will continue to improve permanent prostate brachytherapy as a safe an effective treatment for prostate cancer.

Unlabelled: We assessed the relationship of American Urological Association (AUA) urinary symptom score and tumor stage in men treated for localized prostate cancer., Methods: 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 PSA or abnormal physical examination. Histological confirmation of diagnosis was obtained for all subjects. Tumor stage was determined by digital rectal examination. 265 men with prostate cancer were studied., Results: There was a significant difference in AUA symptom score in the three disease stages (p = 0.035, one way anova). Tukey's multiple range B test showed a significant difference between the AUA symptom scores of patients with t3 disease, when compared to patients with t1 and t2 disease (p = 0.05). The range test showed no significant difference between the AUA symptom scores of patients with t1 and t2 disease (p = 0.897). There was a significant difference in mean age of men with t1, t2, and t3 disease (p < 0.001). Men with t2 disease had a mean age of 69 years, as opposed to men with t1 and t3 disease (mean ages 66 and 64, respectively). Tukey's multiple range B test showed a significant difference (p = 0.05) between the ages of the men with t2 disease and the men with t1 or t3 disease. But there was no significant difference between the ages of the men with t1 and t3 disease. There was no relationship between age and AUA symptom score (r = 0.008, P = 0.89). The AUA symptom score index classifies the symptoms of men with a score of 0 to 7 as mild, 8 to 19 moderate, and 20 and above as severe. According to this classification, 55.6% of the prostate cancer patients we studied had mild symptoms, 37.1% had intermediate symptoms, and 7.3% had severe symptoms., Conclusions: The majority (approximately 80%) of prostate cancers are found in the peripheral zone. But prostate cancers associated with urinary symptoms might arise in the periurethral transition zone, where almost all symptomatic benign prostatic hypertrophy originates. We hypothesize that symptomatic and non-symptomatic prostate cancer may be two distinct disease entities, each with its own characteristic genetic complement. In addition, urologists are actively seeking additional indicators 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 AUA symptom score and outcome would be worthwhile. If AUA symptom score is a predictor of outcome that is independent of t stage, AUA score might be clinically valuable in disease management.

Purpose: To study the impact of hormonal therapy (HTx) on intermediate- to high-risk prostate cancer treated with permanent radioactive seed implantation., Methods and Materials: Patients with Stage T1b-T3bN0 prostate cancer, and Gleason score > or = 7 or prostate-specific antigen (PSA) level >10 ng/mL were treated with seed implantation with or without HTx. Their disease was defined as intermediate risk (PSA 10-20, Gleason score 7, or Stage T2b) or high risk (two or more intermediate criteria, or PSA >20 ng/mL, Gleason score 8-10, or Stage T2c-T3). The median follow-up for 201 eligible patients was 42 months (range 18-110). Biochemical failure was defined as a rising PSA >1.0 ng/mL. Pretreatment disease characteristics, implant dose, and HTx were evaluated using univariate and multivariate analyses., Results: HTx significantly improved 5-year actuarial freedom from biochemical failure rate, 79% vs. 54% without HTx. In addition, high-dose, PSA < or = 15 ng/mL, intermediate risk, and Stage T2a or lower significantly improved outcome in the univariate analyses. HTx was the most significant predictor of 5-year actuarial freedom from biochemical failure (p <0.0001) in a multivariate analysis. The best outcome was in the intermediate-risk patients treated with a high implant dose and HTx, resulting in a 4-year actuarial freedom from biochemical failure rate of 94%., Conclusion: In this retrospective review, HTx improved outcome in intermediate- to high-risk prostate cancer patients treated with brachytherapy. HTx was the most important prognostic factor in the univariate and multivariate analyses.

Purpose: To define the optimal dose for 125I prostate implants by correlating post implant CT dosimetry findings with urinary symptoms, biochemical failure, and posttreatment biopsies., Methods and Materials: Patients with T1-T2, Gleason score 2-6 prostate cancer treated with I-125 brachytherapy were analyzed. Group 1 (276 patients) was observed from 18 to 108 months (median, 34 months) and had urinary symptoms prospectively assessed using the International Prostate Symptom Score (IPSS) system. Group 2 (181 patients) observed from 24 to 108 months (median, 44 months) and did not receive hormonal therapy. Implant dose was defined as the D90 (dose delivered to 90% of the prostate on a dose-volume histogram). Patients were analyzed by dose categories: <140 Gy, 140 to <160 Gy, 160 to <180 Gy, and > or =180 Gy. In Group 1, the mean pre- to postimplant IPSS scores were compared in different dose categories by using a matched paired t test. In Group 2, the effect of dose on biochemical control was tested with actuarial methods by using the American Society for Therapeutic Radiology and Oncology definition and on local control with posttreatment biopsies (113 patients)., Results: A comparison of pre- with postimplant IPSS revealed no significant changes in scores in the dose groups <180 Gy except for small changes in urgency and bladder emptying in the dose group <140 Gy. In dose group >180 Gy, mean scores changed from 0.5 to 1.0 (p=0.002) for emptying, 0.76 to 1.29 (p=0.004) for weak stream, 0.24 to 0.51 (p=0.009) for straining, 1.55 to 1.82 (p=0.05) for nocturia, and 6.3 to 8.45 (p=0.0009) for the total score. Freedom from biochemical failure (FFBF) at 5 years was 68% for doses <140 Gy, 97% for 140 to <160 Gy, 98% for 160 to <180 Gy, and 95% for > or =180 Gy (p=0.0025). Overall, patients with doses <140 Gy (median follow-up, 66 months) had an FFBF of 68%, compared with 96% for patients with doses > or =140 Gy (median follow-up, 35 months; p=0.0002). Multivariate analysis found dose to be the most significant factor affecting FFBF. Positive biopsies were found in 23% for doses <140 Gy, 21% for 140 to <160 Gy, 10% for 160 to <180 Gy, and 8% for > or =180 Gy. Overall, biopsies were positive in 22% for doses <160 Gy vs. 9% for > or =160 Gy (p=0.05)., Conclusions: Optimal 125I prostate implants should deliver a D90 of 140-180 Gy, on the basis of postimplant dosimetry. Doses of <140 Gy are associated with increased biochemical failure, and doses >180 Gy with a small increase in long-term urinary symptoms.

Purpose: Standard therapies for locally advanced prostate cancer have resulted in suboptimal disease control rates. A Phase I/II trial was designed for patients with positive seminal vesicle biopsies, prostate-specific antigen (PSA) >15 ng/ml, Gleason score > or =8 or clinical classification T2c-T3 to improve local control and to test the tolerance of the prostate to high-dose radiation by using neoadjuvant hormonal therapy, 103Pd brachytherapy, and conformal three-dimensional external beam radiation therapy (EBRT). This article outlines treatment-related morbidity and PSA response to this regimen and analyzes the effect of escalating doses of brachytherapy., Methods and Materials: Forth-three patients with T1c-T3 prostate cancer were enrolled in a Phase I/II trial from March 1994 through September 1997. Follow-up ranged from 12 to 64 months (median, 32 months). Pretreatment PSA ranged from 2.1 to 202 ng/ml (median, 16 ng/ml). Seventy-seven percent (33 of 43) of patients had high-grade tumors (score > or =7). Seventy-four percent (32 of 43) had stage > or =T2c. A total of 21 (49%) patients had positive seminal vesicle biopsies. Treatment consisted of hormonal therapy for 3 months with leuprolide and flutamide followed by a 103Pd implant and, 2 months later, 59.4 Gy of three-dimensional EBRT. Hormonal therapy was continued for 9 months. The planned 103Pd dose was escalated from 57 Gy (13 patients) to 77 Gy (13 patients) to 86 Gy (17 patients)., Results: The actuarial freedom from PSA failure (PSA>0.5 ng/ml) at 4 years was 74%. There were no significant differences found when analyzing patients by presenting PSA or seminal vesicle status. There was a trend toward improved outcome with higher doses delivered to the prostate via the implant. Patients receiving doses > or =65 Gy (31 patients) had a freedom from PSA failure rate at 4 years of 89.5%, compared with 52.5% for those receiving doses <65 Gy (10 patients; p=0.08). The last PSA values for those patients free from PSA failure were < or =0.1 ng/ml in 25 (69%), >0.1-0.2 ng/ml in 5 (14%), and >0.2-0.5 ng/ml in 6 (17%). The actuarial freedom from developing Grade 2 proctitis was 75% at 4 years. There was a trend toward increased proctitis with increasing prostate implant doses. Patients with doses < or =70 Gy (n=12) had a 92% freedom from Grade 2 proctitis compared with 67.5% for those with doses delivered to 90% of the gland from a dose-volume histogram of >70 Gy (n=29) (p=0.15). There were no cases of Grade 3 or 4 proctitis. The 3-year actuarial preservation of sexual potency rate was 43%., Conclusions: The preliminary results from this regimen show an improvement in PSA control for this group of locally advanced prostate cancer patients over more standard therapies. To maximize control while minimizing toxicity, doses of 65-70 Gy of 103Pd should be used when 59.4 Gy of three-dimensional EBRT is delivered. Longer follow-up will be needed to further substantiate these findings.

Purpose: To determine the extent of edge and gland position changes caused by needle insertion in patients undergoing prostate brachytherapy., Methods and Materials: Nineteen patients with T1-T3 prostate cancer were implanted with the real-time method by using a two-phase peripheral loading technique. Serial contours of the prostate at 5-mm intervals were acquired by the dose-planning system. All of the peripheral needles were then placed and spaced 5-10 mm apart by using the largest transverse ultrasound image as the reference plane. The position of the probe was relocated at the zero plane, and the difference between the preneedle and postneedle zero plane was recorded as the difference in the z axis. Axial ultrasound images were again acquired. The second set of captured images, which matched in number the first set, was contoured over the previously contoured preneedle images. Prostate gland deformation and displacement were determined by comparing the preneedle contoured image with the images captured after needle placement. Deformation was determined by calculating the differences between the edges of the gland as measured at the major axis of the gland (x and y planes). Displacement was determined by measuring the differences between the center positions of the two contoured structures. Deformation and displacement were determined on each acquired 5-mm image. Differences were compared by student's t test., Results: The mean preneedle prostate volume was 47 ml (range, 21.5-68.7 ml), compared with 48.1 ml (range, 19.4-80.3 ml; p = 0.228) after peripheral needle placement. A median of 16 (range, 12-19) peripheral needles were placed. The median change in the base position of the prostate was 1.5 cm (range of 0 to 3.0 cm; p = 0.0034). The mean x and y deformation was 6.8 mm (median, 7.9 mm; range, 4.3-8.1 mm) and 3.6 mm (median, 3.3 mm; range, 1.0-5.5 mm), respectively. The greatest deformation for any individual slice for x was 21.6 mm and for y was 15.3 mm. The mean number of slices that were found with a >2-, 5-, and 10-mm deformation in the x axis was 7 (range, 3-10), 4 (range, 1-3), and 1 (range, 0-4), respectively. Similar deformation in the y axis was found in 6 (range, 3-10), 2.5 (range, 0-6), and 0.3 (range, 0-2) slices. The mean x and y displacement was 1.9 mm (median, 1.8 mm; range, 0.3-6.6 mm) and 2.8 mm (median, 1.9 mm; range, 2-5.8 mm). The greatest displacement for any individual slice for x was 7 mm and for y was 10 mm. The mean number of slices with a displacement >2, 5, and 10 mm in the x axis was 5 (range, 1-10), 0.8 (range, 0-5), and 0, respectively. Similar displacement in the y axis was found in 5 (range, 0-9), 1.7 (range, 0-7), and 0 slices, respectively., Conclusions: Placing most needles in the periphery results in a minimal prostate volume increase, suggesting little need to overplan the implant when this method is used. However, significant edge and gland position changes caused by the needle insertion did occur. These changes may explain some of the difficulty in reproducing the preplan and should be taken into consideration for all types of prostate brachytherapy planning.

Background: In the present study, we assessed the relationship of serum insulin levels and risk of recurrence in men with localized prostate cancer because of the relationship of insulin to the development of prostate cancer, and because insulin is a growth factor., Methods: 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 (Immulite Diagnostic Products Corporation, Los Angeles, CA). Patients were divided into three risk groups: Low risk: serum PSA < or = 10, stage < or = T2a, or Gleason grade < or = 6; Medium risk: serum PSA 10-15, Gleason 7 or stage < or = T2b; High risk: Gleason > 7, tumor in seminal vesicle biopsy, serum PSA > 15 or stage T2c or T3., Results: Men, 112 in number, with prostate cancer were studied. There was a significant increase in serum insulin with risk group (P = 0.002, 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., Conclusions: 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 now impossible to identify such tumors with certainty. Further studies of serum insulin levels in prostate cancer as a biomarker might, therefore, be worthwhile. With more and better biomarkers, many older men might be spared the rigors of radiation therapy and/or surgery, and their complications. Also, new prostate cancer therapies might be directed toward inhibiting the mitogenic effects of insulin., (Copyright 2002 Wiley-Liss, Inc.)