Management of sexual dysfunction after prostate brachytherapy

Erectile dysfunction is a common sequela following potentially curative local treatment for early-stage carcinoma of the prostate gland. With larger studies and longer follow-up, it is clear that erectile dysfunction following prostate brachytherapy is more common than previously reported, with a myriad of previously unrecognized sexual symptoms. Approximately 50% of patients develop erectile dysfunction within 5 years of implantation. Several factors including preimplant potency, patient age, the use of supplemental external-beam irradiation, radiation dose to the prostate gland, radiation dose to the bulb of the penis, and diabetes mellitus appear to exacerbate brachytherapy-related erectile dysfunction. The majority of patients with brachytherapy-induced erectile dysfunction respond favorably to sildenafil citrate (Viagra). Despite reports questioning the potency-sparing advantage associated with brachytherapy, recent elucidations of brachytherapy-related erectile dysfunction may result in refinement of treatment techniques, an increased likelihood of potency preservation, and ultimately, improved quality of life.     

Short-term sexual function after prostate brachytherapy

Sexual function was evaluated in 34 patients with low-risk prostate cancer (PSA < or = 10, Gleason score < or = 6, clinical stage T1/T2) undergoing brachytherapy in a phase III prospective randomized trial comparing iodine-125 ((125)I) to palladium-103 ((103)Pd). The mean and median International Index of Erectile Function (IIEF) scores for the entire group were 14.2 and 16.5, respectively, and there was no difference between these scores when stratified by isotope. IIEF scores < 6, 6 to 11, and > or = 12 were recorded in 35% (12/34), 6% (2/34), and 59% (20/34) of patients, respectively. Hematospermia, orgasmalgia (pain at the time of orgasm), and alteration in intensity of orgasm were documented in 26% (9/34), 15% (5/34), and 38% (13/34) of patients, respectively, but these side effects were of limited duration for most patients. There was no relationship between radiation dose to the neurovascular bundles (NVB), which averaged 209% of the prescribed prostate dose, and the development of postbrachytherapy impotence. All four impotent patients who used sildenafil responded favorably. With a median follow-up of 13 months, 65% of patients undergoing prostate brachytherapy maintained sexual function without pharmacologic support. Including sildenafil responses, 76.5% of patients sustained erections sufficient for sexual intercourse.     

Potential role of various dosimetric quality indicators in prostate brachytherapy.

PURPOSE: Postoperative CT-based dosimetric analysis provides detailed information regarding the coverage and uniformity of an implant, but the assessment of implant quality remains an unanswered and controversial issue. There is no disagreement that a good implant should cover the target volume with an adequate dose, but there is no consensus as to what represents an adequate dose. MATERIALS AND METHODS: The American Brachytherapy Society has recently proposed that prostate brachytherapy quality be measured in terms of the following parameters: D90, V100, and V150 where D90 is defined as the minimal dose covering 90% of the prostate volume and V100 and V150 are defined as the percent volume of the prostate receiving at least 100% or 150% of the prescribed minimal peripheral dose (mPD), respectively. We report detailed day 0 dosimetric evaluation for 60 consecutive prostate brachytherapy patients implanted via a standard transperineal ultrasound guided approach in terms of D90, D100, V90, V100, and V150 and also the maximal and average rectal and urethral dose. RESULTS: Dosimetric evaluation resulted in a V100 greater than 80% of the prostate volume and a D90 greater than 90% of the mPD in the entire patient population. There was a statistically significant difference between the quality scores of 125I implants and 103Pd implants with the 125I mean V100 and D90 at 95.3% volume and 109.9% mPD, respectively, vs. 103Pd at 91.8% volume and 103.7% mPD. Likewise, the rectal and urethral doses as a fraction of mPD were significantly lower in 103Pd than in 125I implants. This occurred despite the fact that palladium implants were typically preplanned with significantly better coverage and hotter V150 than iodine implants. We consider V150 to be an important parameter for determining dose homogeneity although the clinical utility of dose homogeneity remains unknown. The mean V150 was 45.6 +/- 9.6% volume. There was no additional dosimetric utility from a determination of V90 while D100 was found to be overly sensitive to steep dose gradients at the periphery of the prostate. CONCLUSIONS: This report represents the first detailed postimplant day 0 dosimetric evaluation comparing ABS recommended quality parameters used to evaluate prostate brachytherapy. At the present time, no long-term clinical outcomes are available because of short follow-up. As PSA based follow-up data becomes available, however, this report may help define what represents an adequate implant.     

A comparison of radiation dose to the bulb of the penis in men with and without prostate brachytherapy-induced erectile dysfunction

PURPOSE: To retrospectively evaluate the relationship between the radiation dose to the bulb of the penis and the development of erectile dysfunction (ED) in patients undergoing permanent prostate brachytherapy without external beam radiation therapy. METHODS AND MATERIALS: Twenty-three men who developed ED after transperineal ultrasound-guided permanent prostate brachytherapy for clinical T1/T2 adenocarcinoma of the prostate gland were paired with 23 similar men who maintained potency after implantation. Potency was defined as an erection sufficient for vaginal penetration. The mean and median follow-up for the entire group was 34.6 +/- 13.7 months and 32.8 months, respectively. Patients were implanted with either (125)I (145 Gy TG-43) or (103)Pd (115 Gy, pre-NIST-99). No patient received external beam radiation therapy either before or after brachytherapy. The bulb of the penis was outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis was defined in terms of the minimal dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)). RESULTS: The radiation dose delivered to the bulb of the penis in men with postbrachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Multivariate analysis indicated that dose to the bulb of the penis and patient age at the time of implant were predictive of postimplant ED, whereas choice of isotope had no effect. Among potent patients, 19/23 had D(50) < or = 40% of prescribed minimal peripheral dose, whereas for the impotent patients, 19/23 had D(50) >40% of the minimal peripheral dose. Of the impotent patients, 17 utilized sildenafil, with 15 experiencing a favorable response (88%). CONCLUSION: Our data suggest that prostate brachytherapy-induced impotence is highly correlated with the radiation dose delivered to the bulb of the penis. With Day 0 dosimetric evaluation, the radiation dose delivered to 50% of the bulb of the penis should be maintained at 50 Gy or less to maximize post-treatment potency. Fortunately, the majority of the brachytherapy-induced ED population responds favorably to sildenafil.     

The dosimetry of prostate brachytherapy-induced urethral strictures

PURPOSE: There is a paucity of data regarding the incidence of urethral strictures after prostate brachytherapy. In this study, we evaluate multiple clinical, treatment, and dosimetric parameters to identify factors associated with the development of brachytherapy-induced urethral strictures. METHODS AND MATERIALS: 425 patients underwent transperineal ultrasound-guided prostate brachytherapy using either (103)Pd or (125)I for clinical T1b/T3a NxM0 (1997, American Joint Committee on Cancer) adenocarcinoma of the prostate gland from April 1995 to October 1999. No patient was lost to follow-up. 221 patients were implanted with (103)Pd and 204 patients with (125)I. The median patient age was 68 years (range 48-81 years). The median follow-up was 35.2 months (range 15-72 months). Follow-up was calculated from the day of implantation. Thirteen patients developed brachytherapy-induced strictures, and all strictures involved the membranous urethra. A control group of 35 patients was rigorously matched to the stricture patients in terms of treatment approach; i.e., choice of isotope, plus or minus radiation therapy, and plus or minus hormonal manipulation. Nine of the 13 stricture patients had detailed Day 0 urethral dosimetry available for review. The apex of the prostate gland and the membranous urethra were defined by CT evaluation. Urethral dosimetry was reported for the prostatic urethra, the apical slice of the prostate gland, and the membranous urethra which was defined as extending 20 mm in length. RESULTS: The 5-year actuarial risk of a urethral stricture was 5.3%, with a median time to development of 26.6 months (range 7.8-44.1 months). Of multiple clinical and treatment parameters evaluated, only the duration of hormonal manipulation (>4 months, p = 0.011) was predictive for the development of a urethral stricture. The radiation dose to the membranous urethra was significantly greater in patients with strictures than those without: 97.6% +/- 20.8% vs. 81.0% +/- 19.8% of prescribed minimum prostate dose, mPD (p = 0.031). The urethral dose 20 mm distal to the prostate apex was 57.6% +/- 23.8% vs. 31.5% +/- 13.9% of mPD for the stricture and control patients, respectively (p = 0.011). In addition, the extent of the 75% mPD and 50% mPD levels beyond the prostatic apex was also significantly greater for stricture patients, 16.6 +/- 5.3 mm vs. 11.9 +/- 4.5 mm (p = 0.010) and 19.0 +/- 3.2 mm vs. 16.0 +/- 3.4 mm (p = 0.021), respectively. Dose to the prostatic urethra was not predictive of stricture, but the magnitude and extent of high-dose regions within the prostate were predictive of stricture. Twelve of the 13 patients who developed urethral strictures were successfully managed by dilatation/transurethral incision. To date, 1 of the 12 patients has required a second dilatation. The remaining patient developed an iatrogenic induced injury and was catheter-dependent for 6 months. CONCLUSIONS: After prostate brachytherapy, the actuarial 5-year incidence of urethral strictures is 5.3% with a median time to development of 26.6 months. All strictures involved the membranous urethra and occurred within the first 44 months after brachytherapy. In most cases, membranous urethral strictures are easily managed with dilatation/incision. Factors predicting for the development of a urethral stricture included the magnitude and extent of high-dose regions within the prostate, the mean membranous urethra dose and the dose 20 mm distal to the prostatic apex, the maximum extent along the membranous urethra of certain dose levels, and the duration of hormonal manipulation.     

Rectal function following prostate brachytherapy

PURPOSE: Quality of life following therapeutic intervention for carcinoma of the prostate gland has not been well documented. In particular, a paucity of data has been published regarding bowel function following prostate brachytherapy. This study evaluated late bowel function in 209 consecutive prostate brachytherapy patients via a one-time questionnaire administered 16-55 months postimplant. MATERIALS AND METHODS: Two hundred nineteen consecutive patients underwent permanent prostate brachytherapy from April 1995 through February 1998 using either (125)I or (103)Pd for clinical T1c-T3a carcinoma of the prostate gland. Of the 219 patients, 7 had expired. Of the remaining 212 patients (median follow-up, 28 months), each patient was mailed a self-administered questionnaire (10 questions) with a prestamped return envelope; 209 (98.6%) surveys were returned. Clinical parameters evaluated for bowel dysfunction included patient age, diabetes, hypertension, history of tobacco consumption, clinical T-stage, elapsed time since implant, and prostate ultrasound volume. Treatment parameters included utilization of neoadjuvant hormonal manipulation, utilization of moderate dose external beam radiation therapy prior to implantation, choice of isotope ((125)I vs. (103)Pd), rectal dose (average, median and maximum doses), total implanted seed strength, values of the minimum dose received by 90% of the prostate gland (D(90)), and the percent prostate volume receiving 100%, 150%, and 200% of the prescribed minimum peripheral dose (V(100), V(150) and V(200), respectively). Because detailed baseline bowel function was not available for these patients, a cross-sectional survey was performed in which 30 newly diagnosed prostate cancer patients of comparable demographics served as controls. RESULTS: The total rectal function scores for the brachytherapy and control patients were 4.3 and 1.6, respectively, out of a total 27 points (p < 0.001). Of the evaluated clinical parameters, only the preimplant number of bowel movements per day were correlated with the total survey score (p < 0.01). None of the treatment parameters were significantly correlated with the total survey score. Despite the fact that implantation with (103)Pd resulted in lower radiation doses to the rectum, the choice of isotope was not predictive of bowel function scores. A trend toward increased rectal scores was noted for older patients, and a nonsignificant improvement in rectal survey scores was noted with elapsed time from implantation. Only 19.2% (40/208) of the treatment group reported a worsening of bowel function following implantation. Patient perception of overall rectal quality of life, however, was inversely related to the utilization of external beam radiation therapy (p = 0.034). CONCLUSION: To date, no severe changes in late bowel function have been noted following prostate brachytherapy. Although the survey scores indicate bowel function is worse after an implant, the minor changes are not significant enough to bother most individuals. Less than 20% of patients reported that their bowel function was worse following prostate brachytherapy.     

Radiation exposure to family and household members after prostate brachytherapy

PURPOSE: Patients with localized prostate cancer frequently seek alternatives to radical surgery and external beam radiation therapy. Permanent prostate brachytherapy is an acceptable option. However, fears of radiation exposure to family members may deter some individuals from choosing this treatment option. A direct measurement was performed to determine the expected lifetime exposure from the patient with a brachytherapy prostate implant to family members and the household. METHODS AND MATERIALS: After a permanent brachytherapy implant with (125)I or (103)Pd, patients and their family members were provided radiation monitors to measure direct radiation exposure at home. Each patient was given two monitors to wear, and each member of the household, including the spouse, children, and pets, was given a single monitor. In addition, four rooms in the house frequently occupied by the patient were monitored. Based on the reading from the dosimeters measured at the first follow-up visit, the lifetime exposure to each individual or room was calculated. Forty-four patients, along with their families, agreed to participate and complied with the use of the dosimeters. Twenty-nine patients received a (125)I implant and 15 a (103)Pd implant. Assays were obtained on 272 monitors: 78 worn by patients, 52 worn by household members, and 142 posted in rooms. RESULTS: Exposures measured by patient dosimeters were within the expected range for the type of implant received. Exposures to family members were low. Based on dosimeter readings, the calculated mean lifetime dose to a spouse from her husband was 0.1 (range: 0.04-0.55) mSv for a (125)I implant and 0.02 (range: 0.015-0.074) mSv for a (103)Pd implant. Other family or household members had 0.07 (range: 0.04-0.32) mSv or 0.02 (range: 0.015-0.044) mSv for (125)I and (103)Pd implants, respectively. The calculated lifetime exposure did not exceed the annual limit set by the U.S. Nuclear Regulatory Commission in any of the cases. The majority of room dosimeters (94%) had no detectable radiation exposure. CONCLUSIONS: Radiation exposure to family members from a patient receiving a permanent prostate brachytherapy implant with radioactive (125)I or (103)Pd is very low and well below the limits recommended by the U.S. Nuclear Regulatory Commission. Radiation exposure to members of a patient's family or to the public should not be a deterrent to undergoing this procedure.     

Radiation exposure after permanent prostate brachytherapy.

BACKGROUND AND PURPOSE: Limited information is available on the true radiation exposure and associated risks for the relatives of the patients submitted to prostate brachytherapy with permanent implant of radioactive sources and for any other people coming into contact with them. In order to provide appropriate information, we analyzed the radiation exposure data from 216 prostate cancer patients who underwent (125)I or (103)Pd implants at the European Institute of Oncology of Milan, Italy. PATIENTS AND METHODS: Between October 1999 and October 2004, 216 patients with low risk prostate carcinoma were treated with (125)I (200 patients) or (103)Pd (16 patients) permanent seed implantation. One day after the procedure, radiation exposure measurements around the patients were performed using an ionization chamber survey meter (Victoreen RPO-50) calibrated in dose rate at an accredited calibration center (calibration Centre SIT 104). RESULTS: The mean dose rate at the posterior skin surface (gluteal region) following (125)I implants was 41.3 microSv/h (range: 6.2-99.4 microSv/h) and following (103)Pd implants was 18.9 microSv/h (range 5.0-37.3 microSv/h). The dose rate at 50 cm from the skin decreased to the mean value of 6.4 microSv/h for the (125)I implants and to the mean value of 1.7 microSv/h for the (103)Pd implants. Total times required to reach the annual dose limit (1 mSv/year) recommended for the general population by the European Directive 96/29/Euratom and by the Italian law (Decreto Legislativo 241/2000) at a distance of 50 cm from the posterior skin surface of the implanted patient would be 7.7 and 21.6 days for (125)I and for (103)Pd. Good correlation between the measured dose rates and both the total implanted activity and the distance between the most posteriorly implanted seed and the skin surface of the patients was found. CONCLUSIONS: Our data show that the dose rates at 50 cm away from the prostate brachytherapy patients are very low and that the doses possibly absorbed by the relatives and other members of the general population coming into contact with the treated patients are well below the dose limit set by the European Directive and by the Italian regulation. However, in order to meet the recommendation of the ALARA principle (As Low As Reasonably/Readily Achievable), some advice to the patients should be given, such as to maintain a minimum distance from the patient of 1m, at least for a period equal to one half life of used radionuclide (60 days for (125)I and 15 days for (103)Pd).     

Localization of neurovascular bundles on pelvic CT and evaluation of radiation dose to structures putatively involved in erectile dysfunction after prostate brachytherapy

PURPOSE: To (a) locate neurovascular bundles (NVB) on pelvic CT and (b) retrospectively evaluate relationships between radiation dose to structures putatively involved in prostate brachytherapy-induced erectile dysfunction (ED) and incidence of postbrachytherapy ED. METHODS AND MATERIALS: (a) Right/left NVB were identified on nine prostate MRIs. Structures visible on MRI and CT were cross-referenced. Cross-sectional area of each NVB was measured. (b) All patients treated with implant alone and whose treatment was planned on Variseed (Varian Medical Systems, Palo Alto, CA), with follow-up of >12 months were included; n = 41. Median follow-up was 20 months. All patients were potent (+/- sildenafil) before implant (erection sufficient for intercourse). The right/left NVB (using results from part "a"), penile bulb, and right/left crus were outlined on postimplant CT. Volumes and doses to these structures were calculated. RESULTS: (a) On prostate MRI, NVB was consistently located where the prostate border bends away from the levator ani, at the gland's smallest radius of curvature. Average area of the circle best encompassing the NVB = 0.27 cm(2); diameter was 0.58 cm. (b) 11 of 41 (27%) patients had ED; 30 of 41 were potent (15 with sildenafil). There was no significant difference between potent/impotent patients in isotope, age, diabetes, hypertension, follow-up, or volume of prostate, bulb, right/left NVB, or right/left crus. There was a relationship between smoking and ED (p = 0.05). There was a relationship between bulb %D90 and ED: >10% 67% (4 of 6) vs. <10% 20% (7 of 35) (p = 0.03), which remained when controlling for smoking. There was no relationship between dose to left NVB and potency. There was paradoxical decreased risk of ED with right NVB %V100 >60% (p = 0.019), and right NVB %D60 >100% (p = 0.003). There was no relationship between dose to right/left crus and ED. CONCLUSIONS: A reliable method for localizing NVB on CT is demonstrated. There is no increased risk of prostate brachytherapy-induced ED with increasing dose to crus or NVB at the doses given in this study. There is a possible dose-response relationship between dose to the bulb and risk of ED.     

Dysfonctions sexuelles après irradiation pour cancer de la prostate

Sexual dysfunctions are a quality of life main concern following prostate cancer treatment. After both radiotherapy and brachytherapy, sexual function declines progressively, the onset of occurrence of erectile dysfunction being 12–18 months after both treatments. The pathophysiological pathways by which radiotherapy and brachytherapy cause erectile dysfunction are multifactorial, as patient comorbidities, arterial damage, exposure of neurovascular bundle to high levels of radiation, and radiation dose received by the corpora cavernosa at the crurae of the penis may be important in the aetiology of erectile dysfunction. Diagnosis and treatment of postradiation sexual dysfunctions must integrate pretherapeutic evaluation and information to provide to the patient and his partner a multidisciplinary sexual medicine management.     

^125I对比^103Pd治疗低危前列腺癌的系统评价

背景与目的：粒子植入近距离放射治疗是早期前列腺癌的主要治疗手段．常用核素粒子为^125I或^103Pd,二者在前列腺癌治疗的并发症和结果方面存有差异。本文用系统评价的方法分析^125I或^103Pd近距离放射治疗低危前列腺癌的疗效和副作用,为临床决策提供指导性依据。方法：采用文献检索和手工检索的方式搜集2008年5月以前有关^125I或^103Pd治疗低危前列腺癌的随机对照试验的文献资料,根据Cochrane Handbook4．2．6质量评价标准进行评价,由两位研究者交叉核对纳入试验的结果,用RevMan5．0进行统计学分析。结果：共纳入6个随机对照研究．1406例患者。^125I或^103Pd治疗低危前列腺癌生物学无进展生存率差异没有统计学意义（RR=0．97,95％CI=0．93～1．01）;治疗后1个月^103Pd组副作用较^125I组明显,治疗后6个月^125I组副作用较^103Pd明显,治疗后12个月两种核素副作用无差别。结论：使用^125I或^103Pd治疗低危前列腺癌疗效相似,副作用在治疗后不同时间点有差异。     

Erectile function after permanent prostate brachytherapy

PURPOSE: To determine the incidence of potency preservation after permanent prostate brachytherapy using a validated patient-administered questionnaire and to evaluate the effect of multiple clinical and treatment parameters on penile erectile function. MATERIALS AND METHODS: Four hundred twenty-five patients underwent permanent prostate brachytherapy from April 1995 to October 1999. Two hundred nine patients who were potent before brachytherapy and who at the time of the survey were not receiving hormonal therapy were mailed the specific erectile questions of the International Index of Erectile Function (IIEF) questionnaire with a self-addressed stamped envelope. The questionnaire consisted of 5 questions, with a maximal score of 25. Of the 209 patients, 181 (87%) completed and returned the questionnaire. The mean and median follow-up was 40.4 +/- 14.9 and 40.6 months, respectively (range 19-75). Preimplant erectile function was assigned using a three-tiered scoring system (2 = erections always or nearly always sufficient for vaginal penetration; 1 = erections sufficient for vaginal penetration but considered suboptimal; 0 = the inability to obtain erections and/or erections inadequate for vaginal penetration). Postimplant potency was defined as an IIEF score >/=11. The clinical parameters evaluated for erectile function included patient age, preimplant potency, clinical T-stage, pretreatment prostate-specific antigen level, Gleason score, elapsed time after implantation, hypertension, diabetes mellitus, and tobacco consumption. Treatment parameters included radiation dose to the prostate gland, use of hormonal manipulation, use of supplemental external beam radiotherapy (EBRT), choice of isotope, prostate volume, and planning volume. The efficacy of sildenafil citrate in brachytherapy-induced erectile dysfunction (ED) was also evaluated. RESULTS: Pretreatment erectile function scores of 2 and 1 were assigned to 125 and 56 patients, respectively. With a 6-year follow-up, 39% of patients maintained potency after prostate brachytherapy, with a plateau on the potency preservation curve. Postimplant preservation of potency (IIEF >/=11) correlated with preimplant erectile function (50.4% vs. 13.2% for preimplant scores of 2 and 1, respectively, p <0.001), patient age (57.4%, 38.2%, and 21.9% for patients <60, 60-69, and >/=70 years old, respectively, p <0.004), use of supplemental EBRT (52.0% vs. 26.4% for patients without and with EBRT, p <0.001), and a history of diabetes mellitus (41.4% vs. 0% for patients without and with diabetes, respectively, p = 0.017). In multivariate analysis, clinical stage, radiation dose to the prostate gland, hormonal manipulation, choice of isotope, history of hypertension, and tobacco consumption had no effect on the ultimate preservation of potency. Only the preimplant potency score, use of supplemental EBRT, and diabetes maintained statistical significance. Sixty-two patients used sildenafil, with 53 (85%) reporting a favorable response. When potent patients were grouped with the ED patients who used sildenafil, the 6-year actuarial rate of potency preservation was 92%. Including the 70 impotent patients who never used sildenafil, the actuarial 6-year rate of potency preservation with and without pharmacologic support was 54% and 39%, respectively. CONCLUSION: Our results suggest that brachytherapy-induced ED is more common than previously reported and may be the result of obtaining patient information by means of a validated quality-of-life instrument by mail and not by personal interview. In multivariate analysis, only pretreatment potency, supplemental EBRT, and diabetes maintained statistical significance. Most patients with brachytherapy-induced ED responded favorably to sildenafil. Although the 6-year actuarial incidence of potency preservation was 39%, 52% of patients not receiving supplemental EBRT maintained potency. In addition, with pharmacologic support, 92% of patients maintained potency.     

The importance of radiation doses to the penile bulb vs. crura in the development of postbrachytherapy erectile dysfunction

PURPOSE: Recent studies have implicated the proximal penis as a potential site-specific structure for radiation-related erectile dysfunction (ED). In this study, we evaluated by means of a validated patient-administered questionnaire whether radiation doses to the bulb of the penis and/or the proximal corporeal bodies were predictive for the development of brachytherapy-induced ED. METHODS AND MATERIALS: Thirty patients who underwent permanent prostate brachytherapy between April 1995 and October 1999 and developed brachytherapy-induced ED were paired with 30 similar men who maintained potency after implantation. None of the 60 patients received supplemental external beam radiation therapy, either before or after implantation. Potency was assessed by patient self-administration of the specific erectile questions of the International Index of Erectile Function. The questionnaire consisted of 5 questions with a maximum score of 25. Postimplant potency was defined as an International Index of Erectile Function score > or =11. Mean and median follow-up was 48.3 +/- 14.4 months and 48.0 months, respectively (range: 26.6-79.3 months). The bulb of the penis and the proximal crura were outlined at 0.5-cm intervals on the Day 0 postimplant CT scan. The radiation dose distribution to the bulb of the penis and adjacent crura was defined in terms of the minimum dose delivered to 25%, 50%, 70%, 75%, 90%, and 95% of the bulb (D(25), D(50), D(70), D(75), D(90), and D(95)). RESULTS: The radiation dose delivered to the bulb of the penis and the proximal crura in men with brachytherapy-induced ED was statistically greater for all evaluated dosimetric parameters (D(25), D(50), D(70), D(75), D(90), and D(95)). Stepwise linear regression analysis indicated that penile bulb dose parameter D(50), the postimplant prostate CT volume, and patient age at implant were predictive of postimplant ED, whereas the crura dose D(25) approached statistical significance. Seventy-five percent of the impotent men had a bulb D(25) >60% of prescribed minimum peripheral dose (mPD), whereas 80% of potent men had a bulb D(25) < or =60% mPD. Using the D(50) bulb parameter, 70% of ED men had a dose >40% mPD, whereas 90% of potent men had a dose < or =40% mPD. Similar cut points for D(25) and D(50) crura doses were 40% and 28% mPD. The crura D(25) cut point was exceeded by 50% of the ED patients and only 7% of the potent patients. CONCLUSION: This is the first study to evaluate potency preservation and radiation doses to the proximal penis by means of a validated patient-administered quality-of-life instrument. Our data confirm prior reports that radiation doses to the proximal penis are predictive of brachytherapy-induced ED. In a stepwise linear regression analysis, the strongest predictors of potency preservation were bulb D(50), postimplant prostate CT volume, and patient age. With Day 0 dosimetric evaluation, the penile bulb D(50) and D(25) should be maintained below 40% and 60% mPD, respectively, whereas the crura D(50) and D(25) should be maintained below 40% and 28% mPD, respectively, to maximize posttreatment potency.     

Sildenafil citrate (Viagra) and erectile dysfunction following external beam radiotherapy for prostate cancer: a randomized, double-blind, placebo-controlled, cross-over study

Purpose: To determine the efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction after three-dimensional conformal external beam radiotherapy (3D-CRT) for prostate cancer.

Methods and Materials: 406 patients with complaints of erectile dysfunction and who completed radiation at least 6 months before the study were approached by mail. 3D-CRT had been delivered (mean dose 68 Gy). Sixty patients were included and entered a double-blind, placebo-controlled, cross-over study lasting 12 weeks. They received during 2 weeks 50 mg of sildenafil or placebo; at Week 2 the dose was increased to 100 mg in case of unsatisfactory erectile response. At Week 6, patients crossed over to the alternative treatment. Data were collected using the International Index of Erectile Function (IIEF) questionnaire, and side effects were recorded.

Results: Mean age was 68 years. All patients completed the study. For most questions of the IIEF questionnaire there was a significant increase in mean scores from baseline with sildenafil, but not with placebo. Ninety percent of the patients needed a dose adjustment to 100 mg sildenafil. Side effects were mild or moderate.

Conclusion: Sildenafil is well tolerated and effective in improving erectile function of patients with ED after 3D-CRT for prostate cancer.     

Isotope selection for permanent prostate implants? An evaluation of 103Pd versus 125I based on radiobiological effectiveness and dosimetry

Transperineal interstitial permanent prostate brachytherapy (TIPPB) has become an increasingly popular treatment for early-stage/favorable-risk adenocarcinoma of prostate. Within TIPPB, permanent implants often use either (103)Pd (T(1/2) = 17 days) or (125)I (T(1/2) = 60 days). This review compares the radiobiological and treatment planning effectiveness of (103)Pd and (125)I implants by using the linear-quadratic model with recently published data regarding: prostate tumor cell doubling times, T(pot), alpha and alpha/beta, ratio. The tumor potential doubling times (T(pot)) were determined based on recently published proliferation constants (K(p)). The initial slope of the cell radiation dose survival curve, alpha, the terminal slope beta and the alpha/beta ratio were taken from recent published clinical and cellular results. The total dose delivered from each isotope was the dose used clinically, that is, 120 Gy for (103)Pd and 145 Gy for (125)I. Dale's modified linear-quadratic equation was used to estimate the biological effective dose, the cell-surviving fraction, the effective treatment time, and the wasted radiation dose for different values of T(pot). Treatment plans for peripherally loaded implants were compared. The T(pot) reported for organ-confined prostate carcinomas varied from 16 to 67 days. At short T(pot) both isotopes were less effective, but (103)Pd had much less dependence on T(pot) than (125)I. However, at long T(pot) both isotopes produced similar effects. The minimum surviving fraction for exposure to (103)Pd decreased from 1.40 x 10(-4) to 1.31 x 10(-5) as the T(pot) increased from 16 to 67 days. By contrast for exposure to (125)I, the minimum surviving fraction decreased from 3.98 x 10(-3) to 1.98 x 10(-5) over the same range of T(pot). A comparison of treatment plans revealed that (103)Pd plans required more needles and seeds; however, this was a function of seed strength. Both isotopes had similar dose-volume histograms for prostate, urethra, and rectum. The theoretical prediction of effectiveness using the linear quadratic equation for the common clinically prescribed total radiation doses indicated that (103)Pd should be more effective than (125)I because it had less dependence on T(pot). The greatest benefit of (103)Pd was shown to be with tumors with a short T(pot). Although the regrowth delay would be longer with (125)I, the benefit was inconsequential compared with the very slow doubling times of localized prostate cancer. Treatment planning with either isotope revealed no significant differences. These findings may explain why clinically there seemed to be no clear difference in treatment outcome with either isotope. Based on these predictions, we recommend a clinical trial to compare the efficacy of the two isotopes.     

Five-year biochemical outcome following permanent interstitial brachytherapy for clinical T1-T3 prostate cancer

PURPOSE: To evaluate 5-year biochemical disease-free outcome for men with clinical T1b-T3a NxM0 1977 American Joint Committee on Cancer (1997 AJCC) adenocarcinoma of the prostate gland who underwent transperineal ultrasound-guided permanent prostate brachytherapy. METHODS AND MATERIALS: Four hundred twenty-five patients underwent transperineal ultrasound-guided prostate brachytherapy using either 103Pd or 125I, for clinical T1b-T3a NxM0 (1997 AJCC) adenocarcinoma of the prostate gland, from April 1995 to October 1999. No patient underwent pathologic lymph-node staging. One hundred ninety patients were implanted with either 103Pd or 125I monotherapy; 235 patients received moderate-dose external beam radiation therapy (EBRT), followed by a prostate brachytherapy boost; 163 patients received neoadjuvant hormonal manipulation, in conjunction with either 103Pd or 125I monotherapy (77 patients) or in conjunction with moderate-dose EBRT and a prostate brachytherapy boost (86 patients). The median patient age was 68.0 years (range, 48.2-81.3 years). The median follow-up was 31 months (range, 11-69 months). Follow-up was calculated from the day of implantation. No patient was lost to follow-up. Biochemical disease-free survival was defined by the American Society of Therapeutic Radiation and Oncology (ASTRO) consensus definition. RESULTS: For the entire cohort, the 5-year actuarial biochemical no evidence of disease (bNED) survival rate was 94%. For patients with low-, intermediate-, and high-risk disease, the 5-year biochemical disease-free rates were 97.1%, 97.5%, and 84.4%, respectively. For hormone-naive patients, 95.7%, 96.4%, and 79.9% of patients with low-, intermediate-, and high-risk disease were free of biochemical failure. Clinical and treatment parameters predictive of biochemical outcome included: clinical stage, pretreatment prostate-specific antigen (PSA), Gleason score, risk group, age > 65 years, and neoadjuvant hormonal therapy. Isotope choice was not a statistically significant predictor of disease-free survival for any risk group. The median postimplant PSA was < or = 0.2 for all risk groups, regardless of hormonal status. The mean posttreatment PSA, however, was significantly lower for men implanted with 103Pd (0.14 ng/mL) than for those implanted with 125I (0.25 ng/mL), p < or = 0.001. CONCLUSION: With a median follow-up of 31 months, permanent prostate brachytherapy results in a high probability of actuarial 5-year biochemical disease-free survival (DFS) for patients with clinical T1b-T3a (1997 AJCC) adenocarcinoma of the prostate gland, with an apparent plateau on the PSA survival curve.     

American brachytherapy society recommendations for clinical implementation of NIST-1999 standards for (103)palladium brachytherapy. The clinical research committee of the American Brachytherapy Society

PURPOSE: Recent important developments in palladium-103 ((103)Pd) dosimetry mandate a reevaluation of (103)Pd brachytherapy prescribing practices. METHODS AND MATERIALS: The clinical research committee of the American Brachytherapy Society (ABS) convened a consensus session of brachytherapists and physicists to develop recommendations regarding future dose prescribing guidelines for National Institute of Standards and Technology (NIST-1999) calibrated (103)Pd sources. RESULTS: The ABS recommends that clinicians attempt to reproduce the implant doses delivered and reported in the literature through the past decade. CONCLUSIONS: The following should be immediately implemented for (103)Pd dosimetry: 1) All practicing physicians, physicists, dosimetrists, and suppliers implement NIST-1999 air-kerma strength standard for (103)Pd brachytherapy. 2) All treatment planning systems and dose calculation algorithms must be updated to reflect new dose rate constants. The AAPM-recommended validated value for Theraseed model 200 is 0.665 cGy h(-1) U(-1). The dose rate constant for the Mentor MED3633 seed is currently reported as 0.68 cGy h(-1) U(-1). This latter value and the values for seeds from other manufacturers are awaiting independent confirmation. 3) Physicians who previously prescribed 115 Gy for (103)Pd monotherapy prostate implants should now prescribe 125 Gy. When using (103)Pd as a boost following 45 Gy of external beam irradiation, 100 Gy should be prescribed instead of the previous 90 Gy.It is critical that all three changes be implemented concurrently, because they are interdependent.