Wayne M. Butler

American Brachytherapy Society consensus guidelines for transrectal ultrasound-guided permanent prostate brachytherapy

PURPOSE To provide updated American Brachytherapy Society (ABS) guidelines for transrectal ultrasound-guided transperineal interstitial permanent prostate brachytherapy (PPB). METHODS AND MATERIALS The ABS formed a committee of brachytherapists and researchers experienced in the clinical practice of PPB to formulate updated guidelines for this technique. Sources of input for these guidelines included prior published guidelines, clinical trials, published literature, and experience of the committee. The recommendations of the committee were reviewed and approved by the Board of Directors of the ABS. RESULTS Patients with high probability of organ-confined disease or limited extraprostatic extension are considered appropriate candidates for PPB monotherapy. Low-risk patients may be treated with PPB alone without the need for supplemental external beam radiotherapy. High-risk patients should receive supplemental external beam radiotherapy if PPB is used. Intermediate-risk patients should be considered on an individual case basis. Intermediate-risk patients with favorable features may appropriately be treated with PPB monotherapy but results from confirmatory clinical trials are pending. Computed tomography-based postimplant dosimetry performed within 60 days of the implant is considered essential for maintenance of a satisfactory quality assurance program. Postimplant computed tomography-magnetic resonance image fusion is viewed as useful, but not mandatory. CONCLUSIONS Updated guidelines for patient selection, workup, treatment, postimplant dosimetry, and followup are provided. These recommendations are intended to be advisory in nature with the ultimate responsibility for the care of the patients resting with the treating physicians.

Performance of transperineal template-guided mapping biopsy in detecting prostate cancer in the initial and repeat biopsy setting

Transrectal ultrasound (TRUS) biopsy can miss 20–30% of clinically significant cancers. We evaluate an alternative approach—transperineal template-guided mapping biopsy (TTMB) in the initial and repeat biopsy setting. From January 2005 through September 2008, 373 consecutive men underwent TTMB (294 men with ⩾1 prior negative biopsy and 79 men as the initial biopsy). The location of each positive biopsy core, number of positive cores, and percent involvement of each core was recorded. Cancer detection rate for the initial biopsy was 75.9%. For men with 1, 2, and ⩾3 prior negative biopsies detection rates were 55.5%, 41.7%, and 34.4%, respectively. In all, 55.5% of the cancers identified were Gleason ⩾7. The majority of the cancers were multifocal. There was no significant change in the number of positive cores or Gleason score as the number of prior biopsies increased. The anterior and apical aspects of the prostate were among the most common cancer locations. TTMB provides a high rate of cancer detection as initial and repeat biopsy. TTMB was particularly effective at diagnosing anterior and apical cancer. TTMB may have particular application for men considering active surveillance, with prior negative TRUS biopsies, and those considering subtotal gland or other minimally invasive treatments.

Temporal resolution of urinary morbidity following prostate brachytherapy

PURPOSE To report the short-term urinary morbidity for prostate brachytherapy patients without a preimplant history of a transurethral resection of the prostate gland and who received prophylactic and prolonged alpha-blockers. alpha-blockers may decrease radiation-induced urethritis and increase urinary flow. Multiple clinical and treatment parameters were evaluated to identify factors associated with increased acute urinary morbidity. MATERIALS AND METHODS One hundred seventy consecutive patients without a prior history of a transurethral resection of the prostate gland underwent transperineal ultrasound guided prostate brachytherapy for clinical T1c-T3a carcinoma of the prostate gland. For all patients, an alpha-blocker was initiated prior to implantation and continued at least until the international prostate symptom score (IPSS) returned to baseline levels. Clinical parameters evaluated for short-term urinary morbidity included patient age, clinical T stage, preimplant IPSS (obtained within 3 weeks of implantation), and prostate ultrasound volume. Treatment parameters included the utilization of neoadjuvant hormonal manipulation, the utilization of moderate dose external beam radiation therapy before implantation, the choice of isotope, the urethral dose, the total implant activity in millicuries, and a variety of dosimetric quality indicators (D(90) and V(100)/V(150)/V(200)). Catheter dependency and the duration of alpha-blocker dependency was also evaluated. On average, 11.2 IPSS surveys were obtained for each patient. RESULTS One hundred fifty of the 170 patients (88.2%) had the urinary catheter permanently removed on day 0. Only one patient required an urinary catheter for > 5 days. Two patients (1.2%) required a subsequent transurethral resection of the prostate gland because of prolonged obstructive/irritative symptoms. To date, no patient has developed an urinary stricture or urinary incontinence. The IPS score on average peaked at 2 weeks following implantation. This score returned to within 1 point of the antecedent value at a median of 6 weeks and a mean of 13.3 weeks. At 26 and 50 weeks, 85% and 56% of the patients, respectively, continued with alpha-blockers. Of the clinical and treatment parameters evaluated for short-term urinary morbidity, only variants of the IPSS such as the maximum, maximum increase, and preimplant IPSS values correlated with time to return to the referent zone with p < 0.05. CONCLUSION The return of the IPS score to baseline occurred more rapidly in our series than what has previously been reported. The 1.2% incidence of transurethral resections also compares favorably with the published literature. We believe these results may be due to maintaining the average urethral dose to approximately 115% of the prescribed dose and the prophylactic and long-term use of alpha-blockers.

AAPM recommendations on dose prescription and reporting methods for permanent interstitial brachytherapy for prostate cancer: Report of Task Group 137

During the past decade, permanent radioactive source implantation of the prostate has become the standard of care for selected prostate cancer patients, and the techniques for implantation have evolved in many different forms. Although most implants use I125 or P103d sources, clinical use of C131s sources has also recently been introduced. These sources produce different dose distributions and irradiate the tumors at different dose rates. Ultrasound was used originally to guide the planning and implantation of sources in the tumor. More recently, CT and/or MR are used routinely in many clinics for dose evaluation and planning. Several investigators reported that the tumor volumes and target volumes delineated from ultrasound, CT, and MR can vary substantially because of the inherent differences in these imaging modalities. It has also been reported that these volumes depend critically on the time of imaging after the implant. Many clinics, in particular those using intraoperative implantation, perform imaging only on the day of the implant. Because the effects of edema caused by surgical trauma can vary from one patient to another and resolve at different rates, the timing of imaging for dosimetry evaluation can have a profound effect on the dose reported (to have been delivered), i.e., for the same implant (same dose delivered), CT at different timing can yield different doses reported. Also, many different loading patterns and margins around the tumor volumes have been used, and these may lead to variations in the dose delivered. In this report, the current literature on these issues is reviewed, and the impact of these issues on the radiobiological response is estimated. The radiobiological models for the biological equivalent dose (BED) are reviewed. Starting with the BED model for acute single doses, the models for fractionated doses, continuous low-dose-rate irradiation, and both homogeneous and inhomogeneous dose distributions, as well as tumor cure probability models, are reviewed. Based on these developments in literature, the AAPM recommends guidelines for dose prescription from a physics perspective for routine patient treatment, clinical trials, and for treatment planning software developers. The authors continue to follow the current recommendations on using D90 and V100 as the primary quantities, with more specific guidelines on the use of the imaging modalities and the timing of the imaging. The AAPM recommends that the postimplant evaluation should be performed at the optimum time for specific radionuclides. In addition, they encourage the use of a radiobiological model with a specific set of parameters to facilitate relative comparisons of treatment plans reported by different institutions using different loading patterns or radionuclides.

Supplement to the 2004 Update of the AAPM Task Group No. 43 Report

Since publication of the 2004 update to the American Association of Physicists in Medicine (AAPM) Task Group No. 43 Report (TG-43U1), several new low-energy photon-emitting brachytherapy sources have become available. Many of these sources have satisfied the AAPM prerequisites for routine clinical use as of January 10, 2005, and are posted on the Joint AAPM/RPC Brachytherapy Seed Registry. Consequently, the AAPM has prepared this supplement to the 2004 AAPM TG-43 update. This paper presents the AAPM-approved consensus datasets for these sources, and includes the following 125I sources: Amersham model 6733, Draximage model LS-1, Implant Sciences model 3500, IBt model 1251L, IsoAid model IAI-125A, Mentor model SL-125/ SH-125, and SourceTech Medical model STM1251. The Best Medical model 2335 103Pd source is also included. While the methodology used to determine these data sets is identical to that published in the AAPM TG-43U1 report, additional information and discussion are presented here on some questions that arose since the publication of the TG-43U1 report. Specifically, details of interpolation and extrapolation methods are described further, new methodologies are recommended, and example calculations are provided. Despite these changes, additions, and clarifications, the overall methodology, the procedures for developing consensus data sets, and the dose calculation formalism largely remain the same as in the TG-43U1 report. Thus, the AAPM recommends that the consensus data sets and resultant source-specific dose-rate distributions included in this supplement be adopted by all end users for clinical treatment planning of low-energy photon-emitting brachytherapy sources. Adoption of these recommendations may result in changes to patient dose calculations, and these changes should be carefully evaluated and reviewed with the radiation oncologist prior to implementation of the current protocol.

Seed fixity in the prostate/periprostatic region following brachytherapy

PURPOSE Although postoperative dosimetric analyses of prostate brachytherapy are commonly reported, the long-term persistence, or fixity, of seeds implanted in the prostate gland and periprostatic region remains unclear, with only a few reports regarding the loss or migration of the seeds in the implanted region and none which correlate lung embolization to pelvic seed loss. METHODS AND MATERIALS The study population consisted of 175 consecutive patients implanted with either 125I (95 patients) or 103Pd (80 patients) using a mean of 136 seeds in a modified uniform loading approach to cover a planning volume that was 1.64 times the ultrasound prostate volume. An average of 64% of 125I seeds were embedded in braided vicryl suture, and these seeds were used on the periphery and extra prostatic regions. Following CT-based dosimetric analysis on day 0, all patients had orthogonal plain films of the pelvis obtained from day 0 to day 502, with an average of 2.3 film pairs per patient. Routine diagnostic PA and lateral chest X rays were obtained for 156 patients over the same time period. RESULTS The mean pelvic seed fixity was greater than 98% throughout the time covered by this study. The seed fixity rates for 125I and 103Pd, although nearly equal, were significantly different up to 60 days post implant. The median 125I seed loss per patient was only 1 seed through 180 days while for 103Pd, the median seed loss was 2 seeds at 28 and 60 days and 3 seeds at 180 days. The fraction of patients experiencing no seed loss decreased from 40% at 28 days to 20% at 180 days for 125I and from 24% to 7% for 103Pd over the same time interval. Patient and treatment parameters closely correlated to local seed loss include the number of seeds implanted, the planning volume, and the number of loose seeds, and for 125I, the fraction of seeds in suture. The fraction of seeds placed outside the gland was not correlated with seed loss. Of the seeds lost from the pelvis, about 10% were found to embolize to the lungs. Among the 156 patients with post-implant chest X rays, the fraction of patients with pulmonary seed embolization was 34/156 (21.8%). Of the 20 patients who had post-implant chest X rays obtained within 14 days of brachytherapy, none had seeds detected in the lungs, while of the 136 patients who had chest X rays obtained greater than 30 days following implantation, 25.0% (34 patients) were noted to have seeds visualized in the lungs. CONCLUSIONS With a median follow-up of 9 months, 125I seeds embedded in a vicryl suture or 103Pd seeds can be safely implanted in the prostate and periprostatic tissue with a high probability of prostate bed seed fixity and a low incidence of radioactive seed embolization to the lungs.

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.

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.

Long-term urinary quality of life after permanent prostate brachytherapy

PURPOSE To evaluate late urinary function after permanent prostate brachytherapy using a validated, patient-administered quality-of-life instrument. METHODS AND MATERIALS A total of 225 consecutive patients underwent prostate brachytherapy between April 1995 and March 1998. Of the 225 patients, 17 had died and 3 had been institutionalized secondary to Alzheimers disease. Of the remaining 205 patients, each was mailed a self-administered questionnaire (the urinary function component of the Expanded Prostate Cancer Index [EPIC] and the International Prostate Symptom Score [IPSS]). Of the 205 surveys mailed, 195 (95.1%) were returned. The mean and median follow-up was 66.3 and 64.0 months, respectively. The clinical parameters evaluated included age, pretreatment prostate-specific antigen level, Gleason score, stage, risk group, prostate volume, presence of diabetes and hypertension, and tobacco consumption. The treatment parameters included the ultrasound planning volume, hormonal status, use of supplemental external beam radiotherapy, isotope, and follow-up. The dosimetric parameters included values of the minimal dose received by 90% of the prostate gland and the percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose. Because detailed baseline urinary function was not available, a cross-sectional survey was performed in which 51 newly diagnosed prostate cancer patients of comparable demographics served as controls. RESULTS When the survey scores for the implant patients were compared with the control group, no significant differences in either the IPSS or function, bother, incontinence, or irritation/obstruction subscales of the urinary EPIC were discernible. In addition, no significant difference was observed between the implant and control groups when the EPIC and IPSS surveys were evaluated by each individual question. Of all the evaluated parameters, the use of tobacco was the best predictive variable for diminished quality of life. CONCLUSION No significant difference was noted in the overall long-term urinary quality of life when brachytherapy patients were compared with a group of newly diagnosed prostate cancer patients of comparable demographics. Of all parameters evaluated, tobacco consumption was the single strongest predictor of late urinary function.

Long-Term Outcome for Clinically Localized Prostate Cancer Treated With Permanent Interstitial Brachytherapy

PURPOSE To present the largest series of prostate cancer brachytherapy patients treated with modern brachytherapy techniques and postimplant day 0 dosimetric evaluation. METHODS AND MATERIALS Between April 1995 and July 2006, 1,656 consecutive patients were treated with permanent interstitial brachytherapy. Risk group stratification was carried out according to the Mt. Sinai guidelines. Median follow-up was 7.0 years. The median day 0 minimum dose covering at least 90% of the target volume was 118.8% of the prescription dose. Cause of death was determined for each deceased patient. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on the evaluated survival parameters. RESULTS At 12 years, biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) for the entire cohort was 95.6%, 98.2%, and 72.6%, respectively. For low-, intermediate-, and high-risk patients, bPFS was 98.6%, 96.5%, and 90.5%; CSS was 99.8%, 99.3%, and 95.2%; and OS was 77.5%, 71.1%, and 69.2%, respectively. For biochemically controlled patients, the median posttreatment prostate-specific antigen (PSA) concentration was 0.02 ng/ml. bPFS was most closely related to percent positive biopsy specimens and risk group, while Gleason score was the strongest predictor of CSS. OS was best predicted by patient age, hypertension, diabetes, and tobacco use. At 12 years, biochemical failure and cause-specific mortality were 1.8% and 0.2%, 5.1% and 2.1%, and 10.4% and 7.1% for Gleason scores 5 to 6 and 7 and ≥8, respectively. CONCLUSIONS Excellent long-term outcomes are achievable with high-quality brachytherapy for low-, intermediate-, and high-risk patients. These results compare favorably to alternative treatment modalities including radical prostatectomy.