Outcomes after prostate brachytherapy are even better than predicted.

BACKGROUND: During the first 3 years after prostate cancer treatment with radiation therapy, benign prostate-specific antigen (PSA) bounces are difficult for clinicians to distinguish from a biochemical recurrence, which can result in unnecessary interventions and erroneous predictions of outcomes. The objective of this study was to evaluate a commonly used PSA failure definition in a multinational, multi-institutional study after monotherapy with prostate brachytherapy. METHODS: Participants were selected from 2919 men who underwent permanent prostate brachytherapy at the University Medical Center Utrecht, Princess Margaret Hospital, or Seattle Prostate Institute between 1998 and 2006. Inclusion required not having received androgen-deprivation therapy and having at least 30 months of follow-up. Failure was defined as any post-treatment use of hormone therapy, clinical relapse, or prostogram-defined biochemical (PSA) failure. Cases in which the nomogram predicted biochemical failure were evaluated at each institution to verify biochemical status over time and the actual clinical outcome at 5 years. RESULTS: The median follow-up for the 1816 patients was 5.2 years. Concordance between the prostogram-predicted and actual outcomes, as measured by the Harrell c statistic, was 0.655 (95% confidence interval [CI], 0.536-0.774; P = .010) for the Princess Margaret group, 0.493 (95% CI, 0.259-0.648; P = .955) for the Seattle group, and 0.696 (95% CI, 0.648-0.744, P < .001) for the Utrecht group. The overall mean difference in biochemical recurrence-free survival at 5 years between actual outcomes and prostogram-defined outcomes was 9.2% (95% CI, 7.7%-10.6%). The total numbers of prostogram-defined and actual biochemical failures were 312 and 157, respectively (P = .001). CONCLUSIONS: The widely used prostogram could not adequately distinguish a benign PSA bounce from a biochemical recurrence after prostate brachytherapy and could not be used to counsel patients about their predicted outcomes after treatment. The authors conclude that, to avoid unnecessary active interventions after treatment, clinicians should monitor PSA levels for at least 3 years and provide reassurance to patients that a PSA rise during this time is common and may not indicate a treatment failure.

Predictors of oncological outcome after resection of locally recurrent renal cell carcinoma.

PURPOSE: Local renal cell carcinoma recurrence is rare after radical nephrectomy with curative intent. We examined our experience to describe the natural history of isolated local recurrence and characterize important prognostic factors that predict the outcome in patients treated with aggressive resection. MATERIALS AND METHODS: In an institutional database of 4,800 patients with renal cell carcinoma, of whom 2,945 underwent radical nephrectomy with curative intent, 54 were subsequently found to have isolated local recurrence in the renal fossa, ipsilateral adrenal gland or ipsilateral retroperitoneal lymph nodes, which was managed by surgical resection. In 69% of patients perioperative systemic therapy was done as an adjunct to surgical resection of local recurrence. RESULTS: Estimated median recurrence-free and cancer specific survival was 11 and 61 months, respectively. A positive surgical margin after resection of local recurrence, recurrent tumor size, sarcomatoid features in the recurrence specimen, abnormal serum alkaline phosphatase and increased lactate dehydrogenase at local recurrence were adverse risk factors associated with an increased risk of cancer specific death after resection for recurrent renal cell carcinoma. Patients with 0, 1 and greater than 1 adverse risk features demonstrated cancer specific survival times of 111, 40 and 8 months, respectively. CONCLUSIONS: Aggressive resection of isolated local recurrence offers durable local tumor control and cancer specific survival in a significant proportion of patients with renal cell carcinoma. Clinical and pathological prognostic features at local recurrence can be used for patient selection for surgery and also the thoughtful integration of systemic therapy with surgical extirpation.

Prostogram predicted brachytherapy outcomes are not universally accurate: an analysis based on the M. D. Anderson Cancer Center experience with (125)iodine brachytherapy.

PURPOSE: Many clinicians use Prostogram data to advise patients selecting prostate cancer therapy. We examined whether the Prostogram accurately predicted recurrence at 5 years in patients treated with (125)I brachytherapy at 1 tertiary cancer center. MATERIALS AND METHODS: We retrospectively reviewed the records of 208 consecutive patients with prostate cancer treated with a permanent (125)I implant without neoadjuvant androgen deprivation therapy at 1 tertiary cancer center during 1998 to 2006. In each patient the Prostogram brachytherapy formula was used to calculate 5-year biochemical recurrence-free survival probability based on clinical stage, Gleason sum score, prostate specific antigen and the receipt or not of external beam radiotherapy. Recurrence was defined as clinical relapse, death from disease, posttreatment androgen deprivation therapy, secondary treatments administered before prostate specific antigen failure or biochemical recurrence based on the Kattan modification of the American Society for Therapeutic Radiology and Oncology definition of biochemical recurrence after external beam radiation therapy. Patients were divided into quartiles based on Prostogram predicted 5-year recurrence-free survival probability and mean probability was compared to the actual 5-year recurrence-free survival rate in each quartile. Harrell's concordance statistic was used to assess the predictive accuracy of the nomogram. RESULTS: Actual 5-year biochemical recurrence-free survival rates were superior to Prostogram predicted probabilities, including 89% vs 80%, 87% vs 86%, 100% vs 89% and 100% vs 94% in quartiles 1 to 4, respectively. Harrell's concordance value was 0.487 (95% CI 0.369-0.605), indicating that the predictive accuracy of the nomogram in our patients was less than 50%. CONCLUSIONS: The Prostogram did not predict recurrence after permanent prostate brachytherapy in this series. Institutional variability requires that clinicians be cautious when using the Prostogram to counsel patients about the probability of success after permanent prostate brachytherapy.

Prospective assessment of systemic therapy followed by surgical removal of metastases in selected patients with renal cell carcinoma.

OBJECTIVE: To prospectively establish objective selection criteria for metastasectomy in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Between 1991 and 1999, 38 patients with mRCC with responsive or stable disease after initial systemic therapy, and with potentially resectable disease, were enrolled. Patients had a metastasectomy with curative intent and received consolidative adjuvant systemic therapy. RESULTS: Of the patients enrolled, 79% had stable disease after initial systemic therapy and 21% had a partial or complete response. Most (84%) had metastasectomy of one organ site. There was surgically no evidence of disease (sNED) in 76%. Operative morbidity and mortality were acceptable and 90% of the patients received adjuvant systemic therapy. The median (95% confidence interval) survival was 4.7 (3.0-7.8) years, and the median time to progression was 1.8 (0.8-3.1) years. Eight of 38 patients (21%) remained free of disease by the end of the study. Significant predictors of outcome were lack of sNED after metastasectomy, and the presence of pulmonary metastases. The median overall survival for those who had sNED was 5.6 years, vs 1.4 years for those who did not (P < 0.001). CONCLUSIONS: Metastasectomy in patients with mRCC not progressing after systemic therapy is feasible, with acceptable morbidity. Predictive factors for long-term outcome include pulmonary metastases and sNED. Future work evaluating treatments that can convert patients into surgical candidates will increase the cure rate of patients with mRCC.

Is a loose-seed nomogram still valid for prostate brachytherapy in a stranded-seed era?

PURPOSE: To characterize the amount of activity required to treat the prostate with stranded (125)I radioactive seeds and compare our stranded data with the amount of activity recommended when individual seeds are implanted using a Mick applicator. METHODS AND MATERIALS: Data from two groups of patients at The University of Texas M. D. Anderson Cancer Center who were treated with prostate brachytherapy as monotherapy were analyzed. The first group included 100 patients implanted with individual seeds in 2000 and 2001. The second group comprised 81 patients for whom stranded seeds were implanted in 2006 and 2007. Seeds in both groups were (125)I seeds with an air kerma strength of 0.497 U per seed (0.391 mCi per seed). The prescribed dose to planning target volume was 145 Gy. RESULTS: The total implanted activity and the number of seeds used were significantly lower in the second group (p < 0.0001) than in the first group. The reduction in activity in the stranded-seed group was approximately 23% for a 20-cm(3) prostate and approximately 15% for a 60-cm(3) prostate. With equivalent activity between the two groups, the stranded-seed treatment covered a larger treatment volume with the prescribed dose. CONCLUSIONS: The amount of activity required to effectively treat a prostate of a given volume was lower with stranded seeds than with loose seeds. Our experience suggests that prostate brachytherapy that uses stranded seeds leads to a more efficient implant with fewer seeds and lower overall activity, resulting in improved homogeneity.

A novel MRI marker for prostate brachytherapy.

PURPOSE: Magnetic resonance imaging (MRI) is the optimal imaging modality for the prostate and surrounding critical organ structures. However, on MRI, the titanium radioactive seeds used for brachytherapy appear as black holes (negative contrast) and cannot be accurately localized. We sought to develop an encapsulated contrast agent marker (ECAM) with high-signal intensity on MRI to permit accurate localization of radioactive seeds with MRI during and after prostate brachytherapy. METHODS AND MATERIALS: We investigated several agents with paramagnetic and superparamagnetic properties. The agents were injected into titanium, acrylic, and glass seeds, which were linked together in various combinations and imaged with MRI. The agent with the greatest T1-weighted signal was tested further in a canine prostate and agarose phantom. Studies were performed on a 1.5-T clinical MRI scanner. RESULTS: The cobalt-chloride complex contrast (C4) agent with stoichiometry (CoCl(2))(0.8)(C(2)H(5)NO(2))(0.2) had the greatest T1-weighted signal (positive contrast) with a relaxivity ratio >1 (r(2)/r(1) = 1.21 +/- 0.29). Acrylic-titanium and glass-titanium seed strands were clearly visualized with the encapsulated contrast agent marker. CONCLUSION: We have developed a novel ECAM that permits positive identification of the radioactive seeds used for prostate brachytherapy on MRI. Preclinical in vitro phantom studies and in vivo canine studies are needed to further optimize MRI sequencing techniques to facilitate MRI-based dosimetry.

A pilot trial of vascular targeted photodynamic therapy for renal tissue.

PURPOSE: Vascular targeted photodynamic therapy represents the newest generation of photodynamic therapy and a new paradigm for minimally invasive ablative therapy. We report a pilot trial of vascular targeted photodynamic therapy to evaluate the effect on porcine renal tissue. MATERIALS AND METHODS: Pigs underwent continuous infusion of WST-09 (Negma-Lerads, Toussous le Noble, France) and concurrent illumination with interstitial laser at a wavelength of 763 nm to the lower pole of the kidney. Drug doses were 0.5 to 1.0 mg/kg and light doses were 100 to 200 J. Nuclear renography was performed on postoperative day 5. On postoperative day 7 arteriography, pyelography, computerized tomography of the abdomen and necropsy were performed. RESULTS: Four of 7 animals completed therapy and all evaluations. Three animals died, including 1 of surgical complications and 2 of an anaphylactoid reaction to the Cremophor solvent in the compound. All kidneys in surviving animals functioned on nuclear renography. Renal function remained unchanged. No lesions or urine leakage was visible on imaging. On necropsy lesion size was 5 x 4 x 3 to 7 x 7 x 14 mm depending on the drug/light dose. Histology showed a distinct demarcation between the treated zone and the surrounding parenchyma at higher doses. Lesions were well demarcated with necrotic tubules, glomerular fibrinoid necrosis, capillary loop thrombosis, interstitial hemorrhage and lymphocytic infiltrates. CONCLUSIONS: Significant tissue effect with some necrosis was seen at these low drug/light combinations. This study provides the initial proof of principle that justifies further preclinical investigation of vascular targeted photodynamic therapy for renal tumors. A newer, water based formulation should decrease the incidence of reactions in swine. This newer formulation may allow further safe investigation of this novel treatment paradigm.

Surgical morbidity associated with administration of targeted molecular therapies before cytoreductive nephrectomy or resection of locally recurrent renal cell carcinoma.

PURPOSE: Targeted molecular therapies such as bevacizumab, sunitinib and sorafenib before surgical resection hold promise as rational treatment paradigms for patients with metastatic or locally recurrent renal cell carcinoma. To analyze the safety of this approach we evaluated surgical parameters and perioperative complications in patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of retroperitoneal renal cell carcinoma recurrence, and compared them to a matched patient cohort who underwent up-front surgical resection. MATERIALS AND METHODS: We evaluated surgical parameters and perioperative complications in 44 patients treated with targeted molecular therapies before cytoreductive nephrectomy or resection of local renal cell carcinoma recurrence, and in a matched cohort of 58 patients who underwent up-front surgery. RESULTS: Cohorts of patients treated with preoperative targeted molecular therapy and initial surgical resection were matched in terms of clinical characteristics, burden of metastatic disease and number of adverse prognostic factors. A total of 39 complications occurred in 17 (39%) patients treated with preoperative targeted molecular therapy and in 16 (28%) who underwent up-front resection (p = 0.287). There were no statistically significant differences in surgical parameters, incidence of perioperative mortality, re-exploration, readmission, thromboembolic, cardiovascular, pulmonary, gastrointestinal, infectious or incision related complications between patients treated with preoperative targeted molecular therapy and those who underwent up-front surgery. Duration, type and interval from targeted molecular therapy to surgical intervention were not associated with the risk of perioperative morbidity. CONCLUSIONS: Preoperative administration of targeted molecular therapies is safe, and does not increase surgical morbidity or perioperative complications in patients treated with cytoreductive nephrectomy or resection of recurrent retroperitoneal renal cell carcinoma.

Patient-reported health-related quality of life for men treated with low-dose-rate prostate brachytherapy as monotherapy with 125-iodine, 103-palladium, or 131-cesium: Results of a prospective phase II study.

PURPOSE: To compare quality of life (QoL) after brachytherapy with one of the three approved radioactive isotopes. METHODS AND MATERIALS: Patients with mostly favorable intermediate-risk prostate cancer were treated on this prospective phase II trial with brachytherapy as monotherapy, without hormonal therapy. QoL was recorded at baseline and each follow-up by using the Expanded Prostate Cancer Index Composite instrument. The minimal clinically important difference was defined as half the standard deviation of the baseline score for each domain. Mixed effect models were used to compare the different isotopes, and time-driven activity-based costing was used to compute costs. RESULTS: From 2006 to 2013, 300 patients were treated with iodine-125 (I-125, n = 98, prescribed dose [PD] = 145 Gy), palladium-103 (Pd-103, n = 102, PD = 125 Gy), or cesium-131 (Cs-131, n = 100, PD = 115 Gy). Median age was 64.9 years. Median follow-up time was 5.1 years for the entire cohort, and 7.1, 4.8 and 3.3 years for I-125, Pd-103, and Cs-131 groups, respectively. All three isotope groups showed an initial drop in QoL at first follow-up, which gradually improved over the first 2 years for urinary and bowel domains. QoL profiles were similar between I-125 and Pd-103, whereas Cs-131 showed a statistically significant decrease in QoL regarding bowel and sexual function at 12 months compared with Pd-103. However, these differences did not reach the minimal clinically important difference. Compared with I-125, the use of Pd-103 or Cs-131 resulted in cost increases of 18% and 34% respectively. CONCLUSIONS: The three different isotopes produced a similar QoL profile. Statistically significant differences favored Pd-103/I-125 over Cs-131 for bowel and sexual QoL, but this did not reach clinical significance.

Prospective Phase 2 Trial of Permanent Seed Implantation Prostate Brachytherapy for Intermediate-Risk Localized Prostate Cancer: Efficacy, Toxicity, and Quality of Life Outcomes.

PURPOSE: To report the efficacy, physician-reported toxicity, and patient-reported outcomes of men with intermediate-risk prostate cancer after brachytherapy in a prospective phase 2 trial. METHODS AND MATERIALS: This prospective phase 2 trial involved 300 patients with previously untreated prostate cancer treated from 2006 through 2013. Eligible patients had ≤cT2b (T3 excluded according to magnetic resonance imaging), Gleason score (GS) 6 with prostate-specific antigen (PSA) level 10-15 ng/mL, or GS 7 with PSA <10 ng/mL, and were treated with prostate brachytherapy (without hormonal therapy). RESULTS: Median patient age was 64.9 years; 3.7% had GS 6, 78.7% had GS 7 (3+4), and 17.7% had GS 7 (4+3). Median follow-up time was 5.1 years. Median PSA at 5 years was 0.01 ng/mL (range, 0-6.0 ng/mL). Ten biochemical failures occurred, for a 5-year freedom from biochemical failure rate of 97.3% (95% confidence interval [CI], 95.1-99.5), and 16 patients died, only 1 from prostate cancer, for 5-year rates of overall and biochemical progression-free survival of 94.9% (95% CI, 92.1-97.9) and 92.7% (95% CI, 89.3-96.2%). Four patients had late grade 3 genitourinary toxicity, and 2 patients had late grade 3 rectal toxicity; no grade 4 or 5 toxicity was observed. Rates of "moderate or big problems" at 4 years were 7.4% for urinary (vs 0.4% at baseline), 2.9% bowel (vs 0.4%), and 29.7% sexual function (vs 19.7%). Most men were "satisfied or extremely satisfied" (91% at 2 years after treatment and 93% at 4 years). CONCLUSIONS: Brachytherapy monotherapy is safe and effective and leads to good quality of life for some men with localized intermediate-risk prostate cancer.

Oncological efficacy and safety of nephron-sparing surgery for selected patients with locally advanced renal cell carcinoma.

OBJECTIVE: To evaluate perioperative complication rates, recurrence-free and cancer-specific survival (CSS) in a large group of matched patients who had nephron-sparing surgery (NSS) or radical nephrectomy (RN) for pT2-T3bN0M0 renal cell carcinoma (RCC). PATIENTS AND METHODS: With approval from the institutional review board, the institutional nephrectomy database of 3470 patients treated at the authors' institution from 1990 to 2006 was searched for patients who had NSS or RN for unilateral, sporadic, pathological T2-T3bN0M0 RCC. Patients with non-metastatic, node-negative RCC and a follow-up of >/=6 months were included in the analysis. RESULTS: In all, 601 patients treated with RN (567) or NSS (34) for pT2-T3bN0M0 RCC and a mean (median, range) follow-up of 43.4 (31.8, 6.1-172.6) and 62.1 (37.5, 7.0-192.0) months, respectively, met the study inclusion criteria. Disease recurred in four of 34 (12%) patients treated with NSS and in 164/567 (28.9%) managed with RN at a median of 24.2 and 13.2 months, respectively. There were no local recurrences among patients treated with NSS. On multivariate Cox proportional-hazards regression analysis, when adjusted for the effects of stage, grade, size and tumour histology, procedure type (NSS vs RN) was not an independent predictor of disease recurrence or RCC-specific death. Patients treated with NSS had a higher procedure-related complication rate, but similar estimated intraoperative blood loss, transfusion rate, equal duration of surgical procedure and hospital stay compared with patients managed with RN. CONCLUSION: In highly selected patients with locally advanced RCC, NSS is safe and provides oncological outcomes equivalent to patients managed with RN.

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Defining the value framework for prostate brachytherapy using patient-centered outcome metrics and time-driven activity-based costing.

PURPOSE: Value, defined as outcomes over costs, has been proposed as a measure to evaluate prostate cancer (PCa) treatments. We analyzed standardized outcomes and time-driven activity-based costing (TDABC) for prostate brachytherapy (PBT) to define a value framework. METHODS AND MATERIALS: Patients with low-risk PCa treated with low-dose-rate PBT between 1998 and 2009 were included. Outcomes were recorded according to the International Consortium for Health Outcomes Measurement standard set, which includes acute toxicity, patient-reported outcomes, and recurrence and survival outcomes. Patient-level costs to 1 year after PBT were collected using TDABC. Process mapping and radar chart analyses were conducted to visualize this value framework. RESULTS: A total of 238 men were eligible for analysis. Median age was 64 (range, 46-81). Median followup was 5 years (0.5-12.1). There were no acute Grade 3-5 complications. Expanded Prostate Cancer Index Composite 50 scores were favorable, with no clinically significant changes from baseline to last followup at 48 months for urinary incontinence/bother, bowel bother, sexual function, and vitality. Ten-year outcomes were favorable, including biochemical failure-free survival of 84.1%, metastasis-free survival 99.6%, PCa-specific survival 100%, and overall survival 88.6%. TDABC analysis demonstrated low resource utilization for PBT, with 41% and 10% of costs occurring in the operating room and with the MRI scan, respectively. The radar chart allowed direct visualization of outcomes and costs. CONCLUSIONS: We successfully created a visual framework to define the value of PBT using the International Consortium for Health Outcomes Measurement standard set and TDABC costs. PBT is associated with excellent outcomes and low costs. Widespread adoption of this methodology will enable value comparisons across providers, institutions, and treatment modalities.

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS: The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION: This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Sexual potency preservation and quality of life after prostate brachytherapy and low-dose tadalafil.

PURPOSE: To prospectively determine sexual function, bother, and potency preservation in men treated with prostate brachytherapy and twice-weekly tadalafil. METHODS AND MATERIALS: From 2005 to 2011, men treated with low-dose-rate prostate brachytherapy were treated on a prospective registration study. All patients were prescribed tadalafil 10mg twice weekly. The expanded prostate cancer index composite questionnaire was administered before treatment and at each followup. A subgroup analysis of men with sexual potency at baseline was performed. RESULTS: A total of 237 men were analyzed. Median age was 64 years (range, 44-86). Median followup was 24.8 months (range, 1-60). At baseline, 175 men (74%) reported erections firm enough for sexual activity and 148 (62%) were potent (erections firm enough for intercourse). Statistically significant changes in sexual function/bother were appreciated from baseline throughout the analysis period, although absolute changes were relatively small and did not meet criteria for clinical significance. At 24-months followup, 72% reported erections firm enough for sexual activity and 56% were potent. Of men with potency at baseline, 89% had erections firm enough for sexual activity and 76% remained potent 24 months after treatment. CONCLUSIONS: Peri-procedural tadalafil and prostate brachytherapy resulted in high rates of sexual potency preservation and no clinically significant effect on sexual quality of life.

Establishing high-quality prostate brachytherapy using a phantom simulator training program.

PURPOSE: To design and implement a unique training program that uses a phantom-based simulator to teach the process of prostate brachytherapy (PB) quality assurance and improve the quality of education. METHODS AND MATERIALS: Trainees in our simulator program were practicing radiation oncologists, radiation oncology residents, and fellows of the American Brachytherapy Society. The program emphasized 6 core areas of quality assurance: patient selection, simulation, treatment planning, implant technique, treatment evaluation, and outcome assessment. Using the Iodine 125 ((125)I) preoperative treatment planning technique, trainees implanted their ultrasound phantoms with dummy seeds (ie, seeds with no activity). Pre- and postimplant dosimetric parameters were compared and correlated using regression analysis. RESULTS: Thirty-one trainees successfully completed the simulator program during the period under study. The mean phantom prostate size, number of seeds used, and total activity were generally consistent between trainees. All trainees met the V100 >95% objective both before and after implantation. Regardless of the initial volume of the prostate phantom, trainees' ability to cover the target volume with at least 100% of the dose (V100) was not compromised (R=0.99 pre- and postimplant). However, the V150 had lower concordance (R=0.37) and may better reflect heterogeneity control of the implant process. CONCLUSIONS: Analysis of implants from this phantom-based simulator shows a high degree of consistency between trainees and uniformly high-quality implants with respect to parameters used in clinical practice. This training program provides a valuable educational opportunity that improves the quality of PB training and likely accelerates the learning curve inherent in PB. Prostate phantom implantation can be a valuable first step in the acquisition of the required skills to safely perform PB.

An MRI-based dose--reponse analysis of urinary sphincter dose and urinary morbidity after brachytherapy for prostate cancer in a phase II prospective trial.

PURPOSE: To compare dose-volume histogram variables for the internal and external urinary sphincters (IUS/EUS) with urinary quality of life after prostate brachytherapy. METHODS AND MATERIALS: Subjects were 42 consecutive men from a prospective study of brachytherapy as monotherapy with (125)I for intermediate-risk localized prostate cancer. No patient received hormonal therapy. Preplanning constraints included prostate V100 higher than 95%, V150 lower than 60%, and V200 lower than 20% and rectal R100 less than 1cm(3). Patients completed the Expanded Prostate Cancer Index Composite quality-of-life questionnaire before and at 1, 4, 8, and 12 months after implantation, and urinary domain scores were analyzed. All structures including the IUS and EUS were contoured on T2-weighted MRI at day 30, and doses received were calculated from identification of seeds on CT. Spearman's (nonparametric) rank correlation coefficient (ρ) was used for statistical analyses. RESULTS: Overall urinary morbidity was worst at 1 month after the implant. Urinary function declined when the IUS V285 was 0.4% (ρ=-0.32, p=0.04); bother worsened when the IUS V35 was 99% (ρ=-0.31, p=0.05) or the EUS V240 was 63% (ρ=-0.31, p=0.05); irritation increased when the IUS V35 was 95% (ρ=-0.37, p=0.02) and the EUS V265 was 24% (ρ=-0.32, p=0.04); and urgency worsened when the IUS V35 was 99.5% (ρ=-0.38, p=0.02). Incontinence did not correlate with EUS or IUS dose. CONCLUSIONS: Doses to the IUS and EUS on MRI/CT predicted worse urinary function, with greater bother, irritative symptoms, and urgency. Incorporating MRI-based dose-volume histogram analysis into the treatment planning process may reduce acute urinary morbidity after brachytherapy.

Magnetic resonance imaging-based treatment planning for prostate brachytherapy.

PURPOSE: Transrectal ultrasound (TRUS) is the standard imaging modality for planning prostate brachytherapy. However, magnetic resonance imaging (MRI) provides greater anatomic detail than TRUS. We compared treatment plans generated using TRUS, endorectal coil MRI (erMRI), and standard body array coil MRI (sMRI). METHODS AND MATERIALS: Treatment plans were used from patients treated with permanent, stranded-seed (125)I brachytherapy in a prospective trial. All men underwent pretreatment planning based on TRUS, and all underwent erMRI before treatment and sMRI 30 days after the implant. Treatments for 20 consecutive patients were replanned on sMRI and erMRI images by investigators blinded to TRUS-based plans. Prostate volume/dimensions, radioactivity-to-prostate-volume ratio, and dosimetric parameters were compared. RESULTS: Compared with TRUS, mean prostate volume measured by erMRI was smaller, medial-lateral diameter was larger, and anterior-posterior diameter was smaller, suggesting that the endorectal coil produced anatomic distortions. Craniocaudal prostate length was smaller on both types of MRI than on TRUS, suggesting that TRUS overestimates prostate length. Activity per volume was 7.5% lower for plans based on sMRI than on TRUS (0.901 vs. 0.974mCi/cm(3), p<0.001). sMRI plans had similar coverage of the planning target volume (PTV) (dose to 90% of the prostate [D(90)] 116.6% sMRI vs. 117.5% TRUS, p=0.526) and improved dose homogeneity (percentage of PTV receiving 150% of the prescription dose [V(150)] 47.4% sMRI vs. 53.8% TRUS, p=0.001 and percentage of PTV receiving 200% of the prescription dose [V(200)] 16.6% sMRI vs. 19.2% TRUS, p<0.001). CONCLUSIONS: Staging erMRI should not be routinely used for treatment planning because it produces anatomic distortion. sMRI may have treatment planning advantages over TRUS because of superior soft-tissue delineation of the prostate and adjacent normal tissue structures.

Improving prostate brachytherapy quality assurance with MRI-CT fusion-based sector analysis in a phase II prospective trial of men with intermediate-risk prostate cancer.

PURPOSE: We combined sector analysis with MRI-CT fusion to comprehensively assess postimplant dosimetry after prostate brachytherapy. METHODS AND MATERIALS: Subjects were 50 men with intermediate-risk prostate cancer treated with (125)I brachytherapy in a prospective phase II clinical trial. On Day 30 after the implantation, dosimetry was evaluated in the prostate base, midgland, and apex regions on fused MRI-CT scans and CT scans. Volumes of each sector receiving 100% of the prescribed dose (V100) and doses to 90% of each sector (D90) were also calculated on the ultrasonogram used for treatment planning and compared with values derived from CT and fused MRI-CT scans. RESULTS: Fused MRI-CT scans revealed lower-than-expected doses for the whole prostate (V100=91.3%, D90=152.9Gy) compared with CT scans (98.5% and 183.6Gy, p<0.0001) and lower doses to the prostate base (V100=79%, D90=130Gy) vs. CT (96% and 170Gy, p<0.0001). However, lower doses to the prostate base did not adversely affect biochemical outcomes in men with biopsy-proven disease at the base. At a median followup time of 42 months, the mean prostate-specific antigen level for all patients was 0.3ng/mL, and no patient had experienced biochemical or clinical progression or recurrence. CONCLUSIONS: MRI-CT fusion-based sector analysis was feasible and revealed significantly lower doses to the prostate base than doses estimated from CT alone, although this did not affect biochemical outcomes. MRI-CT fusion-based sector analysis may be useful for developing MRI-based dosimetric markers to predict disease outcomes and treatment-related morbidity.