Image-guided brachytherapy for prostate cancer

Prostate brachytherapy offers and effective treatment for organ-confined prostate carcinoma. It is rapidly delivered compared with external beam radiation therapy or surgery and well tolerated by patients. Volumetric imaging and image guidance play critical roles in patient selection, treatment planning, treatment delivery, and postimplant assessment. Costs, availability and ease of use often dictate the local and regional differences in imaging approach, whether ultrasound, CT, or MR. Future volumetric image developments may permit multimodality image fusion to integrate tumor-specific imaging such as MR spectroscopy or positron emission tomography/CT into real-time ultrasound, CT, or MR.     

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone

PurposeHigh-dose-rate (HDR) brachytherapy boost is a treatment of intermediate- to high-risk prostate cancer, but long-term clinical outcome data are sparse. We report long-term survival and toxicity data in a cohort of patients treated in a single institution.MethodsBetween 1998 and 2004, 654 patients with localized prostate cancer received either 3-dimensional conformal radiotherapy (median 46 Gy) with an HDR (median 18 Gy in three fractions) boost (“3-D conformal radiotherapy [3DCRT] + HDR”; 215 patients) or 3DCRT alone (“3DCRT”; median 70 Gy; 439 patients) with curative intent. Men with National Comprehensive Cancer Network intermediate risk were offered neoadjuvant androgen deprivation and with high risk were also offered adjuvant androgen deprivation. Data collection included patient-reported outcome measures.ResultsThe 3DCRT + HDR group was older (72.3 vs. 68.9 yrs), had higher presenting PSAs (iPSA) (15.66 and 12.57 ng/mL, respectively), higher proportion of Gleason scores >7 (15.3% vs. 12.4%), and higher proportions of extracapsular disease (29.3% vs. 25.5%). 3DCRT + HDR men had lower proportions of low-risk patients (3.3% vs. 19.4%) and higher proportions of high-risk patients (50.7% vs. 37.4%) than the 3DCRT group. The 5-, 10-, and 15-year overall survival was superior at 92%, 81%, and 67%, respectively, for the 3DCRT + HDR group, compared with 88%, 71%, and 53%, respectively, in the 3DCRT group (p < 0.001). The 5-, 10-, and 15-year cause specific survival also favored the HDR boost group with survival of 96%, 93%, and 87% (3DCRT + HDR) and 95% 88% and 79% (3DCRT), respectively (p < 0.037).ConclusionsHDR brachytherapy boost in conjunction with 3DCRT offered superior overall survival and cause-specific survival in our patient population.     

Salvage brachytherapy for recurrent prostate cancer

PurposeTo evaluate the role of salvage prostate brachytherapy for locally recurrent prostate cancer after external beam radiation alone.Methods and MaterialsSixty-nine consecutive patients treated with salvage brachytherapy after a local failure were analyzed. All patients were found to have pathologic proven recurrent prostate cancer at least 2 years after initial therapy and no regional or distant disease on imaging studies. Pd-103 was used with a prescribed pD₉₀ of 100 Gy. In total, 89.9% of patients received androgen suppression (AS) as part of their salvage therapy. Patients whose prostate-specific antigen >5.0 ng/mL while on AS were considered to have castration resistant prostate cancer (CRPC). Patients on AS >6 months before salvage brachytherapy were considered to have delayed therapy. Patients retreated within 5 years after their initial treatment were considered to have early failures.ResultsTotal median followup after salvage therapy was 5.0 years (0.6–13.7). From the date of salvage, 5-year biochemical control for low-risk patients was 85.6%, intermediate-risk patients 74.8%, and high-risk patients 66%. Five-year biochemical control was 73.8% for non-CRPC and 22% for CRPC cases (<0.001). Including and excluding CRPC cases, early treatment after failure vs. delayed treatment was significantly better (p < 0.05). Chronic adverse events were seen in few patients, with genitourinary Grade 3 toxicity of 8.7% and no genitourinary Grade 4 or gastrointestinal Grade 3 or higher toxicities.ConclusionsA subset of failures after definitive radiation is local in nature, and excellent control is possible with salvage brachytherapy.     

Efficacy of prophylactic single-dose therapy using fluoroquinolone for prostate brachytherapy

Purpose  

There is little definitive evidence to guide the use of prophylactic antibiotics for prostate brachytherapy. The purpose of this study is to evaluate the incidence of postimplant infections in patients who receive antimicrobial prophylaxis with pazufloxacin (PZFX).     

External radiotherapy and permanent prostate brachytherapy in patients with localized prostate cancer

We examined the difference in prostate-specific antigen (PSA)-freedom from recurrence (FFR) in patients with localized prostate cancer treated with permanent prostate brachytherapy (PPB) alone or external radiotherapy combined with PPB (RT-PPB). A total of 1476 patients with prostate cancer (T1/T2) were treated with PPB by following the American Brachytherapy Society criteria. Patient self-selection and preference allowed for an overlap of treatment methodologies and risk factors. Monotherapy consisted of 125I or 103Pd. RT-PPB consisted of RT followed by PPB. PSA-FFR was based on a published modification of the American Society for Therapeutic Radiology and Oncology definition. Cox regression analysis was performed to assess the role of Gleason sum, pretreatment PSA value, clinical stage, RT-PPB, the addition of hormones, and the minimum dose covering 90% of the prostate volume (D90 dose). Monotherapy was used for 1016 patients (79%), and RT-PPB was used for 281 patients (21%), with an overall 6-year PSA-FFR of 83.2% (median follow-up of 34.7 months; range, 6-91 months). Multivariate Cox regression analysis to predict PSA-FFR identified the following highly significant variables: pretreatment PSA value, Gleason sum, and the addition of hormones. When the D90% (D90 dose relative to the prescribed dose) was included as a variable, Cox regression identified only the following significant variables: D90%, pretreatment PSA, and Gleason sum. Cox regression failed to identify an improvement in PSA-FFR with RT-PPB or the addition of hormones. Although these conclusions question the role for RT-PPB, only a comparative trial will be able to answer this question definitively.     

Validation study of ultrasound-based high-dose-rate prostate brachytherapy planning compared with CT-based planning

PurposeThe use of transrectal ultrasound (TRUS) to both guide and plan high-dose-rate (HDR) brachytherapy (BT) for prostate is increasing. Studies using prostate phantoms have demonstrated the accuracy of ultrasound (US) needle tip reconstruction compared with CT imaging standard. We have assessed the in vivo accuracy of needle tip localization by TRUS using cone-beam CT (CBCT) as our reference standard.Methods and MaterialsNeedle positions from 37 implants have been analyzed. A median of 16 needles (range, 16–18) per implant were inserted, advanced to the prostate base, and their tips identified using live TRUS images and real-time planning BT software. Needle protrusion length from the template was recorded to allow for reverification before capturing images for planning. The needles remained locked in the template, which was fixed to the stepper, while a set of three-dimensional TRUS images was acquired for needle path reconstruction and HDR-BT treatment planning. Following treatment, CBCT images were acquired for subsequent needle reconstruction using a BT Treatment Planning System. The coordinates of each needle tip were recorded from the Treatment Planning System for CT and US and compared.ResultsA total of 574 needle tip positions have been compared between TRUS and CBCT. Of these, 59% agreed within 1 mm, 27% within 1–2 mm, and 11% agreed within 2–3 mm. The discrepancy between tip positions in the two modalities was greater than 3 mm for only 20 needles (3%).ConclusionsThe US needle tip identification in vivo is at least as accurate as CT identification, while providing all the advantages of a one-step procedure.     

Low-dose-rate brachytherapy for prostate cancer in renal transplant recipients

PURPOSEProstate cancer (PCa) is the most common malignancy among men and one of the most common neoplasms affecting renal transplant recipients (RTRs). The available treatments for localized PCa among the general population (GP), surgery and external beam radiotherapy, carry a risk of damage to the transplanted kidney, the ureters, and the bladder and therefore tend to be avoided by most groups. The objective of this study was to assess the efficacy and feasibility of low-dose-rate brachytherapy (LDR-BT) for PCa in RTRs.METHODS AND MATERIALSWe carried out a retrospective review on all RTRs diagnosed of PCa who had undergone LDR-BT at our institution between 2000 and 2015. Nine patients met these criteria, but 1 did not fulfill the followup. Hence, we analyzed 8 patients. We reviewed all clinical data for PCa and graft function in these patients and compared the results with the GP.ResultsMean baseline prostate-specific antigen was 6.8 ± 1.9 ng/mL. All PCa had a Gleason score of 6 and were classified as low risk according the Europe Association of Urology guidelines. Mean followup after seed implantation was 48 ± 12.8 months. All 8 patients remain free of prostate-specific antigen failure. Five-year progression-free survival, cancer-specific survival, and overall survival rates were 100%, 100%, and 62.5%. There was no specific toxicity associated with LDR-BT, and there were no acute adverse events affecting the graft.ConclusionsLDR-BT is a feasible and acceptable treatment for localized PCa in RTRs. Oncological outcomes are similar to the GP, and there is minimal toxicity to the renal graft.     

High-dose-rate interstitial brachytherapy in combination with androgen deprivation therapy for prostate cancer

Background and purpose

To evaluate the effectiveness of high-dose-rate interstitial brachytherapy (HDR-ISBT) as the only form of radiotherapy for high-risk prostate cancer patients.

Patients and methods

Between July 2003 and June 2008, we retrospectively evaluated the outcomes of 48 high-risk patients who had undergone HDR-ISBT at the National Hospital Organization Osaka National Hospital. Risk group classification was according to the criteria described in the National Comprehensive Cancer Network (NCCN) guidelines. Median follow-up was 73 months (range 12–109 months). Neoadjuvant androgen deprivation therapy (ADT) was administered to all 48 patients; 12 patients also received adjuvant ADT. Maximal androgen blockade was performed in 37 patients. Median total treatment duration was 8 months (range 3–45 months). The planned prescribed dose was 54 Gy in 9 fractions over 5 days for the first 13 patients and 49 Gy in 7 fractions over 4 days for 34 patients. Only one patient who was over 80 years old received 38 Gy in 4 fractions over 3 days. The clinical target volume (CTV) was calculated for the prostate gland and the medial side of the seminal vesicles. A 10-mm cranial margin was added to the CTV to create the planning target volume (PTV).

Results

The 5-year overall survival and biochemical control rates were 98 and 87?%, respectively. Grade 3 late genitourinary and gastrointestinal complications occurred in 2 patients (4?%) and 1 patient (2?%), respectively; grade 2 late genitourinary and gastrointestinal complications occurred in 5  patients (10?%) and 1 patient (2?%), respectively.

Conclusion

Even for high-risk patients, HDR-ISBT as the only form of radiotherapy combined with ADT achieved promising biochemical control results, with acceptable late genitourinary and gastrointestinal complication rates.     

Dosimetry of anal radiation in high-dose-rate brachytherapy for prostate cancer

PURPOSE: The objective of this study is to determine the radiation dose to the anus during brachytherapy using high-dose-rate Ir-192 sources. METHODS AND MATERIALS: Thermoluminescence dosimeters were used for measuring the dose to the distal part of the anus in 10 patients, and in a prostate phantom to measure the radiation dose during the transport of the radiation source. RESULTS: The measured dose to the anus in vivo was on average 0.85 Gy (range, 0.48-1.37 Gy) per treatment. The transport dose using 15 and 19 needles in the prostate phantom was 0.07 and 0.08 Gy, respectively. CONCLUSIONS: The dose delivered to the anus using high-dose-rate brachytherapy with Ir-192 sources is quite low. There is a contribution to the anal radiation dose during the transport of the Ir-192 source into the needles. However, in clinical practice when using 15-20 needles, the dose from transporting the Ir-192 source can be ignored.     

Favorable preservation of erectile function after prostate brachytherapy for localized prostate cancer

PurposeWe analyzed the rate of preserved potency after prostate brachytherapy (PB) with radioactive seeds and the impact of patient comorbidities on post-PB erectile dysfunction (ED).MethodsWe included 627 patients who were assessed for pre- and postimplant potency between 2005 and 2017. Assessment was based on the Common Terminology Criteria for Adverse Events Scale (CTCAEs). Logistic regression models were used to assess clinical predictors of preserved potency after PB defined as having sufficient erections for sexual activity with or without the need of oral pharmacologic assistance. Covariates included age, diabetes (DM), hypertension (HTN), dyslipidemia (DLP), coronary artery disease (CAD), International Prostate Symptom Score (IPSS), prostate volume, and Cancer of the Prostate Risk Assessments (CAPRA) score. Patients on androgen deprivation therapy or using five alpha reductase inhibitors were excluded from analyses.ResultsPost-PB potency was assessed at an average of 6 months (n = 627), 1 year (n = 538), 2 years (=440), 4 years (n = 272), and 5 years (n = 124). At 2 and 5 years, post-PB potency was preserved in 87% and 84% of patients, respectively. When adjusting for all available covariates, advanced age, pre-PB potency, and the presence of vascular comorbidities (HTN, DM, and DLP) were all predictors of potency at 2 years after PB (all p < 0.01). When performing a sensitivity analysis for vascular comorbidities, the presence of DM had the strongest impact on ED than either HTN or DLP (p < 0.01).ConclusionMore than 84% of patients had preserved potency 5 years after PB. Advanced age, pre-PB potency, and vascular comorbidities had a statistically significant impact on potency after PB.     

Long-term oncologic outcomes of low dose-rate brachytherapy compared to hypofractionated external beam radiotherapy for intermediate -risk prostate cancer

PURPOSETo compare the long-term oncologic outcomes of intermediate risk (IR) prostate cancer (PCa) patients treated with low dose-rate brachytherapy (LDR-BT) or moderate hypofractionated external beam radiotherapy (HF-EBRT).METHODS AND MATERIALSPatients diagnosed with IR PCa and treated with LDR-BT or HF-EBRT between January 2005 and December 2013 were included. Brachytherapy treatment involved a transperineal implant of iodine-125 to a dose of 145 Gy to the PTV, while HF-EBRT was delivered using intensity modulated radiotherapy with 60 Gy in 20 fractions. The Phoenix ‘‘nadir +2’’ threshold was used to define biochemical relapse (BR). The cumulative incidence function (CIF) of BR and metastases was reported for each group and compared using the Gray's test to account for the competing risk of death. The Kaplan-Meier (KM) method was used to estimate overall survival (OS) and prostate cancer specific survival (PCSS). Univariate (UVA) and multivariable (MVA) analysis of the CIF of BR and metastases were performed. A 2-tailed p-value ≤ 0.05 was considered statistically significant.RESULTSOverall, 122 and 124 patients were treated with LDR-BT and HF-EBRT respectively. Median follow-up was 95 months [interquartile range (IQR): 79–118] in the LDR-BT group and 96 months (IQR: 63–123) in the HF-EBRT group. BR was observed in 5 patients treated with LDR-BT and 34 treated with HF-EBRT. At 60 and 90 months, the CIF of BR was 0.9% and 3.5% in the LDR-BT group vs. 16.6% and 23.7% in the HF-EBRT (p < 0.001). The CIF of metastases at 90 and 108 months, was 0% and 1.6% vs. 3.4% and 9.1% in the LDR-BT and HF-EBRT groups (p = 0.003), respectively. At the last follow-up, 3 patients treated with HF-EBRT died from their cancer [PCSS of 97.5% at 8 years and none died in the LDR-BT group (p = 0.09). On UVA and MVA risk group and treatment modality were independently associated with CIF of BR. On UVA HF-EBRT and ISUP grade group 3 were associated with metastases.CONCLUSIONLDR-BT was associated with higher biochemical and metastases control in our cohort when compared to moderately HF-EBRT. In the absence of a randomized trial, LDR-BT when feasible should be offered to patients with a life expectancy of >8 years.     

Combined modality treatment with high-dose-rate brachytherapy boost for locally advanced prostate cancer

PURPOSE: This is a retrospective review of our experience using high-dose-rate (HDR) brachytherapy boost for prostate cancer. METHODS AND MATERIALS: During the study period, we recommended external beam radiotherapy (45 Gy) and HDR boost (18 Gy in three fractions) combined with hormonal therapy (HT) for 2 months before and during radiotherapy to patients with at least one of the following risk features: pretreatment prostate-specific antigen>10, Gleason score (GS)>or=7, and clinical T3 disease. Additional HT for 2 years after radiotherapy was recommended for patients with GS>7. To patients whose risk of positive nodes exceeded 15%, we recommended whole pelvic radiotherapy. We administered HDR via single implant, and all fractions were given within 24h. RESULTS: This report is based on our initial 64 patients treated with HDR boost. The median follow-up was 50 months (range 25-68 months). The 4-year estimates of overall and disease-free survival were 98% and 92%, respectively. One patient experienced late grade 4 gastrointestinal toxicity. CONCLUSIONS: HDR brachytherapy is an effective means of delivering conformal prostate radiotherapy, and may be used with whole pelvic radiotherapy and HT.     

Declining use of brachytherapy for the treatment of prostate cancer

PurposeTo analyze the recent trends in the utilization of external beam radiation therapy (EBRT) and brachytherapy (BT) for the treatment of prostate cancer.Methods and MaterialsUsing the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all patients diagnosed with localized prostate adenocarcinoma between 2004 and 2009 who were treated with radiation as local therapy. We evaluated the utilization of BT, EBRT, and combination BT + EBRT by the year of diagnosis and performed a multivariable analysis to determine the predictors of BT as treatment choice.ResultsBetween 2004 and 2009, EBRT monotherapy use increased from 55.8% to 62.0%, whereas all BT use correspondingly decreased from 44.2% to 38.0% (BT-only use decreased from 30.4% to 25.6%, whereas BT + EBRT use decreased from 13.8% to 12.3%). The decline of BT utilization differed by patient race, SEER registry, median county income, and National Comprehensive Cancer Network risk categorization (all p < 0.001), but not by patient age (p = 0.763) or marital status (p = 0.193). Multivariable analysis found that age, race, marital status, SEER registry, median county income, and National Comprehensive Cancer Network risk category were independent predictors of BT as treatment choice (all p < 0.001). Moreover, after controlling for all available patient and tumor characteristics, there was decreasing utilization of BT with increasing year of diagnosis (odds ratio for BT = 0.920, 95% confidence interval: 0.911–0.929, p < 0.001).ConclusionsOur analysis reveals decreasing utilization of BT for prostate cancer. This finding has significant implications in terms of national health care expenditure.     

高剂量率近距离放射治疗前列腺癌

高剂量率近距离放射治疗是根治前列腺癌的重要治疗手段之一，是近年来前列腺癌治疗领域的研究热点。着重介绍了高剂量率近距离放射治疗前列腺癌的原理，目前所采用的治疗技术，临床应用研究及其未来发展方向。