Use of individual fraction size data from 3756 patients to directly determine the alpha/beta ratio of prostate cancer

PURPOSE: To examine the effect of fraction size and total dose of radiation on recurrence of localized prostate cancer. METHODS AND MATERIALS: A total of 3756 patients treated with radiation monotherapy at three institutions were analyzed, including 185 high-dose-rate brachytherapy (HDRB) boost patients. The 5th to 95th centiles of external beam radiotherapy (EBRT) fraction sizes and doses were 1.8 to 2.86 Gy, and 57.4 to 77.4 Gy, respectively, and HDRB fractional doses were between 5.5 and 12 Gy, totaling 147 unique fractionation schedules. Failure was defined by one biochemical (nadir + 2 ng/ml) and two advanced disease endpoints. The alpha/beta ratios were estimated via a proportional hazards model stratified by risk severity and institution. RESULTS: The alpha/beta ratio using biochemical recurrence was 3.7 Gy (95% confidence interval [95% CI], 1.1, infinity Gy) for EBRT-only cases and 2.6 Gy (95% CI, 0.9, 4.8 Gy) after the addition of HDRB data. This estimate was highly dependent on an HDRB homogeneity correction factor (120% HDRB dose increase; alpha/beta ratio 4.5 Gy, 95% CI 1.6, 8.7 Gy). A 5-Gy increase in total dose reduced the hazard of failure by 16% (95% CI 11, 21%, p < 0.0001), and had more impact as follow-up matured (p < 0.0003). The clinically advanced endpoints concurred with the biochemical failure results, albeit with less precision. CONCLUSIONS: This study supports the concept that the alpha/beta ratio of prostate cancer is low, although considerable uncertainty remains in the estimated value. Outcome data from EBRT studies using substantially higher doses per fraction are needed to show increased precision in these estimates.     

Adjuvant high dose rate brachytherapy (Ir-192) in the management of keloids which have recurred after surgical excision and external radiation.

We describe our experience with adjuvant high dose rate brachytherapy (Ir-192) (HDRB) in patients, who failed surgery and post-operative external radiation therapy. The salvage treatment consisted of excision of the keloid and wound closure followed by HDRB (15 Gy in three fractions given on three consecutive business days beginning the day of surgery). At the time of last follow up, 88% (15/17) of the keloids were without any evidence of recurrence.     

Radiothérapie robotisée des cancers de prostate par CyberKnife™

After 3D conformal radiation therapy without and with modulated intensity, image-guided radiation therapy represents a new technological step. Should prostate cancer treatment using radiotherapy with the CyberKnife™ robotic system be considered as a new treatment and then investigated through classical clinical research procedure rather than a technical improvement of an already validated treatment? After a general presentation of the CyberKnife™, the authors focused on prostate cancer treatment assuming that, according to dosimetric and biological considerations, the treatment by robotic system appears comparable to high dose rate brachytherapy. For prostate cancer treatment are discussed: biological rational for hypofractionated treatment, high dose rate brachytherapy boost and interest of dose escalation. A comparison is presented between CyberKnife™ and other validated treatment for prostate cancer (radical prostatectomy, 3D conformal radiation therapy and low and high dose rate brachytherapy). In summary, CyberKnife™ treatment could be considered as a technical improvement of an already validated treatment in order to deliver a prostate boost after pelvic or peri-prostatic area irradiation. However, the clinical, biological and economical results must be precisely analyzed and could be assessed in the frame of a National Observatory based on shared therapeutic program.     

High dose rate brachytherapy for prostate cancer: Standard of care and future direction

High dose rate brachytherapy is a highly conformal method of radiation dose escalation for prostate cancer and one of several treatment options for men with localised disease. The large doses per fraction exploit the low alpha/beta ratio of prostate cancer cells so that biological radiation dose delivered is substantially greater than that achieved with conventional external beam delivery. This review article presents contemporary data on the rationale for high dose rate brachytherapy including treatment technique and future directions.     

High dose rate brachytherapy in the treatment of prostate cancer.

Because the HDR brachytherapy treatments are delivered within minutes and on an outpatient basis, HDR brachytherapy is very well tolerated by patients and offers complete radiation safety. Published studies2, 11, 12, 13, 16, 17, 18, 22, 24, 25 have shown high local clinical and biochemical control rates. Chronic complications have been acceptably low. Very low rates of urinary incontinence and high sexual potency rates have been reported. Gastrointestinal morbidity has been minimal. The development of Ir-192 HDR afterloading brachytherapy and refinements in the dosimetry have ushered in a new era in prostate brachytherapy. The control of the radiation dose and the ability to shape the radiation treatment envelope using a stepping source have allowed a giant step forward in radiation oncology technology. It is now possible to deliver tumoricidal doses of radiation conformally to the prostate while minimizing the dose to the bladder, urethra, and rectum. At present, HDR afterloaded brachytherapy is the optimal whole-organ and tumor-specific conformal radiation therapy for prostate cancer.     

Present and future in brachytherapy--from the discovery of radium to the 21st century]

Brachytherapy can deliver high doses of radiation to a tumor with only low doses to the normal tissue. Brachytherapy can be classified as intracavitary, intraluminar and interstitial radiotherapy. It can be also divided into three groups according to dose rate: low (LDR), medium (MDR) and high (HDR) dose rates. In recent years, HDR remotely controlled afterloading systems are widespread in Japan. HDR brachytherapy has solved the problem of radiation exposure for medical staff, and patients need not be isolated in highly sealed rooms. Local control rates of T1 and T2 tongue cancer treated with LDR interstitial radiation using 226Ra and 192Ir were 80% and 67%. A phase III trial of HDR versus LDR interstitial brachytherapy for early tongue cancer revealed the same local control rates between the two groups. For uterine cervix cancer, the cause-specific survival rates of patients treated with HDR intracavitary brachytherapy were almost the same as those treated with LDR. HDR brachytherapy can be applied against recurrent tumors. Almost half of recurrent tumors can be controlled with HDR treatment. Brachytherapy is widely used for prostate cancer in the USA. LDR brachytherapy using 125I seeds is used for prostate cancer. In Japan, 125I seeds can not be used because of the regulation of radioisotopes, so we treat prostate cancer patients with HDR brachytherapy. The two-year biochemical NED rate is 83%. Brachytherapy has a long history of nearly 100 years. In recent years, the development of an HDR remotely controlled afterloading system and treatment planning system allows us to make a precise treatment plan and a uniform dose distribution. In the next century, HDR-brachytherapy will continue to play an important role in the field of radiotherapy.     

High-dose-rate Rotte "Y" applicator brachytherapy for definitive treatment of medically inoperable endometrial cancer: 10-year results

PURPOSE: To assess the intermediate clinical outcomes of medically inoperable patients with endometrial cancer treated with definitive Rotte "Y" applicator high-dose-rate brachytherapy (HDRB) over a 10-year period. METHODS AND MATERIALS: Forty-nine inoperable patients were treated with HDRB from 1997 to 2007. Forty three (84%) were markedly obese (body mass index >35 kg/m(2)). Thirty-one patients (63.3%) underwent two-dimensional treatment planning, whereas 18 patients (36.7%) underwent three-dimensional treatment planning. Thirty five of the patients (71.4%) were first treated with external beam radiotherapy (EBRT). For patients receiving EBRT in addition to HDRB, the median Y-applicator dose was 20 Gy in 5 fractions; for patients receiving HDRB alone it was 35 Gy in 5 fractions. All patients received two Y-applicator treatments per day. RESULTS: Median follow-up time for all patients was 33 months. Acute HDRB toxicities were limited to Grade 1 and 2 occurring in 5 patients. One patient had a myocardial infarction. Four patients had late Grade 2 or 3 toxicity. Three patients had local recurrence (median time to recurrence, 16 months). The 3- and 5-year actuarial cause-specific survival rates were 93% and 87%, respectively; the overall survival rate was 83% and 42%, respectively, at 3 and 5 years. CONCLUSIONS: Twice-daily HDRB using a Y-applicator is a well-tolerated and efficacious regimen for the definitive treatment of medically inoperable patients with early-stage endometrial cancer. The recent incorporation of three-dimensional treatment planning has the potential to further decrease treatment morbidities.     

Combination external beam radiation and brachytherapy boost with androgen deprivation for treatment of intermediate-risk prostate cancer: long-term results of CALGB 99809

BACKGROUND:

Combined transperineal prostate brachytherapy and external beam radiation therapy (EBRT) is widely used for treatment of prostate cancer. Long‐term efficacy and toxicity results of a multicenter phase 2 trial assessing combination of EBRT and transperineal prostate brachytherapy boost with androgen deprivation therapy (ADT) for intermediate‐risk prostate cancer are presented.

METHODS:

Intermediate‐risk patients per Memorial Sloan‐Kettering Cancer Center/National Comprehensive Cancer Network criteria received 6 months of ADT, and 45 grays (Gy) EBRT to the prostate and seminal vesicles, followed by transperineal prostate brachytherapy with I¹²⁵ (100 Gy) or Pd¹⁰³ (90 Gy). Toxicity was graded using the National Cancer Institute Common Toxicity Criteria version 2 and Radiation Therapy Oncology Group late radiation morbidity scoring systems. Disease‐free survival (DFS) was defined as time from enrollment to progression (biochemical, local, distant, or prostate cancer death). In addition to the protocol definition of biochemical failure (3 consecutive prostate‐specific antigen rises >1.0 ng/mL after 18 months from treatment start), the 1997 American Society for Therapeutic Radiology and Oncology (ASTRO) consensus and Phoenix definitions were also assessed in defining DFS. The Kaplan‐Meier method was used to estimate DFS and overall survival.

RESULTS:

Sixty‐one of 63 enrolled patients were eligible. Median follow‐up was 73 months. Late grade 2 and 3 toxicity, excluding sexual dysfunction, occurred in 20% and 3% of patients. Six‐year DFS applying the protocol definition, 1997 ASTRO consensus, and Phoenix definitions was 87.1%, 75.1%, and 84.9%. Six deaths occurred; only 1 was attributed to prostate cancer. Six‐year overall survival was 96.1%.

CONCLUSIONS:

In a cooperative setting, combination of EBRT and transperineal prostate brachytherapy boost plus ADT resulted in excellent DFS with acceptable late toxicity for patients with intermediate‐risk prostate cancer. Cancer 2011;. © 2011 American Cancer Society.     

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

PURPOSE: The etiology of erectile dysfunction after definitive local therapy for carcinoma of the prostate gland represents a multifactorial phenomenon including neurogenic compromise, venous insufficiency, local trauma, and psychogenic causes. It has been suggested that impotence after prostate brachytherapy is a consequence of excessive radiation dose to the neurovascular bundles (NVB). Herein we evaluate the potential relationship between radiation dose to the NVB and the development of erectile dysfunction following prostate brachytherapy. METHODS AND MATERIALS: The radiation dose to the NVB was evaluated for 33 patients who developed erectile dysfunction (ED) following brachytherapy plus 21 additional patients who were potent before and subsequent to brachytherapy. Of the 54 patient study group, the median follow up was 37 months, and 25 patients were managed with (125)I as a monotherapeutic approach and 29 received (103)Pd as a boost following 45 Gy of external beam radiation therapy. Radiographic localization of the NVB was performed via a two-dimensional geometric model that placed 3-NVB calculation points on the left and right posterolateral side of each 5-mm CT slice. Parameters evaluated included dose-surface histograms, dose parameters via point doses on each slice, the magnitude of the dose in relationship to the distance from the base, and the relationship between NVB radiation dose in patients with and without ED, patient response to sildenafil and case sequence number. RESULTS: In terms of percent prescribed minimum peripheral dose (% mPD), there was no significant difference in mean neurovascular bundle dose between potent and impotent patients, between the isotopes ((125)I or (103)Pd), mono- or boost therapy, or side of the prostate for which the overall average was 217% +/- 55% of mPD. There was also no significant dosimetric difference in terms of response to sildenafil based on a multivariate analysis which included % mPD and various dose thresholds and side of the gland. The dose distribution over the length of the prostate rose smoothly from the base and apex to peak at midgland in (125)I implants while (103)Pd implants had a relatively constant dose over the length of the prostate. Considering the calculation grid as forming a 6-mm wide ribbon along each side of the prostate, the average patient had 70 mm(2) area receiving at least 300% of mPD. CONCLUSION: In this study, no relationship between radiation dose to the NVB and the development of post brachytherapy erectile dysfunction was discernible. Such a difference may become evident with additional follow-up. If long-term brachytherapy-induced erectile dysfunction is related to the radiation dose to the NVB, the ultimate preservation of potency following prostate brachytherapy may be markedly inferior to what has been reported. Nevertheless, the majority of this patient population responded favorably to sildenafil.     

Brachytherapy boost techniques for locally advanced prostate cancer

Brachytherapy boosts in combination with external-beam radiation therapy allow a highly conformal dose of radiation to be delivered to the prostate in a safe, efficient manner. Several types of brachytherapy boost techniques are used currently. Techniques based on transrectal ultrasound (TRUS) guidance clearly provide the most accurate method of radioactive source placement with reduced toxicity. Temporary implants employing remote afterloading systems with high-dose-rate (HDR) brachytherapy offer the added advantage of further optimizing dose distribution after needle placement. Novel brachytherapy programs using intraoperative real-time dosimetric analyses provide additional options for performing truly conformal dose escalation. Results with these newer boost techniques appear to be as good as or better than other forms of therapy in comparably staged patients. Until standardized methods of reporting treatment data are uniformly applied and longer follow-up is obtained with other treatment modalities, brachytherapy boosts combined with external-beam radiation should be considered an acceptable treatment option for patients with locally advanced prostate cancer. The challenge for the future will be to determine which treatment approach is optimal given certain critical pretreatment prognostic factors. In addition, the role of adjuvant androgen deprivation in controlling this malignancy will be critical and awaits the results of several recently initiated or completed randomized trials.     

Long-term results of high-dose-rate brachytherapy in the primary treatment of medically inoperable stage I-II endometrial carcinoma

PURPOSE: Total-abdominal hysterectomy and bilateral salpingo-oophorectomy (TAHBSO) is the gold-standard therapy for patients with endometrial carcinoma. However, patients with high operative risks are usually treated with radiation therapy (RT) alone. The goal of this study was to update our experience of high-dose-rate brachytherapy (HDRB), with or without external-beam irradiation (EBRT), for such patients. METHODS AND MATERIALS: Between 1984 and 2003, 38 patients with Stage I and Stage II adenocarcinoma of the endometrium considered high operative risk received RT as the primary treatment. The median age was 74.1 years. Before 1996, the local extent of the disease was assessed by an examination under anesthesia (EUA) and by EUA and magnetic resonance imaging (MRI) thereafter. Eight patients (21%) were treated with combined HDRB and EBRT, and 30 patients (79%) were treated with with HDRB alone. The median HDRB dose was 23.9 Gy, typically delivered in 3 fractions in a weekly schedule. The median EBRT dose was 42 Gy. RESULTS: At a median follow-up of 57.5 months for patients at risk, 11 patients (29%) have failed: 6 patients (16%) locally, 4 patients (10.5%) distantly, and 1 patient (3%) locally and distantly. Local failure was established by biopsy, and 4 patients were salvaged by TAHBSO. Higher stage and higher grade were both associated with increased failure rate. The 15-year disease-specific survival (DSS) was 78% for all stages, 90% for Stage I, and 42% for Stage II (p < 0.0001). The 15-year DSS was 91% for Grade I and 67% for Grade II and III combined (p = 0.0254). Patients with Stage I disease established by MRI (11 patients) and who received a total HDRB dose of 30 Gy had a DSS rate of 100% at 10 years. Four patients experienced late toxicities: 1 Grade II and 3 Grade III or IV. CONCLUSION: Medically inoperable Stage I endometrial carcinoma may be safely and effectively treated with HDRB as the primary therapy. In selected Stage I patients, our results are equivalent to that of surgery. We believe that the alternative option of HDRB as the primary therapy for selected Stage I endometrial carcinoma, even in patients with low operative risks, needs further evaluation.     

The use of magnetic resonance imaging for image-guided brachytherapy

Progress has been made in the delivery of brachytherapy, from low-dose rate (LDR) to high-dose rate (HDR) treatments, allowing for dose optimisation, conformal treatments, improved radiation protection, and improved accuracy and efficiency. Image-guided brachytherapy, incorporating spatial and temporal changes, is now possible with advanced imaging and treatment technology. This report reviews the evidence for the benefits of image-guided brachytherapy using magnetic resonance imaging (MRI), mainly for cervix and prostate cancer, but also possibilities for other tumour sites. It also emphasises the need for a dedicated MRI unit for brachytherapy.     

高剂量率近距离治疗前列腺癌进展北大核心CSCD

近距离放射治疗在局限期前列腺癌治疗中发挥重要作用。高剂量率近距离放疗经过几十年发展,作为单纯治疗或结合外照射增量治疗,与其他治疗相比,具有众多优势:精确提升靶区剂量,降低危及器官受量等。前列腺癌α/β值较小,单次高剂量HDR会诱导肿瘤基因的转录,提高放射敏感性。本文从HDR近距离放疗发展历史、患者选择、技术应用、疗效及不良反应等方面展开综述。     

The emerging role of high-dose-rate brachytherapy for prostate cancer

By placing radioactive sources directly into the cancer, brachytherapy allows delivery of a highly conformal radiation dose to the prostate. Permanent seed brachytherapy is most commonly used for low-risk cancer, whereas high-dose-rate (HDR) brachytherapy is combined with external-beam radiotherapy to treat higher risk disease. The high rate of dose delivery and the large fraction size may be a radiobiological advantage for tumours with high sensitivity to radiation fraction size. The ability to optimise dose delivery allows for exquisite shaping of dose around the prostate and sparing of normal tissues. HDR brachytherapy is most commonly delivered in two or more fractions of 810 Gy combined with 40-50 Gy external beam. Published studies are almost entirely limited to single-institution case series. Most of the patients treated have relatively unfavourable localised disease, with a reported disease-free survival of 68-93%, and a local control rate of over 90%. Treatment is well tolerated, with urethral stricture the most common late effect (risk around 8%). Early results using HDR monotherapy in low-risk disease seem promising. Patients most likely to benefit from a combined HDR/external-beam approach have bulky local disease (stage T2b-T3) or intermediate to high-grade cancers. Prospective multicentre studies of HDR brachytherapy have begun in this patient group in Canada and the USA, which hopefully will allow future comparisons with high-dose conformal external-beam techniques.     

Toxicity and health-related quality of life during and after high dose rate brachytherapy followed by external beam radiotherapy for prostate cancer.

BACKGROUND: The optimal protocol for combining high dose rate brachytherapy and external beam irradiation as treatment for localized prostate cancer is unknown. Toxicity rates and clinical and biochemical outcomes should be evaluated to validate the current treatment protocol. METHODS: Fifty-eight patients were treated for prostate cancer with high dose rate brachytherapy followed by 30 Gy of external beam radiation therapy. Toxicity during treatment and for 12-18 months thereafter, and treatment-related morbidity, were evaluated. Physician-assessed treatment-related toxicity was graded at the time of occurrence using the Radiation Therapy Oncology Group morbidity criteria. Four separate self-administered questionnaires were used to collect longitudinally demographic data and general and prostate disease-related measures of quality of life. RESULTS: Various degrees of rectal bleeding due to radiation proctitis were experienced by 13 patients (22%) at a median time of 11 months. Two of these patients needed hospitalization to undergo laser coagulation of the rectal mucosa. Study patients had statistically significant decreases in five SF-36 domains during the first month of treatment. All measures recovered by 12 months. Sexual function was not affected by irradiation. Lower urinary tract symptoms assessed by IPSS/QOL scores worsened significantly during the first month of treatment but later recovered to baseline levels. Physician-assessed RTOG scores failed to detect these changes. CONCLUSIONS: Morbidity associated with combined radiation therapy was greatest during the first month of treatment and affected quality of life significantly. Most measures recovered to baseline levels by 12 months following radiation therapy. Although the current protocol appears acceptable, measures should be taken to decrease treatment-related morbidity further.     

Place of modern imaging in brachytherapy planning

Imaging has probably been the most important driving force for the development of brachytherapy treatments the last 20 years. Due to implementation of three-dimensional imaging, brachytherapy is nowadays a highly accurate and reliable treatment option for many cancer patients. To be able to optimize the dose distribution in brachytherapy the anatomy and the applicator(s) or sources should be correctly localised in the images. For computed tomography (CT) the later criteria is easily fulfilled for most brachytherapy sites. However, for many sites, like cervix and prostate, CT is not optimal for delineation since soft tissue is not adequately visualized and the tumor is not well discriminated. For cervical cancer treatment planning based on magnetic resonance imaging (MRI) is recommended. Some centres also use MRI for postimplant dosimetry of permanent prostate seed implant and high dose rate prostate brachytherapy. Moreover, in so called focal brachytherapy where only a part of the prostate is treated, multiparametric MRI is an excellent tool that can assist in defining the target volume. Applicator or source localization is challenging using MRI, but tolls exist to assist this process. Also, geometrical distortions should be corrected or accounted for. Transrectal ultrasound is considered to be the gold standard for high dose rate prostate brachytherapy and transrectal ultrasound -based brachytherapy procedure offers a method for interactive treatment planning. Reconstruction of the needles is sometimes challenging, especially to identify the needle tip. The accuracy of the reconstruction could be improved by measuring the residuals needle length and by using a bi-planar transducer. The last decade several groups worldwide have explored the use of transrectal and transabdominal ultrasound for cervical cancer brachytherapy. Since ultrasonography is widely available, offers fast image acquisition and is a rather inexpensive modality such development is interesting. However, more work is needed to establish this as an adequate alternative for all phases of the treatment planning process. Studies using positron emission tomography imaging in combination with brachytherapy treatment planning are limited. However, development of new tracers may offer new treatment approaches for brachytherapy in the future. Combination of several image modalities will be the optimal solution in many situations, either during the same session or for different fractions. When several image modalities are combined so called image registration procedures are used and it is important to understand the principles and limitations of such procedures.     

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.     

Urethral stricture following high dose rate brachytherapy for prostate cancer

Purpose

To evaluate the incidence, timing, nature and outcome of urethral strictures following high dose rate brachytherapy (HDRB) for prostate carcinoma.

Methods and materials

Data from 474 patients with clinically localised prostate cancer treated with HDRB were analysed. Ninety percent received HDRB as a boost to external beam radiotherapy (HDRBB) and the remainder as monotherapy (HDRBM). Urethral strictures were graded according to the Common Terminology Criteria for Adverse Events v3.0.

Results

At a median follow-up of 41 months, 38 patients (8%) were diagnosed with a urethral stricture (6-year actuarial risk 12%). Stricture location was bulbo-membranous (BM) urethra in 92.1%. The overall actuarial rate of grade 2 or more BM urethral stricture was estimated at 10.8% (95% CI 7.0-14.9%), with a median time to diagnosis of 22 months (range 10-68 months). All strictures were initially managed with either dilatation (n = 15) or optical urethrotomy (n = 20). Second line therapy was required in 17 cases (49%), third line in three cases (9%) and 1 patient open urethroplasty (grade 3 toxicity). Predictive factors on multivariate analysis were prior trans-urethral resection of prostate (hazard ratio (HR) 2.81, 95% CI 1.15-6.85, p = 0.023); hypertension (HR 2.83, 95% CI 1.37-5.85, p = 0.005); and dose per fraction used in HDR (HR for 1 Gy increase per fraction 1.33, 95% CI 1.08-1.64, p = 0.008).

Conclusions

BM urethral strictures are the most common late grade 2 or more urinary toxicity following HDR brachytherapy for prostate cancer. Most are manageable with minimally invasive procedures. Both clinical and dosimetric factors appear to influence the risk of stricture formation.     

Innovations thérapeutiques en radiothérapie du cancer de la prostate localisé

Intensity-modulated radiation therapy, image-guided radiation therapy with fiducial markers and prostate brachytherapy allow the delivery of dose escalation for localized prostate cancer with very low rates of long-term toxicity and sequelae. Nowadays, modern radiotherapy techniques make it possible to shorten treatment time with hypofractionation, to better protect surrounding healthy tissues and to escalate the dose even further. Advances in radiotherapy are closely linked to advances in magnetic resonance imaging (MRI) and/or PET imaging. Functional imaging makes it possible to deliver personalised pelvic nodal radiotherapy, targeting the nodal areas at higher risk of microscopic involvement. In patients with an index lesion at baseline or at failure, MR-based focal therapy or focal dose escalation with brachytherapy or stereotactic body radiation therapy is also currently investigated. MR-based adaptive radiotherapy, which makes it possible to track prostate shifts during radiation delivery, is another step forward in the integration of MR imaging in radiation delivery.