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.     

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.     

High dose rate brachytherapy boost treatment in radical radiotherapy for prostate cancer.

The natural history of prostate cancer is for early invasion of the prostatic capsule and seminal vesicles. This will be present in the majority of patients presenting with a prostate specific antigen (PSA) >10 or Gleason score >7. In these patients a combination of external beam treatment to provide a regional dose of radiation followed by a high dose rate afterloading brachytherapy boost to enable conformal dose escalation within the prostate gland presents an attractive option in local treatment. Accurate placement of catheters is now possible using transrectal ultrasound to provide high quality implants. A number of centres have now developed this technique as a routine clinical tool. There remains variation in the optimal dose fractionation with a range of BED(10) values from 100 to 77 and BED(3) values from 246.6 to 122.5. This does not, however, take into account geometric variations in dose distribution exploiting the physical advantage of BT in achieving a rapid dose fall off close to critical structures such as the rectum. Early results show PSA response levels of around 90% with grade III toxicity in 5-9% of patients. Critical evaluation of this technique in prospective, randomized trials is required.     

前列腺癌放射治疗

放射治疗目前不仅用于早期局限性前列腺癌的根治性治疗，亦逐渐应用于局部晚期前列腺癌的治疗、手术后的辅助性治疗以及与内分泌联合治疗。除外照射放射治疗外，组织问插植放射治疗，3-D适形放射治疗等技术也愈来愈多地应用于前列腺癌的治疗。该文重点讨论各种放疗技术在前列腺癌治疗中的适应证、疗效与副反应。     

Endobronchial brachytherapy: an effective option for palliation of malignant bronchial obstruction

Symptoms resulting from tumors extending to the endobronchial wall are common in patients with lung cancer and significantly impact quality of life. A number of treatment options are available for palliation, including endobronchial brachytherapy, stent placement, laser photoresection, external-beam radiation therapy, and photodynamic therapy. This review will focus on the methodology and role of endobronchial brachytherapy while discussing benefits of other treatment options as additions or alternatives to brachytherapy.     

Update on radiation therapy in prostate cancer

Higher doses of radiation result in improved clinical control of prostate cancer,and the recent advances in prostate cancer radiotherapy are designed to escalate dose while minimizing toxicity. To achieve this goal, tighter treatment margins are needed, which require more accurate delineation of the prostate target and normal tissue at the time of treatment planning and before actual daily treatments. Modem radiation therapy techniques can deposit conformal dose virtually anywhere in the body; however, this precise therapy is of no value if it is not accurately hitting the target. Whether dose escalation is achieved by external beam techniques (eg, IMRT, protons) or brachytherapy, these ba-sic planning and delivery considerations are essentially the same. Future directions in prostate radiation therapy will use even higher radiation doses,alternative fractionation patterns, intraprostatic targets (eg, prostate tumor seen on MRI), and improved patient selection regarding which patients will benefit the most from these advanced techniques.     

Permanent prostate brachytherapy: lessons learned, lessons to learn

Current techniques for permanent prostate brachytherapy are associated with excellent biochemical control in patients with localized prostate cancer. Data now available confirm 5- to 10-year results with this treatment modality that are comparable to those with external-beam irradiation or radical prostatectomy. Nonetheless, treatment protocols and techniques for prostate brachytherapy vary from center to center. Controversy exists regarding the selection of patients for brachytherapy alone or in combination with external-beam irradiation. The role of neoadjuvant androgen deprivation also remains undefined in patients with localized prostate cancer. Matched-pair analysis studies performed at Memorial Sloan-Kettering Cancer Center have examined the role of isotope selection, the addition of external-beam irradiation, and the use of neoadjuvant androgen deprivation. These studies provide insights into the use of permanent brachytherapy in patients with localized prostate cancer. In addition, postimplant dosimetry needs to be a requirement for centers performing seed implants. Data now appear to support specific computed tomography-based criteria to evaluate implant quality and delivered dose to the prostate. Unfortunately, prostate edema and poor imaging techniques limit the evaluation of implant dosimetry. Treatment planning techniques that utilize new imaging modalities, coupled with computerized treatment planning, may help improve the implant procedure and dosimetry.     

Endobronchial Brachytherapy: An Effective Option for Palliation of Malignant Bronchial Obstruction

Symptoms resulting from tumors extending to the endobronchial wall are common in patients with lung cancer and significantly impact quality of life. A number of treatment options are available for palliation, including endobronchial brachytherapy, stent placement, laser photoresection, external-beam radiation therapy, and photodynamic therapy. This review will focus on the methodology and role of endobronchial brachytherapy while discussing benefits of other treatment options as additions or alternatives to brachytherapy.     

A second transient prostate-specific antigen elevation after external-beam radiation therapy and fractionated magnetic resonance imaging-guided high-dose rate brachytherapy boost

A 63-year-old man with a T1c adenocarcinoma of the prostate, Gleason score of 7 (4+3), and a pretreatment prostate-specific antigen (PSA) level of 9.5 ng/mL was treated with external-beam radiation therapy (45 Gy) and 2 magnetic resonance imaging-guided high-dose rate brachytherapy boosts (10 Gy each.) The patient also received neoadjuvant, concurrent, and adjuvant hormonal treatment with leuprolide for 7 months total. Without any further intervention the patient had 2 separate and prolonged PSA increases and decreases 12-35 months after therapy. His PSA nadir was <0.2 ng/mL and rose slowly over several months to 4.2 ng/mL, resolved, and then rose 2.3 ng/mL before again slowly resolving. After prostate irradiation, many patients experience a transient rise in serum PSA levels and a subsequent decline without any treatment. This is known as a PSA "bounce" or "bump." Some patients experience a second transient rise in PSA levels after irradiation. To our knowledge, this case report is the first documentation of a second PSA bump in a patient treated with external-beam radiation therapy and high-dose rate boost therapy and provides context to address concerns and therapeutic decisions confronting physicians and patients.     

Technology Insight: Combined external-beam radiation therapy and brachytherapy in the management of prostate cancer

External-beam radiation therapy (EBRT) combined with brachytherapy is an attractive treatment option for selected patients with clinically localized prostate cancer. This therapeutic strategy offers dosimetric coverage if local-regional microscopic disease is present and provides a highly conformal boost of radiation to the prostate and immediate surrounding tissues. Either low-dose-rate (LDR) permanent brachytherapy or high-dose-rate (HDR) temporary brachytherapy can be combined with EBRT; such combined-modality therapy (CMT) is typically used to treat patients with intermediate-risk to high-risk, clinically localized disease. Controversy persists with regard to indications for CMT, choice of LDR or HDR boost, isotope selection for LDR, and integration of EBRT and brachytherapy. Initial findings from prospective, multicenter trials of CMT support the feasibility of this strategy. Updated results from these trials as well as those of ongoing and new phase III trials should help to define the role of CMT in the management of prostate cancer. In the meantime, long-term expectations for outcomes of CMT are based largely on the experience of single institutions, which demonstrate that CMT with EBRT and either LDR or HDR brachytherapy can provide freedom from disease recurrence with acceptable toxicity.     

Radiation Therapy Techniques and Dose Selection in the Treatment of Prostate Cancer

A dose response for local control of cancer of the prostate is shown, and normal tissue irradiated volume and complications are diminished with conformal radiation therapy techniques in prostate cancer. Refinements in techniques and technology, as well as phase II trials are underway. Should these studies prove dose escalation to be safe, a phase III trial comparing standard techniques and dose with conformal high dose radiotherapy is warranted for patients with adenocarcinoma of the prostate. If a phase III study is positive, then it will confirm that local control of prostate cancer can be improved with conformal therapy techniques without increasing the morbidity of treatment. However, if this is proven to be true only for institutions with highly specialized equipment, then this finding will have very little impact on the total treatment of prostate cancer or consequences of this disease. A truly successful trial will produce results that can be duplicated in modern radiation therapy centers that have conscientiously maintained current, but not necessarily esoteric technology; it is in the best interests of our patients and our colleagues to develop treatment technologies that can be implemented at all institutional strata.     

Brachytherapy for prostate cancer: Present and future

Based on recent, important publications on the impact of brachytherapy in the management of prostate cancer, we analysed already validated indications and the “under investigations” use of brachytherapy. Published studies (MEDLINE), randomized trials and recommendations were reviewed, as well as Delphi consensus when available. While low-dose rate brachytherapy remains a standard of care for low-risk eligible patients, three randomized trials are now available to consider that combination of external beam radiation therapy with brachytherapy boost (low- or high-dose rate) appears as a recommended treatment for intermediate and high-risk patients. Other indications of prostate brachytherapy (monotherapy and salvage) remain under evaluation. For low-risk patients with good urinary status, low-dose rate brachytherapy alone should be offered. For low-intermediate risk prostate cancer, low-dose rate brachytherapy alone may be offered as monotherapy, while for high-intermediate risk prostate cancer, a combination of external beam radiation therapy (with or without androgen deprivation therapy) plus brachytherapy boost (low- or high-dose rate) should be offered to eligible patients. For patients with high-risk prostate cancer receiving external beam radiation therapy and androgen deprivation therapy, brachytherapy boost (low- or high-dose rate) should be offered to eligible patients. High-dose rate brachytherapy as monotherapy (single dose for low-risk/multifractionated for intermediate and high-risk) must be explored under clinical investigations, as well as salvage brachytherapy for local recurrence.     

Proton-beam therapy for prostate cancer

The treatment options for prostate cancer include prostatectomy, external-beam irradiation, brachytherapy, cryosurgery, focused ultrasound, hormonal therapy, watchful waiting, and various combinations of these modalities. Because the prostate abuts the bladder and rectum, the dose distributions of external-beam irradiations and the accuracy of their placement play crucial roles in the probability of tumor cure and the incidence of posttreatment complications. Principal among the newer radiation technologies is proton-beam therapy (PBT), whose dose distributions make it possible to deliver higher tumor doses and smaller doses to surrounding normal tissues than from x-ray systems. However, as the 10-year cause-specific survival for early-stage disease treated by radiation therapy now exceeds 90%, and with severe late toxicities in the range of 2% to 3%, randomized clinical trials provide the only means to demonstrate improved outcomes from PBT. Short of the data provided by such trials, the efficacy of PBT can be gleaned only from reports in the clinical literature, and, to date, these reports are equivocal. In view of the current health care crisis and the higher costs of PBT for prostate cancer, it is reasonable to assess the viability of this in-vogue but not-so-new technology.     

Brachytherapy for clinically localized prostate cancer

Prostate brachytherapy is an effective treatment option for clinically organ-confined prostate carcinoma. Observed 5- and 10-year follow-up have documented prostate-specific antigen (PSA) levels that were comparable to published radical prostatectomy series and were better than several published external-beam radiation series. Between January 1987 and June 1988, a total of 152 consecutive patients with Stage T1 to T3 low to high Gleason grade prostate cancer were studied at Northwest Hospital in Seattle, Washington. Patients' median age was 70 years (range, 53 to 92 years). All patients received Iodine-125 prostate brachytherapy with or without a 45 Gy dose of external-beam radiation. The average preoperative PSA, clinical stage, and prostate needle biopsy Gleason sum were 11 ng/ml, T2, and (5), respectively, and were known in all but five patients. PSA follow-up, clinical examination, and biopsy results judged disease-free survival at 5 and 10 postoperative years. Elevation of PSA above 0.5 ng/ml or a positive biopsy or a positive bone scan was considered treatment failure. The authors provide an historical review of prostate brachytherapy in conjunction with up-to-date implant techniques and long-term outcome results.     

Curiethérapie de la prostate : évolutions des indications et des techniques

Prostate brachytherapy has been for a long time one of the standard treatments for low risk prostate cancer, with high rates of biochemical control and low levels of urinary and sexual late toxicity compared to other available techniques, namely external beam radiotherapy and radical prostatectomy. The aim of this article is to review the recent innovations of prostate brachytherapy, which suggest a bright future for the technique. We will discuss the extension of indications of permanent implant brachytherapy to favorable intermediate-risk patients, the use of novel isotopes such as Palladium 103 and Cesium 131, and the benefit of brachytherapy as a boost following external beam radiotherapy for intermediate and high-risk patients. We will also discuss the rise of high dose rate brachytherapy, as a boost or monotherapy, the increasing use of MRI for patient selection and treatment planning, as well as the development of brachytherapy as a means of focal therapy.     

Intensity-modulated radiation therapy for prostate cancer

Prostate cancer is among the most common solid malignancies. A number of treatment alternatives exist for localized prostate cancer, including observation, prostatectomy, brachytherapy, and external-beam radiation therapy (EBRT). External-beam radiation therapy has changed dramatically during the past several years. Older techniques paved the way for 3-dimensional conformal radiation therapy (CRT), which in turn facilitated the introduction of intensity-modulated radiation therapy (IMRT). The prostate has served as a model disease site for the implementation of IMRT. As indicated by a growing body of experience, IMRT for prostate cancer represents a major technologic and clinical advance for radiation therapy. In this article, a review is provided of the evolution of EBRT leading to IMRT, the unique features making the prostate an ideal disease site for employing IMRT, the details of the clinical implementation of prostate IMRT and supporting technologic advancements, and the currently reported clinical outcomes of IMRT in prostate cancer. In addition, future directions of prostate IMRT, both technologic and clinical, are discussed.     

Technological advances in radiotherapy for the treatment of localised prostate cancer

There is good evidence that radiation dose escalation in localised prostate cancer is associated with increased cell kill. The traditional two-dimensional (2D) technique of treatment planning and delivery is limited by normal tissue toxicity, such that the dose that can be safely delivered to the prostate by external beam radiotherapy is 65-70 Gy. Several technological advances over the last 20 years have enhanced the precision of external beam radiotherapy (EBRT), and have resulted in improved outcomes. The three-dimensional conformal radiotherapy (3D-CRT) approach reduces the dose-limiting late side-effect of proctitis and has allowed for dose escalation to the whole prostate to 78 Gy. More recently, intensity modulated radiotherapy (IMRT), an advanced form of conformal therapy, has resulted in reduced rectal toxicity when using doses greater than 80 Gy. In addition, IMRT can potentially escalate the dose to specific parts of the prostate where there are resistant subpopulations of tumour clonogens, or can be used to extend the high-dose region to pelvic lymph nodes. The addition of androgen deprivation to conventional radiotherapy has an impact on survival and local control. Initial hormone therapy causes cytoreduction of the prostate cancer allowing for a reduction in radiotherapy volume as well as an additive effect on cell kill. Long-term adjuvant androgen deprivation has been shown to improve overall survival in more advanced tumours. Prostate brachytherapy is now a recognised treatment for those with low-risk disease. It achieves similar long-term outcome to other treatment modalities. Brachytherapy can be used as monotherapy for localised disease, or as boost treatment following conventional EBRT for locally advanced disease. New techniques are available to improve the precision of both target definition and treatment verification. This so-called image-guided radiotherapy will help to enhance the accuracy of dose delivery by correcting both for inter-fraction positional variation and for intra-fraction movement of the prostate in real-time and will allow for tighter tumour margins and avoidance of normal tissues, thereby enhancing the safety of treatment.     

Role of high dose rate brachytherapy in the treatment of prostate cancer

High dose rate (HDR) brachytherapy in intermediate and high-risk prostate cancer patients has started in the late eighties in Europe and the United States, as a boost combined with external beam radiation therapy, as an attractive method for dose escalation. The results of the first dose-escalation study performed at William Beaumont Hospital has established the safety and efficacy of this combined treatment approach. Likewise, this landmark study enabled a paradigm shift in the radiobiology of prostate cancer, demonstrating that the alpha/beta of prostate cancer was much lower than previously believed to be and therefore the sensitivity of this tumor model to higher-than-conventional doses per fraction led to a dramatic increase of hypofractionated treatment regimens, the object of significant clinical research efforts, currently under way. The excellent toxicity profile and clinical outcome of HDR boost combined treatment prompted investigators to expand HDR brachytherapy indications to low/intermediate prostate cancer patients as the sole treatment modality. The results, toxicity and a brief review of the literature for both HDR boost and HDR monotherapy will be presented.     

Interstitial brachytherapy should be standard of care for treatment of high-risk prostate cancer

High-risk prostate cancer represents a therapeutic challenge for both the urologist and radiation oncologist. Biochemical outcomes with radical prostatectomy and external-beam radiation therapy are poor in this subset of patients. These unfavorable results have led some to believe that high-risk prostate cancer is not curable with conventional treatment approaches, which has been an impetus for many of the current trials using neoadjuvant chemotherapy and prostatectomy. With the established efficacy of interstitial brachytherapy, these efforts are likely excessive. Most modern trials indicate excellent biochemical control rates among high-risk patients treated with an aggressive locoregional approach that includes brachytherapy. A thoughtful review of the literature would suggest that interstitial brachytherapy offers a therapeutic advantage over other local treatment modalities and should be considered standard treatment for aggressive organ-confined prostate cancer.