Imaging prostate cancer: current and future applications

Various treatment options are available for adenocarcinoma of the prostate--the most common malignant neoplasm among men in the United States. To select an optimum management strategy, we must be able to identify an organ-confined disease (in which local therapy such as surgery or radiation may be beneficial) vs prostate cancer beyond the confines of the gland (for which other treatment approaches may be more appropriate). At present, no standard imaging modality can by itself reliably diagnose and/or stage adenocarcinoma of the prostate. Standard transrectal ultrasound, magnetic resonance imaging (MRI), computed tomography, bone scans, and plain x-ray are not sufficiently reliable when used alone. Fortunately, advances in imaging technology have led to the development of several promising modalities. These modalities include color and power Doppler ultrasonography, ultrasound contrast agents, intermittent and harmonic ultrasound imaging, MR contrast imaging, MRI with fat suppression, MRI spectroscopy, three-dimensional MRI spectroscopy, elastography, and radioimmunoscintigraphy. These newer imaging techniques appear to improve the yield of prostate cancer detection and staging, but are limited in availability and thus require further validation. This article reviews the status of current imaging modalities for prostate cancer and identifies emerging imaging technologies that may improve the diagnosis and staging of this disease.     

Imaging of prostate cancer

PURPOSE OF REVIEW: Appropriate imaging of prostate cancer is a crucial component of staging and therapy application. The purpose of this review is to highlight the most important developments in novel imaging modalities reported in the past year. RECENT FINDINGS: Transrectal ultrasound is used to guide needle biopsy and brachytherapy. Improved results are obtained with color and power Doppler transrectal ultrasound with sonographic contrast agents. The role of elastography in prostate cancer remains to be elucidated. Magnetic resonance imaging is now widely used for staging before treatment and accumulating data indicate the utility of this technique with magnetic resonance spectroscopy in staging and follow-up. Positron-emission tomography alone or especially in combination with computed tomography imaging with the new radiotracers (11)C-choline, (18)F-fluorocholine, (11)C-acetate and (18)F-fluoride have shown promising results. Further investigations in larger clinical studies are necessary to establish the role of these imaging techniques in the management of patients with prostate cancer. SUMMARY: This report provides a summary of novel types of imaging and indicates their promise in prostate cancer.     

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.     

New interstitial HDR brachytherapy technique for prostate cancer: CT based 3D planning after transrectal implantation.

We have developed a new interstitial HDR brachytherapy technique for the treatment of prostate cancer using CT based 3D planning after transrectal implantation of four non-parallel needles. CT based needle reconstruction, target definition, evaluation and documentation, including DVHs and 3D imaging, is a feasible, safe and well tolerated treatment concept.     

Inverse treatment planning based on MRI for HDR prostate brachytherapy

PURPOSE: To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. METHODS AND MATERIALS: Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. RESULTS: We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of <5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of <2% (mean 0.54%). CONCLUSION: Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints in our procedure reduced uncertainty in planning and treatment.     

State-of-the-art uroradiologic imaging in the diagnosis of prostate cancer

In the diagnostic process of prostate cancer, several radiologic imaging modalities significantly contribute to the detection and localization of the disease. These range from transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) to positron emission tomography (PET). Within this review, after evaluation of the literature, we will discuss the advantages and disadvantages of these imaging modalities in clarifying the patient's clinical status as to whether he has prostate cancer or not and if so, where it is located, so that therapy appropriate to the patient's disease may be administered. TRUS, specifically with the usage of intravenous contrast agents, provides an excellent way of directing biopsy towards suspicious areas within the prostate in the general (screening) population. MRI using functional imaging techniques allows for highly accurate detection and localization, particularly in patients with prior negative ultrasound guided biopsies. A promising new development is the performance of biopsy within the magnetic resonance scanner. Subsequently, a proposal for optimal use of radiologic imaging is presented and compared with the European and American urological guidelines on prostate cancer.     

Imaging modalities for prostate cancer

Prostate cancer is the most frequently diagnosed malignancy in the Western male population and the associated socioeconomic impact on healthcare is of great concern. Since the early 1990s, MRI has evolved into an important diagnostic imaging modality for prostate cancer patients. In this review, the applications of diagnostic imaging modalities in prostate cancer, such as transrectal ultrasound, computed tomography and MRI are described. The clinical value of these techniques in prostate cancer detection, localization, characterization, staging and active surveillance are discussed.     

Use of TRUS to predict pubic arch interference of prostate brachytherapy

PURPOSE: To demonstrate the potential for transrectal ultrasound (TRUS) to predict pubic arch interference of transperineal needle placement for prostate brachytherapy. METHODS AND MATERIALS: TRUS and pelvic computerized tomography (CT) scans from 22 patients who had transperineal prostate brachytherapy at University of Washington were analyzed for pubic arch visualization and interference. The outer margins of the prostate and the inner margins of the pubic bones from each imaging modality were outlined and compared. RESULTS: The pubic arch was readily visualized by TRUS in 21 of the 22 patients. There was good correlation between TRUS and CT for evaluating the amount of pubic arch interference (r = 0.90). CONCLUSION: TRUS can be substituted for CT imaging to evaluate pubic arch interference of transperineal needle placement for prostate brachytherapy. Eliminating routine CT scanning would reduce the cost of treatment.     

前列腺肿物检查方法的临床评价

目的评价血清前列腺特异性膜抗原（PSA）和各项物理检查对指导前列腺活检的意义。方法结合血清PSA、直肠指诊（DRE）、直肠B超（TRUS）及磁共振成像（MRI）检查,对148例可疑前列腺病变患者,经直肠B超引导下行前列腺穿刺活检。结果前列腺活检阳性率为43.9%（65/148）。DRE和PSA对前列腺癌的诊断有意义(P＜0.05),其中PSA加DRE、TRUS及MRI对前列腺癌的诊断明显高于PSA或DRE（P<0.01）,但前述三者之间对前列腺癌的诊断差异无显著性（P=0.46,P＝0.16,P＝0.52）。MRI的敏感性高于DRE和TRUS（P=0.05,P=0.01）,TRUS的特异性高于PSA或MRI（P=0.02,P=0.001）。结论前列腺活检是诊断前列腺癌的重要手段,其初步筛选以DRE加PSA为主,同时结合TRUS及MRI,可提高筛选的敏感性和特异性,避免不必要的活检。DRE或PSA加TRUS或MRI在前列腺活检筛选中可提高前列腺活检的阳性率。     

Intraoperative planning and evaluation of permanent prostate brachytherapy: Report of the American Brachytherapy Society

Purpose: The preplanned technique used for permanent prostate brachytherapy has limitations that may be overcome by intraoperative planning. The goal of the American Brachytherapy Society (ABS) project was to assess the current intraoperative planning process and explore the potential for improvement in intraoperative treatment planning (ITP).

Methods and Materials: Members of the ABS with expertise in ITP performed a literature review, reviewed their clinical experience with ITP, and explored the potential for improving the technique.

Results: The ABS proposes the following terminology in regard to prostate planning process: • Preplanning—Creation of a plan a few days or weeks before the implant procedure. • Intraoperative planning—Treatment planning in the operating room (OR): the patient and transrectal ultrasound probe are not moved between the volume study and the seed insertion procedure. • Intraoperative preplanning—Creation of a plan in the OR just before the implant procedure, with immediate execution of the plan. • Interactive planning—Stepwise refinement of the treatment plan using computerized dose calculations derived from image-based needle position feedback. • Dynamic dose calculation—Constant updating of dose distribution calculations using continuous deposited seed position feedback. Both intraoperative preplanning and interactive planning are currently feasible and commercially available and may help to overcome many of the limitations of the preplanning technique. Dosimetric feedback based on imaged needle positions can be used to modify the ITP. However, the dynamic changes in prostate size and shape and in seed position that occur during the implant are not yet quantifiable with current technology, and ITP does not obviate the need for postimplant dosimetric analysis. The major current limitation of ITP is the inability to localize the seeds in relation to the prostate. Dynamic dose calculation can become a reality once these issues are solved. Future advances can be expected in methods of enhancing seed identification, in imaging techniques, and in the development of better source delivery systems. Additionally, ITP should be correlated with outcome studies, using dosimetric, toxicity, and efficacy endpoints.

Conclusion: ITP addresses many of the limitations of current permanent prostate brachytherapy and has some advantages over the preplanned technique. Further technologic advancement will be needed to achieve dynamic real-time calculation of dose distribution from implanted sources, with constant updating to allow modification of subsequent seed placement and consistent, ideal dose distribution within the target volume.     

GEC/ESTRO-EAU recommendations on temporary brachytherapy using stepping sources for localised prostate cancer.

BACKGROUND AND PURPOSE: The aim of this paper is to present the GEC/ESTRO-EAU recommendations for template and transrectal ultrasound (TRUS) guided transperineal temporary interstitial prostate brachytherapy using a high dose rate iridium-192 stepping source and a remote afterloading technique. Experts in prostate brachytherapy developed these recommendations on behalf of the GEC/ESTRO and of the EAU. The paper has been approved by both GEC/ESTRO steering committee members and EAU committee members. PATIENTS AND METHODS: Interstitial brachytherapy (BT) to organ confined prostate cancer can be applied as a boost treatment in combination with external beam radiation therapy (EBRT) using a proper number of BT fractions in curative intent. Temporary transperineal BT alone or in combination with EBRT are feasible as a palliative/salvage treatment modality because of local recurrence, however, without large clinical experience. The use of temporary BT as a monotherapy is subject of ongoing clinical research. RESULTS: Recommendations for pre-treatment investigations, patient selection, equipment and facilities, the clinical team, the implant procedure (treatment planning and needle implantation) dose and fractionation, reporting, management of side effects and follow-up are given. CONCLUSIONS: These recommendations are intended to be technically and advisory in nature, but the ultimate responsibility for the medical decision rests with the treating physician. Although, this paper represents the consensus of an interdisciplinary group of experts, TRUS and template guided temporary transperineal interstitial implants in prostate cancer are a constantly evolving field and the recommendations are subject to modifications as new data become available.     

Feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods.

BACKGROUND AND PURPOSE: The purpose of this study is to investigate the feasibility of adequate dose coverage in permanent prostate brachytherapy using divergent needle insertion methods. These methods can be useful in magnetic resonance imaging (MRI) guided needle insertion techniques to avoid pubic arch interference. METHODS AND MATERIALS: MRI data were collected from 10 patients with T1-T2 prostate cancer. An inverse planning algorithm based on simulated annealing was used to optimize the dose distribution for three needle insertion methods: divergent needles with a single rotation point, divergent needles with a double rotation point, and current parallel needle insertion method. The dose constraints were based on our clinical criteria and the recent ESTRO/EAU/EORTC recommendations. RESULTS: If the planning target volume (PTV) surrounded the prostate and only intraprostatic seeds were allowed, the mean PTV volume that received 100% of the prescribed dose (V(100)) was 99% for all needle insertion methods. If the PTV was increased to the prostate with a 3mm margin, the mean PTV V(100) equalled 94%, 95%, and 94% for the single rotation point, double rotation point and current parallel needle insertion method, respectively. If in the latter case the tips of the seeds were placed 3mm outside the apex and base of the prostate, the mean PTV V(100) was 96% for all needle insertion methods. CONCLUSION: This planning study shows that it is feasible to generate an adequate dose coverage using divergent needle insertion methods.     

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.     

MRI-guided HDR prostate brachytherapy in standard 1.5T scanner

PURPOSE: Magnetic resonance imaging (MRI) provides superior visualization of the prostate and surrounding anatomy, making it the modality of choice for imaging the prostate gland. This pilot study was performed to determine the feasibility and dosimetric quality achieved when placing high-dose-rate prostate brachytherapy catheters under MRI guidance in a standard "closed-bore" 1.5T scanner. METHODS AND MATERIALS: Patients with intermediate-risk and high-risk localized prostate cancer received MRI-guided high-dose-rate brachytherapy boosts before and after a course of external beam radiotherapy. Using a custom visualization and targeting program, the brachytherapy catheters were placed and adjusted under MRI guidance until satisfactory implant geometry was achieved. Inverse treatment planning was performed using high-resolution T(2)-weighted MRI. RESULTS: Ten brachytherapy procedures were performed on 5 patients. The median percentage of volume receiving 100% of prescribed minimal peripheral dose (V(100)) achieved was 94% (mean, 92%; 95% confidence interval, 89-95%). The urethral V(125) ranged from 0% to 18% (median, 5%), and the rectal V(75) ranged from 0% to 3.1% (median, 0.3%). In all cases, lesions highly suspicious for malignancy could be visualized on the procedural MRI, and extracapsular disease was identified in 2 patients. CONCLUSION: High-dose-rate prostate brachytherapy in a standard 1.5T MRI scanner is feasible and achieves favorable dosimetry within a reasonable period with high-quality image guidance. Although the procedure was well tolerated in the acute setting, additional follow-up is required to determine the long-term safety and efficacy of this approach.     

Permanent prostate brachytherapy in men with clinically localised prostate cancer

Permanent prostate brachytherapy techniques are associated with excellent biochemical control for patients with localised prostate cancer. Ten-year data show that permanent prostate brachytherapy is compatible with external beam irradiation or radical prostatectomy. However, treatment protocols and techniques for prostate brachytherapy vary between centres and there is little conformity of treatment protocols. The selection of patients for monotherapy or combined external beam irradiation and brachytherapy is controversial. The role of neoadjuvant androgen deprivation also remains unanswered in patients with localised prostate cancer. In addition, post-implant dosimetry may in fact be more significant for predicting outcome than the addition of adjuvant therapies, and should be a requirement when performing prostate brachytherapy. Data now seem to support specific computed tomography (CT)-based criteria to evaluate implant quality and delivered dose to the prostate. Unfortunately, prostate oedema and poor imaging techniques are limiting factors for evaluating implant dosimetry. Treatment planning techniques that use new treatment planning computers may assist in improving the implant procedure and dosimetry and are now available.     

Ultrasonography and fluoroscopic fusion for prostate brachytherapy dosimetry

: To investigate the feasibility of performing postimplant and intraoperative dosimetry for prostate brachytherapy by fusing transrectal ultrasound (TRUS) and fluoroscopic data.

: Registration of ultrasound (prostate boundary) and fluoroscopic (seed) data requires spatial markers that are detectable by both imaging modalities. In this study, the needle tips were considered as such fiducials. Prostate phantoms were implanted with the seeds, and four localization needles were inserted. In the TRUS frame of reference, the longitudinal coordinate of the needle tip was determined by advancing the needle until the echo from its tip just registered at a known probe depth. The tip’s transverse coordinates were determined from the associated TRUS slice. The three-dimensional needle tip positions were also calculated in the fluoroscopic coordinate system using a seed reconstruction method. The transformation between the TRUS and fluoroscopy coordinate systems was established by the least-squares solution using the singular value decomposition.

: With three of four needle tips as fiducials and the one remaining needle as a test target, the mean fiducial registration error was 0.8 mm and the test target registration error was 2.5 mm. When all four points were used for registration, the errors decreased to 1.1 mm. A comparison between the proposed method and CT-based dosimetry yielded a percentage of prostate volume receiving 100% and 150% of the prescribed minimal peripheral dose and minimal dose received by 90% of the prostate gland that agreed within 0.4%, 2.7%, and 4.2%, respectively.

: The combination of TRUS and fluoroscopy is a feasible alternative to the currently used CT-based postimplant dosimetry. Furthermore, because of online imaging capability, the method lends itself to real-time intraoperative applications.     

Ultrasound image fusion for external beam radiotherapy for prostate cancer

: To determine whether real-time ultrasound imaging and targeting system for the treatment of prostate cancer was feasible. The initial phase of this project included a study to develop and determined (a) software for the fusion of ultrasound images to standard x-rays obtained during simulation, and (b) the potential reduction in field size with real time imaging.

: During 13 patient simulations a transrectal ultrasound image was obtained. Orthogonal x-ray films were acquired with the rectal probe in place. Both the x-ray and ultrasound images were digitized and a fusion image was created of the prostate position in relation to the probe, bladder, and rectum. The two-dimensional area of the rectum, bladder, and prostate was determined in the lateral projection. Potential conformal blocks were designed for the lateral portals in a four-field treatment technique.

: The transrectal ultrasound probe enabled real-time prostrate imaging. The lateral field size can be reduced to 6.08 × 5.68 cm² ± 0.62 × 0.48 cm² from the standard 8 × 8 cm² field. The posterior rectal wall was physically displaced out of the lateral field. The area of the rectum included in the lateral field in 1.75 cm² ± 0.85 cm².

: The prostate position can be determined with certainty on a regular basis with transrectal ultrasonography. The amount of normal tissue in the high dose volume can be reduced. This approach may reduce acute and chronic morbidity and allow further dose escalation.     

ORIGINAL ARTICLE: Use of 3D imaging and awareness of GEC-ESTRO recommendations for cervix cancer brachytherapy throughout Australia and New Zealand

Introduction: A 2005 survey of practices indicated limited use of three-dimensional (3D) imaging modalities and planning methods in cervix cancer brachytherapy in Australia and New Zealand. However, advancing technologies and published recommendations are influencing change. This survey aims to identify both changes in practice and awareness and uptake of Groupe European de Curietherapie of the European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) recommendations. Methods: A survey was emailed to all radiotherapy departments with brachytherapy facilities. Twenty departments practise brachytherapy for cancer of the cervix. The survey consisted of five questions enquiring about use and type of 3D imaging; rate of reimaging and replanning; and contouring, prescribing and reporting practices. Results: A 100% response rate was obtained. Sixty-five per cent of departments use 3D CT imaging to plan brachytherapy insertions. Thirty per cent of departments use two-dimensional (2D) x-rays. Four departments (20%) use a combination of imaging modalities including CT, ultrasound and MRI. Sixty-five per cent of departments reimage and replan for each insertion. Four departments (20%) contour, prescribe dose and report treatment according to GEC-ESTRO recommendations. Conclusions: There has been a marked increase in the use of 3D imaging and awareness of GEC-ESTRO recommendations. Implementation and reporting of image-based gynaecological brachytherapy is strongly dependent on local resources and infrastructure.