Almost 200,000 new cases of prostate cancer were identified in the United States in 2001.1 Since the introduction of screening with serum prostate specific antigen (PSA), far more of these cancers are being diagnosed when they are small and thus potentially curable. As they are asymptomatic and generally young, the patients are particularly interested in minimally morbid treatments, and many options now are available. Most depend heavily on imaging to locate the tumor and define its position in relation to nearby structures.
Precise External-Beam Irradiation
External-beam radiation has long been one of the two primary treatments for prostate cancer. It also was used postoperatively in patients with positive surgical margins at radical prostatectomy. In its original form, it was often highly morbid, causing urethral and rectal injury. One reason became apparent when it was discovered that the gland can move as much as 1 cm from one day to the next. Therefore, today, conformal radiation and intensity-modulated radiation therapy (IMRT) are given.
Cancer of the prostate was one of the first uses of conformal radiation. The tumor position and configuration are defined, usually by three-dimensional CT, and the precise shape of the tumor is determined. Metal markers can be placed in the gland for daily determination of prostate position. Most recently, a combination linear accelerator and CT scanner has been developed for daily confirmation of gland position.
Repeated imaging also is integral to IMRT. An image of the tumor is captured in three dimensions with one or more modalities and registered in a coordinate system. The tumor and the organs at risk are marked on the image, and the desired radiation dose is indicated for each volume. Iterative simulations are run until the delivery plan is considered optimal. IMRT is now routine for external-beam irradiation of the prostate at many medical centers. An example of the excellent results has been published by Memorial Sloan-Kettering Cancer Center in New York, where almost 800 men were treated.2 The 3-year actuarial likelihood of significant rectal toxicity was only 4% and that of significant urinary toxicity was 15%.
Direct implantation of seeds of iodine 125 or palladium 103 makes radiation therapy an almost totally outpatient procedure and has been sought by thousands of men with prostate cancer since reports of the technique were published in the business press. Two methods have been described for determining where the seeds should be placed. In one, transrectal ultrasonography captures images of the prostate at 5-mm intervals, and the tumor, rectum, bladder, and urethra are marked. The images are digitized, and treatment-planning software determines the appropriate sites for the seeds. Because passage of the delivery needles causes distortion of the prostate, ultrasonography or fluoroscopy monitoring is required for accurate placement. A CT scan is obtained to confirm proper seed position.3 Another method makes use of three-dimensional ultrasonography and software that calculates the number of seeds necessary to irradiate the entire tumor and the radiation doses that will be delivered to the tumor and normal tissue. After the seeds have been implanted, a CT scan is obtained and fused with a plain radiograph to calculate the dose distribution. Two guidance methods still in the experimental stage are MRI with an endorectal coil combined with intraoperative MR4,5 and a urethral catheter containing an ultrasound transducer.6 Despite initial concerns about inadequate radiation dose or inappropriate seed distribution with brachytherapy, a high disease-free survival rate (77% at 10 years) has been described.7
A variation on this technique is high-dose-rate brachytherapy, in which iridium 192 seeds are placed repeatedly for short periods into tubes implanted in the prostate. The first clinical trial of this method combined it with external-beam radiotherapy and obtained a 5-year disease-specific survival rate of 98%.8
Application of Cold and Heat
Surgeons began experimenting with cold as an operative tool in the middle of the 19th century. Although early efforts sometimes led to severe complications, contemporary cryotherapy is finding a place in cancer treatment. Percutaneous cryoablation has been reported as primary treatment for high-risk prostate cancers, sometimes in combination with external-beam radiation9 or for salvage after radiation failure.10 The probes are inserted through the perineum, and the development of the iceball is monitored by real-time sonography.
In 1866, Busch described the regression of a cancer in a patient who suffered a high fever. This discoverythat heat can kill undesirable cellsis being developed for direct treatment of cancer or to sensitize it to radiation.
Interstitial thermotherapy entails insertion of needle-like energy sources into a tumor and, essentially, cooking it, either as the primary treatment or as an adjunct to radiation.11-13 Several laboratories have designed antenna arrays that deliver electromagnetic waves that will create electrical currents leading to tissue heating secondary to electrical resistance. The challenge is to heat only the tumor. The Ontario Cancer Institute/Princess Margaret Hospital in Toronto has written a treatment planning program that incorporates transrectal ultrasound scans on which the prostate, urethra, and rectum have been outlined. The computer creates a “virtual prostate” into which antennas can be inserted, and the program then calculates the time-temperature history at every site in the gland. If the treatment objectives are not met, ie, the entire tumor is not exposed to sufficient heat or the normal tissue will be heated excessively, the antenna locations can be changed, or the power inputs can be altered. The calculations are then repeated. When the operator is satisfied, the program provides a three-dimensional map of the sites for antenna insertion, which is performed under ultrasound guidance.14 Changes in ultrasound attenuation,15,16 contrast-enhanced ultrasonography,17 CT,18 and gadolinium-enhanced MR are all being studied as methods of real-time treatment control.
Interstitial self-regulating rods are experimental devices fabricated to become heated to a specific temperature (called the Curie temperature) when subjected to an alternating magnetic field. For prostate cancer, rods of palladium and cobalt are inserted with ultrasonic or fluoroscopic guidance using a brachytherapy treatment-planning procedure and template. The rods remain in place, so treatment can be repeated if necessary.
Until relatively recently, imaging had little place in the management of prostate cancer. Its primary role was to determine whether the man had bony metastases and thus was not a suitable candidate for radical surgery or radiation. Today, the management of many patients depends critically on imaging. As ablative and other minimally invasive therapies are refined, imaging will become even more important.
Judith Gunn Bronson, MS, is a contributing writer for Decisions in Axis Imaging News.
- Cancer Facts and Figures, 2001. Atlanta: American Cancer Society; 2001.
- Zelefsky MJ, Fuks Z, Hunt M, et al. High-dose intensity modulated radiation therapy for prostate cancer: early toxicity and biochemical outcome in 772 patients. Int J Radiat Oncol Biol Ther. 2002;53:1111 1116.
- Wallner K, Blasko JC, Cavanagh W. Brachytherapy in the management of prostate cancer. In: D Amico AV, Hanks GE, eds. Radiotherapeutic Management of Prostate Adenocarcinoma. London: Arnold; 1999:135 149.
- Hirose M, Bharatha A, Hata N, et al. Quantitative MR imaging assessment of prostate gland deformation before and during MR imaging-guided brachytherapy. Acad Radiol. 2002;9:906 912.
- Bharatha A, Hirose M, Hata N, et al. Evaluation of three-dimensional finite element-based deformable registration of pre- and intraoperative prostate imaging. Med Phys. 2001;28:2552 2560.
- Holmes DR III, Davis BJ, Robb RA. 3D localization of implanted radioactive sources in the prostate using trans-urethral ultrasound. Stud Health Technol Inform. 2001;81:199 205.
- Ragde H, Grado GL, Nadir BS. Brachytherapy for clinically localized prostate cancer: thirteen-year disease-free survival of 769 consecutive prostate cancer patients treated with permanent implants alone. Arch Esp Urol. 2001;54:739 747.
- Deger S, Boehmer D, Turk I, et al. High dose rate brachytherapy of localized prostate cancer. Eur Urol. 2002;41:420 426.
- Benoit RM, Cohen JK, Miller RJ. Cryosurgery for prostate cancer: new technology and indications. Curr Urol Rep. 2000;1:41 47.
- Onik G. Image-guided prostate cryosurgery: state of the art. Cancer Control. 2001;8:522 531.
- Vernon CC, Hand JW, Field SB, et al. Radiotherapy with or without hyperthermia in the treatment of superficial localized breast cancer: results from five randomized controlled trials. Int J Radiat Oncol Biol Phys. 1996;35:731 744.
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- Sneed PK, Stauffer PR, McDermott MW, et al. Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme. Int J Radiat Oncol Biol Phys. 1998;40:287 295.
- Sherar MD, Gertner MR, Yue CK, et al. Interstitial microwave thermotherapy for prostate cancer: method of treatment and results of a Phase I/II trial. J Urol. 2001;166:1707 1714.
- Bevan PD, Sherar MD. B-scan ultrasound imaging of thermal coagulation in bovine liver: log envelope slope attenuation mapping. Ultrasound Med Biol. 2001;27:379 387.
- Bevan PD, Sherar MD. B-scan ultrasound imaging of thermal coagulation in bovine liver: frequency shift attenuation mapping. Ultrasound Med Biol. 2001;27:809 817.
- Gertner MR, Sherar MD, O’Malley ME, et al. Contrast enhanced Doppler ultrasound to assess interstitial microwave thermal therapy (IMTT) for localized prostate cancer [abstract]. Proceedings of the 56th Annual Meeting of the Canadian Urological Association, 2001.
- Purdie TG, Lee T-Y, Iizuka M, Sherar MD. Dynamic contrast enhanced CT measurement of blood flow during interstitial laser photocoagulation: comparison with an Arrhenius damage model. Phys Med Biol. 2000;45:1115 1126.