Significant advancements in radiation oncology have led to increased use of radiotherapy for localized and advanced prostate cancer. This approach produces higher cure and control rates and reduced rates of side effects such as incontinence, rectal injury and erectile dysfunction. The primary strategy behind radiation therapy has been to deliver higher doses more accurately to a targeted cancer — while sparing healthy adjacent tissue to avoid treatment-related complications.

Numerous dose escalation studies over the past decade have demonstrated lower recurrence rates for patients who receive higher doses of radiation. Intensity-modulated radiation therapy (IMRT) has revolutionized the delivery of radiation therapy by permitting dose escalation with precise tumor targeting while significantly limiting the radiation dose to surrounding normal tissue and critical structures using sophisticated computer optimization algorithms that address site-specific treatment issues in the pelvis.^1-3 When used in combination with permanent interstitial prostatic brachytherapy (the permanent placement of radioactive sources directly into prostate tissue), maximal tumoricidal intraprostatic doses are achieved. In addition, doses are delivered in surrounding periprostatic tissue to address the issue of possible microscopic extracapsular extension of cancer — all with little to no additional urinary or rectal side effects.

Use of IMRT

IMRT represents a new treatment paradigm that involves multimodality imaging of computed tomography (CT), magnetic resonance imaging (MRI), three-dimensional ultrasound and positron emission testing (PET).

These technologies can be fused with treatment planning software to control for treatment setup uncertainties and internal organ motion of respiration and digestion, as well as tumor control probabilities and normal tissue complication probabilities.^4-6 IMRT has the unique ability to modify the radiation dose a tumor receives while treatment is being delivered. Rather than a single beam, the radiation beam is divided into thousands of multiple beams (or beamlets), each with its own intensity and energy level as prescribed by the radiation oncologist. These beamlets treat small areas of tissue called voxels, which are a cubic millimeter of space. Each voxel potentially receives a different dose within a specified treatment field.

Simulation is the physical treatment planning process for IMRT that uses the multimodality imaging process to three-dimensionally reconstruct a patient's anatomy in the treatment planning software system.^4,5,7 A critical component of the simulation process involves immobilizing the lower body with customized devices such as alpha cradles (a lower body cast or mold) or rectal balloons to ensure positioning accuracy (usually in the supine position) each day and to decrease external motion during treatment.

Once the simulation has been completed, a planning phase, referred to as "inverse treatment planning," generates beam profiles with varying intensities within the treatment field. The intensity profile of each beamlet is then adjusted to the desired specifications of dose to tumor, as well as to surrounding tissues. A computerized optimization program selects the best combination of beamlet intensities to obtain the ideal treatment plan. This sophisticated computerized software generates a specific treatment program for the patient, maximizing dose to the target (prostate with periprostatic margin, possible seminal vesicles or lymph nodes) and minimizing the dose to the rectum, bladder, penile bulb and hips.

Using varying beam intensities, the incidence of "hot spots" or overdosage to thinner tissue is reduced, along with underdosage to thicker tissue. This radiation prescription is considered accurate within 1 mm to 3 mm. Periodic sequential clinical evaluation and imaging are performed by a radiation oncologist and a physicist to refine the plan as desired.^4-6

The actual delivery of the radiation is a dynamic process accomplished with multileaf collimators (MLC). These devices are mounted on a linear accelerator that consists of numerous computer-controlled tungsten leaves or apertures that project a 1x1-cm beam size and move independently of each other to dynamically shift to form-specific patterns to sculpt the beam to targeted tissue and block the beam at specified areas. This device replaces hand-made lead alloy blocks previously used in conventional and 3D conformal radiation.

Before actual treatment begins, the patient undergoes a final check of setup and safety systems. Digitally reconstructed radiographs (DRR) verify patient setup, and the machine gantry (the moving apparatus that rotates around the patient with the MLC attached) is rotated throughout each treatment field (port) to ensure there will be no collision with the table or patient. Lasers are aligned with the tattooed marks placed during simulation.

Treatments are scheduled daily Monday through Friday, and each lasts approximately 15 minutes. Strict quality assurance methods are used to decrease patient motion (external and internal) and ensure treatment accuracy. Setup and verification of the patient prior to each treatment takes minutes, and the treatment itself is delivered by radiation therapists seated at computers outside the treatment room. While the patient is lying in the immobilization device, quality assurance methods may be used. These include the following:^4,5,7,8

Interstitial Brachytherapy

Contemporary implant techniques with and without supplemental external beam radiation therapy have evolved dramatically over the past 15 to 20 years. Technologic advancements have prompted a surge in the use of interstitial brachytherapy. These advances include the introduction of CT scanners, transurethral ultrasound and fluoroscopic guidance, sophisticated computerized treatment planning, refinements of implant techniques (transperineal approach vs. open surgical incision), peripheral seed loading technique, and the development of new radioisotopes such as palladium 103.^9-12

Subsequent to these improvements, bowel and bladder toxicity have been greatly reduced, erectile function has been better preserved, and radiation doses have been optimized for increased survival.^9-12

Transperineal implantation of permanent radioactive seeds is performed on an outpatient basis under local, general or spinal anesthesia, guided by ultrasound and fluoroscopy. The seeds are delivered through small hollow needles inserted through the perineum into the prostate tissue with sharp trochars. The prostate is anchored by placing special anchor needles in specific positions, crisscrossed, to transfix the prostate during the procedure. This prevents prostate motion during the implantation process.

The procedure lasts approximately 1 hour and is performed with the patient supine and his legs in an extended lithotomy position. Prostatic ultrasound and, more recently, 3D color flow Doppler ultrasound allow for real-time imaging and dynamic visualization, providing a more precise image of the prostate and more accurate placement of seeds.

Proper bowel preparation using liquid diets, enemas or laxatives is imperative to clear the rectum of feces and facilitate ultrasound imaging. Predetermined coordinates from the computerized preplan designate the placement of the needles via a custom perineal template anchored to the operating room table, which stabilizes the template and the rectal ultrasound probe. This preplan provides for optimal placement of seeds, desired depth for seeds to be placed, and desired dosing to target tissue.^13,14 Once the seeds have been deposited in the prostate via needles with the aid of an applicator, all placement needles are removed.

An indwelling urinary catheter is placed before implant for monitoring of urine output and provides access for continuous or intermittent bladder irrigation as needed during the hospital stay. Intraoperative management may include the use of corticosteroids and antibiotics and placement of compression stockings. Patients are typically kept overnight for observation, but they may be discharged within hours depending on protocol.^13,14

Patients are rarely sent home with an indwelling catheter. Subsequent quality assurance measures include postimplant dosimetry to confirm proper placement and appropriate radiation dose coverage of target tissue through objective analysis via CT scans.

Treatment Outcomes

The 10-year and 12-year cure rates for combination therapy using brachytherapy and external beam radiation (older studies based on 3D conformal external beam radiation therapy) are encouraging. They are generally equal — and better in some high-risk patients — compared with other treatment modalities.9,11-13 Freedom from biochemical failure, based on achieving a PSA nadir of 0.2 ng/mL or less, is approximately 80% to 90% for intermediate- to high- risk patients.^9,11-13

Symptom Management

The nurse practitioner's role in combination IMRT and interstitial brachytherapy is multifaceted and primarily related to symptom management after seeding (see box on facing page). Patient care involves education about the two-part treatment process and its associated effects. The 5-week course of IMRT produces minimal urinary and bowel irritability, and in most instances these side effects do not require pharmacologic intervention.

In addition to education about the procedure, patients require information about the importance of compliance with the daily treatment schedule, adherence to any dietary recommendations made for urinary or bowel changes, and confirmation of date of seed implant, which is typically performed 2 to 3 weeks after completion of IMRT. Patients are capable of performing all activities of daily living and most exercise programs throughout the IMRT treatments.

Patient care before, during and after brachytherapy should include pretreatment assessments of urinary, bowel and erectile function.

Prebrachytherapy education focuses on the necessity of anesthetic-related pretests, the procedure itself and postbrachytherapy expectations, including radiation safety precautions. Radiation safety policies are specific to individual institutions and may or may not require the straining of urine or retrieval of seeds. Therefore, the patient should be educated that neither stool nor urine is radioactive; only the seeds emit radiation.

Selection of the radioisotope to be used (iodine 125 vs. palladium 103) is also a factor in determining the extent of radiation precautions. Discharge education is crucial to reduce patient anxieties and accurately prepare for anticipated side effects. Patients are discharged with instructions for diet, medications and activity, as well as prescriptions and an appointment for follow-up evaluation.

Emotional support is an important aspect of care. Associated emotional factors, such as anxiety, depression, relationship difficulties, financial hardships, fear and grief, must be determined to address total care needs of the patient and identify any compliance issues with treatment recommendations.

Patient education during all aspects of the treatment process should focus on resolution of knowledge deficits, alleviation of misconceptions and fears, and reinforcement of supportive measures to manage anticipated side effects.

Putting It Into Practice

Over the past 2 decades, significant technologic improvements have been made in radiation therapy treatment protocols and delivery systems. Subsequent higher cure rates and decreased side effects have led patients to seek therapies that will provide the highest likelihood of cure and best quality of life.

A combination protocol of two state-of-the-art forms of radiation therapy, IMRT and transperineal interstitial brachytherapy, offers the added security of addressing possible extracapsular extension of cancer without additional side effects, thus maintaining a higher quality of life.

Physicians are in a unique position to enhance experiences of these patients by discussing available novel treatment options and promoting an encouraging, positive outlook toward side effect management.

References

1. Teh BS, et al. Intensity modulated radiotherapy (IMRT) decreases treatment morbidity and potentially enhances tumor control. Cancer Invest. 2002;20(4):437-451.

2. Hong TS, et al. Intensity-modulated radiation therapy: emerging cancer treatment technology. Br J Cancer. 2005;92(10):1819-1824.

3. Bucci MK, et al. Advances in radiation therapy: conventional to 3D, to IMRT, to 4D, and Beyond. CA: Cancer J Clin. 2005;55(2):117-134.

4. Mohan R, et al. Intensity modulated radiation treatment planning, quality assurance, delivery and clinical application. In: Perez C, et al. Principles and Practice of Radiation Oncology. 4th ed. Philadelphia, Pa.: Lippincott, Williams and Wilkins; 2004: 314-335.

5. Dattoli MJ, et al. Brachytherapy and IMRT. Sarasota, Fla.: Dattoli Cancer Foundation; 2005: 7-47.

6. Oh OE, et al. Comparison of 2D conventional, 3D conformal, and intensity modulated treatment planning techniques for patients with prostate cancer with regard to target-dose homogeneity and dose to critical uninvolved structures. Med Dosim. 1999;24(4):255-263.

7. Jones AO, Kleiman MT. Patient setup and verification for intensity-modulated radiation therapy (IMRT). Med Dosim. 2003;28(3):175-183.

8. Dragun AE, et al. Defining targets and protecting normal tissues in inverse planned IMRT for prostate, head and neck, and gynecologic cancers: a comparative review. Community Oncology. 2005;2(4):299-306.

9. Blasko JC, et al. The role of external beam radiotherapy with I-125/Pd-103 brachytherapy for prostate carcinoma. Rad Oncol. 2000;57(3):273-278.

10. Perez CA, et al. Principles and Practice of Radiation Oncology. 4th ed. Philadelphia, Pa.: Lippincott, Williams & Wilkins; 2004: 604-635,1692-1762.

11. Dattoli M, et al. Long term outcomes after treatment with external beam radiation and palladium 103 for patients with higher risk prostate carcinoma. Cancer. 2003;97(4):979-983.

12. Merrick GS, et al. Biochemical outcome for hormone-naive intermediate risk prostate cancer managed with permanent interstitial brachytherapy and supplemental external beam radiation. Brachytherapy. 2002;1(2):95-101.

13. Wallner K, et al. Brachytherapy Made Complicated. 2nd ed. Washington, D.C.: SmartMedicine Press; 2001: 5-377.

14. Dattoli MJ. Palladium Brachytherapy: Rationale, Design and Evaluation. Sarasota, Fla.: Dattoli Cancer Foundation; 2004: 5-46.

Jennifer Cash is an adult nurse practitioner who specializes in intensity-modulated radiation therapy and interstitial brachytherapy at the Dattoli Cancer Center and Brachytherapy Research Institute in Sarasota, Fla.

Side Effect Management Protocol for Palladium 103 Interstitial Brachytherapy of the Prostate

Skin

Side Effects: bruising of scrotum or perineum; tenderness and discomfort; hematoma

Interventions: