Radiotherapy as a Treatment of the Primary Tumor 12321 EBRT

In order to deliver the radiation dose to the tumor there are two options: external beam radiotherapy (EBRT) or brachytherapy.

By using external megavoltage radiation beams a relatively homogeneous dose is delivered to the target region. Tissue equivalent bolus is often required to provide sufficient dose build-up to the surface of the lesion. Normal tissues can be spared by using fractionated treatment schedules. Although superficial radiotherapy for CIS has been described using a fractionation scheme similar to that for skin cancer (3540 Gy/10 fractions over 2 weeks), EBRT is more appropriate in locally advanced cases. In order to avoid radiation damage to the adjacent skin, the penis is housed in a wax or Perspex cylindrical block (approximately 10 x 10 cm) which maintains the penis in a suitable upright position. The most commonly utilized fractionation scheme consists of 2-Gy daily fractions for a total dose of 60-66 Gy using two opposed beams over a 6 week period. During the treatment period, penile edema may develop and therefore the cylindrical blocks have to be upsized.

External beam treatment as a single treatment modality has been used in only a small number of studies, most of these reporting on limited numbers of patients.29,30 One exception is a study by Gotsadze et al. analyzing results in 155 patients.31 This study reported local control rates for stages I and II ranging from 65% to 90%. Sarin et al. analyzed the impact of various radiation parameters such as total dose, dose per fraction, total treatment time and "Biological Equivalent Dose" (BED) with or without time, factor on local failure in 44 patients with T1 tumors. A higher incidence of local failure was observed with a total dose less than 60 Gy, dose per fraction less than

2 Gy, and treatment time exceeding 45 days.32 The difference approached prognostic significance (p = 0.052). The incidence of complications such as urethral stricture or stenosis has been reported to be 16%-49%. A further two studies have reported on erectile function which is preserved in up to 90% of the patients.33,34

12.3.2.2 Brachytherapy

Brachytherapy (brachy is Greek for short distance) consists of placing sealed radioactive sources very close to or in contact with the tumor. Because the absorbed dose falls off very rapidly with an increasing distance from the sources, high doses can be delivered safely to a localized target region over a short time. Compared to external beam radiation, the volume of the area treated to a high dose is smaller, but the dose in homogeneity within this volume is more pronounced. By carefully selecting cases, lesions are treated using 2-3 parallel planes of needles which are held in place with predrilled Lucite templates. The geometry and dosimetry follow the Paris system (Fig. 12.1). The intersource and interplane spacing ranges from 12 to 18 mm. The planes are orientated so that the needles pass from the dorsal surface to the ventral surface of the glans. The needle placement can be performed under regional or general anesthesia and takes up to 45 min. The prescribed dose is 60 Gy, which is delivered at a rate of 50-65 cGy per hour over 4-5 days. A low dose rate implant (LDR) can be performed using Iridium-192 wires. Alternatively an automated pulse dose rate (PDR) machine (Nucletron micro Selectron PDR) using a high intensity Iridium-192 source (0.3-1 Ci) can be used.

The brachytherapy needles are well tolerated and patients are catheterized and remain on bed rest with thromboprophylaxis measures (antiembolic stockings and

Fig. 12.1 Interstitial brachytherapy according to the Paris system (With kind permission from Springer Science+Business Media: Crook et al.36 Fig. 1. Courtesy of Professor Juanita Crook, University of British Columbia)

60 Gy isodose catheter

Styrofoam collar Lucite template

Fig. 12.1 Interstitial brachytherapy according to the Paris system (With kind permission from Springer Science+Business Media: Crook et al.36 Fig. 1. Courtesy of Professor Juanita Crook, University of British Columbia)

60 Gy isodose catheter

Styrofoam collar Lucite template o a. o o a. o

Local Failure Free Survival (Years)

Fig. 12.2 Local failure-free survival following interstitial brachytherapy (With kind permission from Springer Science+Business Media: Crook et.al.36 Fig. 2)

Local Failure Free Survival (Years)

Fig. 12.2 Local failure-free survival following interstitial brachytherapy (With kind permission from Springer Science+Business Media: Crook et.al.36 Fig. 2)

subcutaneous heparin). Moist desquamation of the treated area normally peaks at 2-3 weeks after the needles have been removed. Healing occurs after 2-3 months.

Results of brachytherapy have been reported in about 20 studies. All except two of these studies report on fewer than 80 patients (Table 12.1). The largest study by Rozan et al.35 reported on 259 patients of whom 184 had been treated by brachytherapy only and 75 had a combination of external beam radiation and brachytherapy. Crook et al. reported a local failure-free survival of 87.3% at 5 years and 72.3% at 10 years36 (Fig. 12.2). Approximately two-thirds of local failures occur within 2 years with the remainder occurring after 5 years. De Crevoisier et al. reported a local recurrence rate of 20% at 8 years and a cause-specific survival of 90% at 10 years.37

In the vast majority of the studies, the patients have been treated in a period exceeding several decades. Treatment parameters such as tumor dose, dose rate, fractionation schedule, etc. have varied considerably among the patients reported within the individual studies. Also patient selection criteria have not been uniformly applied in most of the reports. Despite this wide variety in treatment parameters and patient characteristics, the outcome of the studies is remarkably concordant.33,37,38 Long-term (5-10 years) local control rates vary between 60 and 90% and seem more related to tumor characteristics than treatment parameters. Adequate surgical salvage is still possible with a success rate between 70 and 100% and reported penis preservation rate is between 52 and 86%. The most important predictors for successful brachyther-apy seem to be the tumor size (less than 4 cm) and tumor location limited to the glans or the prepuce without corpus cavernosum involvement. For patients meeting these criteria, the different studies report local recurrence rates of about 20% after 5-10 years with a secondary control of about 85% of the recurrences by salvage surgery.

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