The Use of Chemotherapy and Chemoradiation

Combination therapy in the form of chemotherapy and radiotherapy is utilized in an attempt to improve the long-term outcomes for patients diagnosed with urethral

Penis Needle
Fig. 8.7 Interstitial brachytherapy of the penile urethra using hypodermic needle and plastic template. The penis is kept away from the testicles using a sponge (From Gerbaulet et al.34. Reprinted with permission)

cancer. Multimodality therapy offers the advantage of local and systemic control and facilitates future surgery either in the neoadjuvant setting or as salvage therapy. Radiosensitization of tumors by chemotherapeutic agents appears to enhance the efficacy of EBRT.

Studies have used regimens based on the treatment of anal SCC which uses a combination of Mitomycin C and 5-FU whereas others have used cisplatin and 5-FU based on the common SCC penis regimens. For primary urethral TCC, bladder- based regimens are often used.

Nigro et al. first utilized a neoadjuvant chemoradiation approach in the treatment of SCC of the anus.35 Combined chemoradiation is now the first-line treatment for SCC of the anus. A number of institutions have since chosen to treat primary urethral SCC with the same regimen used for anal SCC due to the similar tumor histology, embryological development, an association with HPV-16, and a high rate of local recurrence.6

This has been investigated in a series of 18 patients treated with a uniform chemoradiation protocol. All 18 patients presented with invasive carcinoma of the

DAY 1

Chemotherapy:

5-FU (IV infusion over 24 hours @ 1000mg/m2) Mitomycin C (IV Bolus @ 10mg/m2)

5-FU (IV infusion over 24 hours @ 1000mg/m2)

Day 29:

5-FU (IV infusion over 24 hours @ 1000mg/m2) Mitomycin C (IV Bolus @ 10mg/m2)

Day 30-32:

5-FU (IV infusion over 24 hours @ 1000mg/m2)

DAY 32

Fig. 8.8 Modified Nigro chemoradiation protocol used by Cohen et al. in the treatment of male primary urethral carcinoma male urethra and were treated with chemotherapy consisting of 5-FU and Mitomycin C with concurrent external beam radiotherapy to the genitalia, perineum, and inguinal and external iliac lymph nodes.6 The treatment schedule is summarized below (Fig. 8.8).

The follow-up was performed at 6 weeks and then every 3-6 months for the first 2 years and biannually thereafter. Salvage surgery was only undertaken in non-responders to initial treatment and those with recurrent disease.

Of the 18 patients, three were nonresponders and died of the disease despite extensive salvage surgery. The remaining 15 patients (83%) experienced a complete response following chemoradiation. Four of the 15 patients experienced local recurrences and underwent further surgery. A total of 10 patients (56%) experienced no recurrences from the primary tumor (5 proximal urethra/5 distal urethra). All 10 patients with no disease recurrence did however develop urethral strictures which required surgical intervention including complex urethral reconstruction in three patients. The 5-year overall and disease-specific survival rate was found to be 60% and 83%, respectively. These results are extremely promising considering that 84% of patients had T3 or T4 disease and that 34% had node-positive disease.6 Cohen and colleagues' approach represents a promising treatment option for male primary urethral carcinomas with effective organ preservation and local disease control.

Radiotherapy:

Total radiation dose: 45-55Gy Primary lesion: additional 12-15Gy Given over 25 fractions

Irradiation sites:

- Primary lesions (genitalia)

- Perineum

- Inguinal lymph nodes

- External iliac lymph nodes

A further study by Gheiler and coworkers showed that disease control could be achieved in 70% of patients with a mean follow-up of 43 months.6 In the 21 patients reported, the best results were found in tumors staged as T3 or above (42%), multi-modality therapy yielded the optimal outcomes with disease-free survival reaching 60%. Surgery alone was found to be the best modality in stage Ta-2N0M0 patients in the same study.

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