eMedicine Specialties > Otolaryngology and Facial Plastic Surgery > Head & Neck Surgery
Postcricoid Area, Malignant Tumors: Follow-up
Updated: Jun 28, 2006
Outcome and Prognosis
Survival figures for postcricoid carcinoma vary widely. This divergence, in part, may be ascribed to early literature written during the transition of radiation treatments from kilovoltage to megavoltage. Additionally, treatment philosophies differ from country to country and even within the United States. The treatment protocol at the University of Florida uses twice-a-day hyperfractionated radiotherapy to a total dose of 68-72 Gy. Many other centers in the United States administer single-daily fractions of approximately 2 Gy but achieve total doses in the same 68- to 72-Gy range. India and Great Britain tend to use daily doses of 3 Gy to a total dose of 50-55 Gy. These treatment philosophies seem to reflect the collective opinion that hyperfractionated therapy improves survival.
With this in mind, the large retrospective studies dedicated to postcricoid carcinoma emanate from the United Kingdom and India. Reported overall 5-year survival rates range from 7.8-43%. Cited mortality rates of untreatable disease are 50% at 9 weeks and 95% at 30 weeks. The reports define untreatability as tumors larger than 5 cm in longest dimension with true vocal cord fixation, paravertebral muscle invasion, and carotid invasion.
Using tumor stage as a stratification factor, Farrington et al (with a 40- to 50-patient sample for each stage) found a 5-year survival rate of 48% for T1, 23% for T2, 5% for T3, and 5% for T4 disease. Pradhan reported slightly higher figures, although his endpoint was 18-month survival—approximately two thirds of the patients in his study presented with stage III or IV disease. Nodal status also adversely affects survival. Axon et al reported the highest 5-year survival rate (63%) in patients with negative cervical nodes who received surgery as primary treatment. However, other reports place rates as low as 20%. N1 disease survival rates ranged from 9-20%, and N2 or higher disease was always fatal.
The primary treatment modality also has a significant effect on overall survival. While evaluating 146 patients, Pradhan noted a 24% recurrence rate after surgery but found that 92% of patients treated with primary radiation had a recurrence. Stell et al and Axon et al came to a similar conclusion, although the disparity in 5-year survival rates between radiation (23%) and surgery (45%) was more modest.
In the United States, overall survival rates for postcricoid carcinoma were estimated best by a voluntary questionnaire developed by the Commission on Cancer's National Cancer Data Committee (reported by Hoffman et al in 1997). Postcricoid carcinoma contributed to only 2.4-3.1% of all cases of hypopharyngeal carcinoma. The 5-year disease-free survival rate, at 45.4%, was slightly better than rates for piriform sinus cancer. (Treatment methods were not noted.) Spector et al showed that surgery followed by postoperative radiation could achieve 5-year survival rates as high as 65%. In contrast, Gluckman showed a 40% survival for T1 and T2 lesions that initially were treated with surgery, while Clayman reported a 52% survival rate in early-stage hypopharyngeal cancer treated primarily with radiation.
As noted earlier and as evidenced from the above data, varying survival rates have been reported for this disease. Factors that influence these rates include the percentage of patients who have advanced disease, extent of submucosal spread, percentage of patients with regional and distant metastases, and treatment protocol. To evaluate the efficacy of surgery over radiation as primary treatment, remember that the volume of disease and the tumor response to chemotherapy have proved predictive of a good response to primary radiation, thus, in certain cases avoiding the morbidity of surgery.
Future and Controversies
Certainly, the most controversial subject surrounding treatment of postcricoid carcinoma is whether to initiate treatment with radiation or surgery. The desire to use radiation derives from morbidity associated with total laryngectomy with possible total pharyngectomy. With average 5-year survival rates hovering in the range of 25-40%, treating the cancer as aggressively as possible seems prudent, which means surgery followed by radiation.
The literature supports both premises. Reports from the United Kingdom and India show a survival advantage to surgery as the initial treatment, but their radiation doses are lower than modern standards (55 Gy vs 70 Gy). In contrast, several studies show equal cure rates using radiation therapy alone, absent cartilage invasion. While surgical salvage is successful only approximately 20% of the time, complications with this approach are not excessive.
The addition of chemotherapy to the treatment protocol improves cure rates by 2 mechanisms. If given in the neoadjuvant setting, chemotherapy selects tumors responsive to radiation therapy but apparently contributes no survival advantage itself. When given concomitantly with radiation, the different mechanism of cell death complements the effect of radiation and seems to improve overall survival, although earlier studies indicate no difference. A different chemotherapy delivery method calls for supradose intra-arterial cisplatin delivery with systemic neutralization using thiosulfate delivered once per week for 4 weeks during radiation treatment. While long-term data are still pending, impressive locoregional control rates (with average 18-mo follow-up) have been published.
The future of cancer treatment almost certainly includes some form of gene therapy. Numerous trials are evaluating different genes (eg, TP53, E1A, MHC class II), yet none has found significant advantage. This may be because these trials are approved for end-stage patients, and overall survival parameters are hard to improve. Other endpoints (eg, time to recurrence, slower tumor progression) are equally valid parameters, and significant improvement would justify widespread use of that gene. Other issues requiring clarification include delivery vehicles (eg, plasmid vs viral vector vs naked deoxyribonucleic acid), delivery methods, and timing of delivery.
Finally, immunomodulators will probably be used once underlying mechanisms are understood. Immunomodulators might include cancer vaccines (similar to breast cancer treatments using HER/neu), antibodies that block the epidermal growth factor receptor, or lymphocytes that target tumors. Steven Rosenberg, MD, PhD, at the National Institute of Health helped pioneer the coadministration of patients' own tumor-invading lymphocytes and various cytokine cocktails for patients with melanoma. Newer strategies use allogeneic immune systems to target cancer. So far, this approach has been used only in hematogenous cancers, but application to solid tumors is under investigation.
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Further Reading
Keywords
malignant tumors of the postcricoid area, hypopharyngeal carcinoma, hypopharynx cancer, hypopharyngeal cancer, hypopharynx cancer, head and neck cancer, head and neck carcinoma, postcricoid cancer, post-cricoid cancer, postcricoid carcinoma, post-cricoid carcinoma, hypopharyngeal tumor, hypopharynx tumor, hypopharyngeal malignancy, postcricoid malignancy, Plummer-Vinson syndrome, Paterson-Brown-Kelly syndrome, squamous cell carcinoma, SCC, head and neck squamous cell carcinoma, head and neck SCC
