Carcinoma In Situ (CIS) of the larynx is probably the earliest stage of squamous cancer, and basically means the cancer cannot be shown under the microscope to have started invading into the tissue beneath the surface. Studies following untreated symptomatic CIS of the vocal cords suggest that the natural history of this condition, once diagnosed, involves transformation to invasive disease in over 60% of cases.Management of glottic CIS is complicated not only by uncertainties in its diagnosis and prognosis, but also by an ongoing debate regarding the optimal treatment approach. Although radical surgery is now generally considered unnecessary, vocal cord stripping offers a simple, generally well-tolerated treatment strategy, although multiple procedures are often necessary  . Experience with laser excision is more limited, but this has also been recommended by some authors as a primary treatment approach . Radiation therapy, while the treatment of choice for early-stage invasive glottic cancer , is often reserved only for recurrence after surgical treatment of glottic CIS or for patients in whom follow-up may be unreliable.. Some authors, however, recommend RT as the primary treatment approach

The literature contains no reports of prospective studies comparing different treatment strategies. Due to the rarity of glottic CIS, many retrospective studies are limited by small numbers of patients; however, several recent reviews  have combined data from numerous published studies. These reports indicate the effectiveness of RT in achieving local control (80-84%), which is comparable to that for vocal cord stripping (60-66%), and laser therapy (68-92%). Some studies demonstrating the role of radiation are noted below:

Radiotherapy for carcinoma in situ of the true vocal cords.

Head Neck 2002 Apr;24(4):390-4 Garcia-Serra A; Hinerman RW; Amdur RJ; Morris CG; Mendenhall WM
Department of Radiation Oncology, University of Florida College of Medicine, PO Box 100385, Gainesville, Florida 32610-0385, USA.

To report long-term rates of tumor control after radiotherapy (RT) for carcinoma in situ (CIS) of the true vocal cords (TVC). Thirty patients with CIS of the TVC were treated between July 1967 and May 1998 with curative intent using megavoltage RT. Most patients (28 of 30) were treated with cobalt-60 through small (usually 5 x 5 cm) fields. Median RT dose was 56.25 Gy (range, 56.25-75 Gy; mean dose, 59.15 Gy) at 2.25 Gy per fraction. With a mean follow-up of 7.1 years (range, 2-17 years), the 5-year rates of local control, local control with larynx preservation, and ultimate local control (including salvage surgery) were the following: 88%, 88%, and 100%, respectively. Invasive squamous cell carcinoma developed in three (10%) of the patients. Time to failure was 14 months, 34 months, and 48 months, respectively. All three patients were surgically salvaged with a total laryngectomy. Cause-specific survival at 5 years was 100%. There were no late complications. CONCLUSIONS: RT to approximately 60 Gy at 2.25 Gy per fraction using small (5 x 5 cm) fields produces excellent results with CIS of the TVC.

Treatment results of carcinoma in situ of the glottis: an analysis of 82 cases.

Arch Otolaryngol Head Neck Surg 2000 Nov;126(11):1305-12 Le QT; Takamiya R; Shu HK; Smitt M; Singer M; Terris DJ; Fee WE; Goffinet DR; Fu KK
Department of Radiation Oncology, Stanford University Medical Center, 300 Pasteur Dr, Stanford, CA 94305-5302, USA. qle@reyes.stanford.edu.

Review of 82 cases treated definitively for glottic carcinoma in situ between 1958 and 1998. The median follow-up for all patients was 112 months, and 90% had more than 2 years of follow-up. SETTING: Academic tertiary care referral centers. INTERVENTION: Fifteen patients were treated with vocal cord stripping (group 1), 13 with more extensive surgery (group 2) including endoscopic laser resection (11 patients) and hemilaryngectomy (2 patients), and 54 with radiotherapy (group 3). Thirty patients had anterior commissure involvement and 9 had bilateral vocal cord involvement. Radiotherapy was delivered via opposed lateral fields at 1.5 to 2.4 Gy per fraction per day (median fraction size, 2 Gy), 5 days per week. The median total dose was 64 Gy, and the median overall time was 47 days. MAIN OUTCOME MEASURES: Initial locoregional control (LRC), ultimate LRC, and larynx preservation. RESULTS: The 10-year initial LRC rates were 56% for group 1, 71% for group 2, and 79% for group 3.  Anterior commissure involvement was an important prognostic factor for LRC on both univariate (P =.03) and multivariate (P =.04; hazard ratio, 1.6) analysis, and its influence appeared to be mainly confined to the surgically treated patients (groups 1 and 2). The 10-year larynx preservation rates were 92% for group 1, 70% for group 2, and 85% for group 3. Anterior commissure involvement was the only important prognostic factor for larynx preservation (P =. 01) on univariate analysis. All but 2 patients in whom treatment failed underwent successful salvage surgery. Voice quality was deemed good to excellent in 73% of the patients in group 1, 40% in group 2, and 68% in group 3. CONCLUSIONS: Treatment of carcinoma in situ of the glottis with vocal cord stripping or more extensive surgery or radiotherapy provided excellent ultimate LRC and comparable larynx preservation rates. Anterior commissure involvement was associated with poorer initial LRC and larynx preservation, particularly in the surgically treated patients. The choice of initial treatment should be individualized, depending on patient age, reliability, and tumor extent. Pretreatment and posttreatment objective evaluation of voice quality should be helpful in determining the best therapy for these patients

The role of radiotherapy in the management of carcinoma in situ of the glottic larynx.

Am J Clin Oncol 1998 Jun;21(3):298-301 Medini E; Medini I; Lee CK; Gapany M; Levitt SH
Department of Therapeutic Radiology, Veterans Administration Medical Center, Minneapolis, Minnesota 55417, USA.

Carcinoma in situ of the glottic larynx is a rare malignancy, comprising only 1% to 2% of laryngeal biopsy. The management of these lesions remains controversial. In this article, the authors present results and analysis of the management of 20 patients having these lesions treated by radiotherapy. A total of 20 patients who had carcinoma in situ of the glottis were treated with curative intent with radiotherapy at the Veterans Administration Medical Center, Minneapolis, Minnesota, U.S.A. from November 1972 through March 1993. Before radiotherapy , eight patients had only biopsies of the glottic larynx, five had one stripping procedure, and seven patients had two or three stripping procedures. Of the 20 patients, 19 are available for retrospective analysis, with a minimum follow-up of 4 years and a median follow-up of 7.3 years. Treatment was given to all patients by megavoltage units (cobalt 60, 2; 4-mV linear accelerator, 18). Patients were treated using bilateral opposed wedged 6-cm x 6-cm fields, with a dose of 1.75 Gy per fraction to a total median dose of 68.4 Gy in 40 fractions over 56 elapsed treatment days. The Kaplan-Meier method was used for survival analysis. The 4-year disease-free survival was 95% after irradiation. The actuarial disease-free survival for 5 and 10 years was 95%. Surgical salvage failed in one patient who had a laryngectomy for recurrent invasive squamous cell carcinoma at 34 months after radiotherapy. Two patients developed severe shortness of breath because of laryngeal edema, which required tracheostomy. Sixteen patients reported subjective significant improvement of their voice quality, and four reported no change. Radiotherapy is an excellent choice for patients who have recurrent carcinoma in situ after undergoing stripping procedures or for those patients who live too far from a medical facility to allow close follow-up and repetitive surgical procedures. These results are comparable to those of other investigators who used radiotherapy with higher dose per fraction..

Carcinoma-in-situ of the glottic larynx: results of treatment with radiation therapy.

Int J Radiat Oncol Biol Phys 2001 Apr 1;49(5):1235-8 Spayne JA; Warde P; O'Sullivan B; Payne D; Liu FF; Waldron J; Gullane PJ; Cummings BJ
Department of Radiation Oncology, Princess Margaret Hospital/University of Toronto, Toronto, Ontario, Canada.

Carcinoma-in-situ (CIS) of the vocal cords frequently progresses to invasive disease if untreated. Treatment approaches include vocal cord stripping, radiation therapy (RT), and laser excision. The purpose of this analysis was to assess the efficacy and safety of a standard RT regimen in the treatment of this condition. METHODS AND MATERIALS: Between January 1980 and December 1994, 67 patients (52 men, 15 women; median age, 65 years) with glottic CIS were treated with RT. The standard RT regimen was 51 Gy in 20 fractions given over 4 weeks (99% of patients). Prior to receiving RT, 21 patients (31%) had undergone 1 or 2 vocal cord stripping procedures, and 1 had been treated with laser. RESULTS: With a median follow-up of 6.5 years, 1 patient developed invasive glottic cancer, giving a 5-year actuarial local control rate of 98%. This patient recurred 14 months after treatment and was salvaged with laryngectomy. He is currently free of disease 2 years after surgery. There were no serious acute or late treatment complications. Sixteen patients (24%) developed subsequent malignancies, 8 of these being in the upper aerodigestive tract, although none were in the radiation field. CONCLUSIONS: Moderate-dose radiation therapy is an effective treatment for glottic CIS. It is well tolerated, produces no serious acute or long-term side effects, with an excellent cure rate.