Surgical Approach to Organ Preservation in the Treatment of Cancer of the Larynx

The article by Dr. Weinstein is adiscussion of the newer surgicaloptions available for the treatment of patients with laryngeal cancer. Severalaspects of the article deserve mention.

One positive aspect is that it reviews alternative treatmentsfor laryngeal cancer. However, several misconceptions are presented that warrantdiscussion. The first misconception is the title of the article, "SurgicalApproach to Organ Preservation in the Treatment of Cancer of the Larynx." Amore accurate title would refer to limited resection or function-preservingsurgery in the treatment of patients with laryngeal cancer. Is removal of"both true and false cords as well as the entire epiglottis and thyroidcartilage," as performed in a supracricoid partial laryngectomy withcricohyoidopexy, truly organ/function preservation?

The belief that the larynx is a "tone generator" canlead to a potential misinterpretation of quality-of-life studies. The authorstates, "Studies of voice quality after supracricoid partial laryngectomywith cricohyoidepiglottopexy have shown that, at 6 months, the phrase groupingand number or words per minute are similar to that of normal speakers, while thefundamental frequency is lower and wider than normal, suggesting voiceinstability."[1] The significance of the voice instability is unclear.

Furthermore, the author states that the quality of speech afterthis procedure is superior to that of total laryngectomy patients. This is not afair comparison—the comparison should be to nonsurgical organ-preservingprocedures. The question once again arises, if the true function of the organ isnot being preserved, is this truly an organ-preserving procedure?

Other Quality-of-Life Issues

Although the author mentions that "it is the stoma and notthe posttreatment voice quality that is the major determinant of quality oflife,"[2] there are other determining factors derived from surveys andquestionnaires. Patients treated with surgery tend to have a lower quality oflife, compared to patients treated with radiation with or without chemotherapy.For example, long-term follow-up from the Veterans Affairs (VA) Laryngeal CancerStudy Group demonstrated a better quality of life in patients randomized tochemotherapy plus radiation vs surgery plus radiation.[3] In anotherquality-of-life study of head and neck cancers, laryngectomy patients had lowerquality-of-life scores than patients treated with radiation alone.[4]

Although there are limited data on the quality of life ofpatients with early-stage lesions, voice quality appears to be better amongpatients treated nonsurgically. In a study by Vordonck-de Leeuw, voice qualityfollowing radiation therapy became comparable to the vocal performance ofcontrol speakers in 50% of patients. Also, voice quality was worse for patientswho underwent vocal cord stripping for initial diagnosis instead of biopsies.[5]There is also evidence that voice quality for early laryngeal lesions is betterwith radiation therapy than with laser excision.[6,7] In other studies, however,as mentioned in the article, voice quality is equivalent. Thus, although thereare alternative options for the treatment of early-stage lesions, there is ampleevidence to show that radiation alone produces excellent results in early-stagecancers of the larynx, with minimal side effects.

Misrepresentation of Issues

Another deficiency in this article is a lack of balance andaccurate reporting of results. Throughout the article, the author reportsselected results on selected patients. For example, in the section entitled"Supracricoid Partial Laryngectomy With Cricohyoidepiglottopexy," theauthor states, "Among 67 patients with T2 lesions… the5-year local control rate was 95.5%,"[8] and "[i]n 20 patients with T3glottic carcinoma with vocal cord fixation, the 5-year actuarial local controlrate was 90%."[9] However, the author fails to mention that both of thesetrials used induction chemotherapy. This is an important omission since we knowthat the use of induction chemotherapy changes the outcome of the disease, asseen in the VA laryngeal cancer study.[10]

The authors also fail to mentionthe use of radiation therapy in manyof the trials. In the section "Supraglottic Partial Laryngectomy," theauthors cite five references regarding the outcome of this procedure. However,three of these five series use radiation therapy in a significant number oftheir patients. In Lee et al, 83% of patients received postoperative radiationtherapy[11]; in Spaulding et al, all patients received either pre- orpostoperative radiation therapy[12]; and in Herranz-Gonzalez et al,postoperative radiation therapy was administered to node-positive patients.[13]

This important information was not presented in an article onorgan preservation, although we know that the addition of radiation to surgerywill compromise organ function.[14] Therefore, the question that remainsunanswered is: What is the true local control rate for these procedures as asingle modality?

Surgical Expertise

One of the difficulties with the surgeries mentioned in thisarticle is that they require a high degree of surgical skill. These proceduresare complex and demand significant expertise and experience. The author states,"A resident or fellow in surgical training might have been exposed to few,if any, extended vertical partial laryngectomies and extended supraglotticpartial laryngectomies in training, making it difficult to use these proceduresin practice." By the same reasoning, physicians-in-training will havelittle opportunity to master the techniques mentioned in this article, makingthese procedures impractical and not widely applicable. The fact that most ofthe references are from single institutions raises similar concerns.

Thus, except for select medical centers with select surgeons,these surgeries will have limited use. Furthermore, only select patients aresuitable for these procedures. A majority of patients mentioned in thereferenced studies were node negative,[8,9,15-18] and all patients need to becarefully selected for the appropriate procedure.

Lack of Outcome Data

Another criticism of the article is the occasional lack ofoutcome data. In the section on endoscopic approaches for organ-preservingsurgery of carcinomas arising at the glottic level, the author provides minimaldata on outcome. He states, "A reasonable approach is to recommendendoscopic excision when the surgeon predicts that the voice outcome will becomparable with radiation therapy." But he does not cite a single referenceregarding local control or outcome associated with the use of endoscopicexcision.

Thomas reported a 23% (24/106) retreatment rate for localrecurrences or new primary lesions for early T1 glottic cancers treated withendoscopic procedures,[19] and Moreau had no local failures in 160 patientstreated with endoscopic cordectomies.[20] This suggests that there is a highdegree of technique variation and patient selection in these procedures.

Unequivalent Comparisons

A final aspect that deserves comment is that the articlecompares modern surgical approaches with older nonsurgical approaches. Forexample, there is evidence that hyperfractioned radiation therapy produces abetter outcome than standard fractionation. In a randomized study by theRadiation Therapy Oncology Group (RTOG), hyperfractionation and acceleratedfractionation radiation therapy with a concomitant boost were more effectivethan standard fractionation for locally advanced head and neck cancer.[21] Also,although the main comparison of surgery vs nonsurgical approaches is based onthe VA laryngeal cancer study (which used sequential chemotherapy andradiotherapy), recent evidence suggests that concomitant chemotherapy andradiotherapy may be more effective in organ preservation.

Several phase II studies have demonstrated excellent results foradvanced head and neck cancer with concomitant chemotherapy and radiationtherapy.[22-25] There is also a phase III study that demonstrated improved3-year disease-free and overall survival with concomitant chemotherapy andradiation therapy vs radiation therapy alone in advanced-stage oropharyngealcancers.[26] Furthermore, the addition of hyperfractionated radiation withconcomitant radiation therapy is associated with improved 5-year locoregionalcontrol and relapse-free survival rates, compared to hyperfractionated radiationtherapy alone in advanced head and neck cancers.[27] Therefore, the optimalnonsurgical organ-preservation technique is yet to be determined.

Only a randomized trial in specific subsets of head and neckcancer—ie, early laryngeal or advanced T3 laryngeal cancer—will provideevidence as to which treatments are superior for organ preservation, function,and survival.

References:

1. Crevier-Buchman L, Laccourreye O, Weinstein G, et al:Evolution of speech and voice following supracricoid partial laryngectomy. JLaryngol Otol 109:410-413, 1995.

2. DeSanto L, Olson K, Perry W: Quality of life after surgicaltreatment of cancer of the larynx. Ann Otol Rhinol Laryngol 104:763-769, 1995.

3. Terrell JE, Fisher SG, Wolf GT: Long-term quality of lifeafter treatment of laryngeal cancer. The Veterans Affairs Laryngeal Cancer StudyGroup. Arch Otolaryngol Head Neck Surg 124(9):964-971, 1998.

4. Campbell BH, Marbella A, Layde PM: Quality of life andrecurrence concern in survivor of head and neck cancer. Laryngoscope110(6):895-906, 2000.

5. Vordonck-de Leeuw IM, Keuss RB, Hilgers FJ, et al:Consequences of voice impairment in daily life following radiotherapy for earlyglottic cancer: Voice quality, vocal function, and vocal performance. Int JRadiat Oncol Biol Phys 44(5):1071-1078, 1999.

6. Rydell R, Schalen L, Fey S, et al: Voice evaluation beforeand after laser excision vs radiotherapy of T1A glottic carcinoma. ActaOtolaryngol 115(4):560-565, 1995.

7. Epstein BE, Lee DJ, Kashima H, et al: Stage T1 glotticcarcinoma: results of radiation therapy or laser excision. Radiology175(2):567-570, 1990.

8. Laccourreye O, Weinstein G, Brasnu D, et al: A clinical trialof continuous cisplatin-fluorouracil induction chemotherapy and supracricoidpartial laryngectomy for glottic carcinoma classified as T2 [see comments].Cancer 74:2781-2790, 1994.

9. Laccourreye O, Salzer SJ, Brasnu, et al: Glottic carcinomawith a fixed true vocal cord: Outcomes after neoadjuvant chemotherapy andsupracricoid partial laryngectomy with cricohyoidoepiglottopexy. OtolaryngolHead Neck Surg 114:400-406, 1996.

10. Induction chemotherapy plus radiation compared with surgeryplus radiation in patients with advanced laryngeal cancer. The Department ofVeterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324:1685-1690, 1991.

11. Lee NK, Goepfert H, Wendt CD: Supraglottic laryngectomy forintermediate-stage cancer: U. T. M .D. Anderson Cancer Center experience withcombined therapy. Laryngoscope 100:831-836, 1990.

12. Spaulding CA, Constable WC, Levine PA, et al: Partiallaryngectomy and radiotherapy for supraglottic cancer: A conservative approach.Ann Otol Rhinol Laryngol 98:125-129, 1989.

13. Herranz-Gonzalez J, Gavilan J, Martinez-Vidal J, et al:Supraglottic laryngectomy: Functional and oncological results. Ann Otol RhinolLaryngol 105:18-22, 1996.

14. Spriano G, Antognoni P, Sanguineti G, et al: Laryngeallong-term morbidity after supraglottic laryngectomy and postoperative radiationtherapy. Am J Otolaryngol 21(1):14-21, 2000

15. Laccourreye H, Laccourreye O, Weinstein G, et al:Supracricoid laryngectomy with cricohyoidopexy: A partial laryngeal procedurefor selected supraglottic and transglottic carcinomas. Laryngoscope 100:735-741,1990.

16. Laccourreye H, Laccourreye O, Weinstein G, et al:Supracricoid laryngectomy with cricohyoidoepiglottopexy: A partial laryngealprocedure of glottic carcinoma. Ann Otol Rhinol Laryngol 99:421-426, 1990.

17. Bron L, Brossard E, Monnier P, et al: Supracricoid partiallaryngectomy with cricohyoidoepiglottopexy and cricohyoidopexy for glottic andsupraglottic carcinomas. Laryngoscope 110:627-634, 2000.

18. de Vincentiis M, Minni A, Gallo A, et al: Supracricoidpartial laryngectomies: Oncologic and functional results. Head Neck 20:504-509,1998.

19. Thomas JV, Olsen KD, Neel HB, et al: Recurrences afterendoscopic management of early (T1) glottic carcinoma. Laryngoscope104(9):1099-1104, 1994.

20. Moreau PR: Treatment of laryngeal carcinomas afterendoscopic microsurgery. Laryngoscope 110(6):1000-1006, 2000.

21. Fu KK, Pajak TF, Trotti A, et al: A Radiation TherapyOncology Group (RTOG) phase III randomized study to compare hyperfractionationand two variants of accelerated fractionation radiotherapy for head and necksquamous cell carcinomas: First report of RTOG 9003 [see comments]. Int J RadiatOncol Biol Phys 48(1):7-16, 2000.

22. Vokes EE, Kies MS, Haraf DJ, et al: Concomitantchemoradiotherapy as primary therapy for locoregionally advanced head and neckcancer. J Clin Oncol 18 (8):1652-1661, 2000.

23. Vokes EE, Haraf DJ, Brockstein BE, et al: Paclitaxel,5-fluorouracil, hydroxyurea, and concomitant radiation therapy forpoor-prognosis head and neck cancer. Semin Radiat Oncol 9(2 suppl 1):70-76,1999.

24. Haraf DJ, Kies M, Rademaker AW, et al: Radiation therapywith concomitant hydroxurea and fluorouracil in stage II and III head and neckcancer. J Clin Oncol 17(2):638-644, 1999.

25. Bensadoun RJ, Etienne MC, Dassonville O, et al: Concomitantb.i.d. radiotherapy and chemotherapy with cisplatin and 5-fluorouracil inunresectable squamous-cell carcinoma of the pharynx. Int J Radiat Oncol BiolPhys 42(2):237-245, 1998.

26. Calais G, Alfonsi M, Bardet E, et al: Randomized trial ofradiation therapy vs concomitant chemotherapy and radiation therapy foradvanced-stage oropharynx carcinoma [see comments]. J Natl Cancer Inst91(24):2081-2086, 1999.

27. Brizel DM, Albers ME, Fisher SR, et al: Hyperfractionatedirradiation with or without concurrent chemotherapy for locally advanced headand neck cancer [see comments]. N Engl J Med 338(25):1798-1804, 1998.