Transoral laser microsurgery in treatment of pt2 and pt3 glottic laryngeal squamous cell carcinoma results of 391 patients

Transcription

1 ORIGINAL ARTICLE Transoral laser microsurgery in treatment of pt2 and pt3 glottic laryngeal squamous cell carcinoma results of 391 patients Martin Canis, 1* Alexios Martin, 2 Friedrich Ihler, 1 Hendrik A. Wolff, 3 Martina Kron, 4 Christoph Matthias, 1 Wolfgang Steiner 1 1 Department of Otorhinolaryngology, Head and Neck Surgery, University of G ottingen, Germany, 2 Department of Audiology and Phoniatrics, University of Berlin, Germany, 3 Department of Radiation Oncology, University of G ottingen, Germany, 4 Institute of Epidemiology and Medical Biometry, University of Ulm, Germany. Accepted 15 May 2013 Published online 29 May 2013 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. The purpose of this study was to evaluate oncological and functional results of transoral laser microsurgery (TLM) in patients with T2 and T3 glottic laryngeal squamous cell carcinoma (SCC). Methods. A retrospective chart analysis was carried out. Cases were classified into categories pt2a, pt2b, and pt3. Treatment was exclusively TLM 6 selective neck dissection and adjuvant (chemo)radiotherapy. Results. Three hundred ninety-one patients were treated by TLM; 142 cases were category pt2a, 127 were pt2b, and 122 were pt3. Median follow-up was 71 months. Five-year overall, recurrence-free, and disease specific survival rates were 72.2%, 76.4%, and 93.2% for pt2a tumors, 64.9%, 57.3%, and 83.9% for pt2b tumors, and 58.6%, 57.8%, and 84.1% for pt3 tumors, respectively. Larynx preservation was achieved in 93% (pt2a) and 83% (pt2b and pt3). Conclusion. Results are comparable to open partial or total laryngectomy and superior to primary (chemo)radiotherapy. TLM results in a lower morbidity and superior function compared to standard treatment. VC 2013 Wiley Periodicals, Inc. Head Neck 36: , 2014 KEY WORDS: T2-3 glottic laryngeal carcinoma, larynx, transoral laser microsurgery, oncologic and functional outcomes, organ preservation INTRODUCTION Since the introduction of transoral laser microsurgery (TLM) for the treatment of early glottic cancer by Jako and Strong 1 in 1972, indications for its use have been vastly expanded. Initially the technique was only used for the palliative reduction of airway obstructing laryngeal carcinomas and the treatment of early glottic cancer. Since the early 1980s, Steiner et al 2 5 expanded the indications to all tumor categories of the upper aerodigestive tract (ADT). However, open partial resection, total laryngectomy, and primary chemoradiotherapy are the accepted standard treatment modalities for early (T2a) and advanced (T2b, T3) glottic cancers in many countries. The use of TLM is widely accepted currently for early T1 and T2a glottic disease because its use has distinct advantages over both the open approaches and primary chemoradiotherapy, including organ and function preservation, faster recovery of swallowing function, lower incidences of aspiration pneumonia and fistulae, avoidance of tracheotomy, and shorter period of hospitalization. Since 1986, a prospective database has been maintained of all patients undergoing TLM at the University of G ottingen Medical Centre. The purpose of this study was to investigate the *Corresponding author: M. Canis, Department of Otorhinolaryngology, Head and Neck Surgery, University of G ottingen, G ottingen, Germany. martin.canis@med.uni-goettingen.de Martin Canis and Alexios Martin contributed equally to this work. results of TLM in combination with selective neck dissection, with or without adjuvant chemoradiotherapy, and to describe it as a therapeutic option in the treatment of T2a/T2b and T3 glottic laryngeal carcinoma. The second purpose was to compare our data to the results obtained by open partial or total laryngectomy and by primary radiotherapy alone, or in combination with induction or synchronous chemotherapy published in literature. PATIENTS AND METHODS Between August 1979 and December 2006, a total of 391 previously untreated patients with glottic laryngeal squamous cell carcinoma (SCC; T2 3, N0 2, M0) were treated with curative intent at the Departments for Otorhinolaryngology Head and Neck Surgery of the University of Erlangen ( , surgery by the senior author, n 5 83) and G ottingen (August 1986 December 2006, surgery by 7 surgeons, n 5 308). Previously untreated tumors were staged according to the current classification of the Union Internationale Contre le Cancer and the American Joint Committee on Cancer. 6 Exclusion criteria for this study were non-scc tumors, patients with simultaneous second primaries or distant metastases, and N3 neck disease. Of 532 patients with a T2/T3 laryngeal cancer presenting themselves for treatment in our hospital, 141 had to be excluded, 90% men and 10% women. The reasons were open partial laryngectomy in 7 patients, total laryngectomy in 8 patients, and palliative treatment intention HEAD & NECK DOI /HED JUNE

2 CANIS ET AL. in 5 patients. Eighty patients were diagnosed with recurrent or residual disease after primary treatment elsewhere. Previous treatment for cancer in the upper ADT (19 patients) or simultaneous second primaries (9 patients) led to the exclusion of 28 patients. The remaining 13 patients were excluded because of N3 neck disease, non- SCC histology, simultaneous distant metastases, or death before therapy. A total of 391 patients fulfilled the inclusion criteria, 353 were men (90%) and 38 were women (10%). The median age was 61 years, with a range from 16 to 87 years. All patients were followed at least for 24 months, the median follow-up period being 71 months. Mean follow-up for pt2a, pt2b, and pt3 tumors was months, months, and months. Of these patients, 142 belonged to the tumor category pt2a, 127 to pt2b, and 122 to pt3. All surgical procedures were performed exclusively by transoral approach. In addition to transoral microsurgical laser excision of the primary tumor, selective neck dissection and/or adjuvant chemoradiotherapy was performed, depending on the extent of laryngeal and neck disease. Preoperative examination Pretherapeutic examination comprised routinely a magnifying rigid or flexible endoscopic examination, followed by ultrasonographic examination of the neck. CT or MRI of the neck was not undertaken routinely. Further standard preoperative investigations included x-ray examination of the chest and ultrasonography of the abdomen. Panendoscopy was performed with the patient under general anesthesia at the beginning of the surgical procedure for laser biopsy if the carcinoma was not yet proven by histology and with the intention to exclude any second primary tumor in the ADT and upper digestive tract. Operative technique The surgical procedures were performed with the patients under general anesthesia and with orotracheal intubation. In most cases, a closed laryngoscope was used for exposure of the glottic tumor. When appropriate, laryngoscopes with a smaller diameter were used. This was necessary when exposure of the anterior commissure or subglottis appeared difficult because of anatomic reasons. Depending on the localization and size of the tumor, the endotracheal tube was placed above the upper blade of the laryngoscope in order to expose the posterior commissure. As good exposure and visualization are prerequisites of a safe and successful resection, the laryngoscope had to be repositioned several times during operations of larger tumors. In order to remove laser plume, which can reduce visibility substantially, the laryngoscopes (Karl Storz, Tuttlingen, Germany) were equipped with integrated suction tubes. More extended tumors were excised by segmental resection in several portions. This unconventional technique with cutting through the tumor does not compromise the oncological excision because lymphatic vessels at the wound margins are sealed immediately, as shown by Werner et al. 7 In contrast to classic en bloc resection, the tumor then was resected in a step-by-step procedure under microscopic magnification by using a CO 2 laser in continuous superpulse mode. 2,8 Using this technique, the surgeon accurately follows and removes the tumor under high magnification, while preserving as much healthy and functionally important tissue as possible. Tissue structure and cutting characteristics of the CO 2 laser allow the surgeon to differentiate between healthy tissue and tumor; therefore, frozen section biopsies were not performed on a regular basis for laryngeal carcinoma. Tumors were resected under the microscope with surgical resection margins in healthy tissue of at least several millimeters. For T2a and well-confined T2b lesions, a safe margin can be 2 to 3 millimeters, thus preserving the maximal amount of functionally important tissue. However, for larger T3 tumors and those with less borders less clearly identifiable, a margin of 5 mm of healthy tissue may be required. As the quality of postoperative voice depends directly on the extent of the resection, it was our goal to preserve as much healthy laryngeal tissue as possible. This means that, in some cases, a second resection was warranted when unclear margins were discussed with the pathologist. Tumors that extended to the paraglottic space required a resection that reaches laterally to the thyroid cartilage and caudally to the cricoid cartilage. In more advanced tumors, the resection was extended to the perichondrium of the thyroid and cricoid cartilage, the arytenoid cartilage and/or the thyroid cartilage, and the extralaryngeal tissue. We used a laser system (40c, Lumenis, Dreieich, Germany) to perform the surgical procedures. The laser system was equipped with a micromanipulator attached to the operating microscope (OPMI Vario/S88, Zeiss, G ottingen, Germany). The focus diameter of the micromanipulator was 0.5 mm and 0.25 mm, approximating to 2080 to 3900 W/cm 2 of laser energy, respectively. The level of laser power used varied from 3W for subtle resections to 15W when cutting through large tumor masses. This administered laser power was able to coagulate vessels with a maximum diameter of 0.3 to 0.5. When larger vessels of the superior laryngeal vasculature were opened during surgery, vessels were clearly defined and double clipped. If large parts of the thyroid cartilage were exposed or partially removed during resection of the tumor, we administered penicillin or clindamycin perioperatively in order to avoid possible perichondritis. Treatment of primary tumor and neck One hundred twenty-eight of 142 patients (90%) with a pt2a tumor were treated exclusively by TLM. Additionally, 13 patients received a selective neck dissection, 10 patients a unilateral neck dissection, and 3 patients a bilateral neck dissection to the primary tumor site. Of the 127 pt2b tumors, 96 (76%) were treated by laser surgery alone. Additionally, 20 patients (16%) received a selective neck dissection, 16 patients underwent a unilateral neck dissection, and 4 patients had a bilateral neck dissection. Fifty-eight of 122 patients (48%) with a pt3 tumor received laser surgery only. Additionally, 60 of HEAD & NECK DOI /HED JUNE 2014

3 TRANSORAL LASER MICROSURGERY FOR PT2/PT3 GLOTTIC LARYNGEAL SCC FIGURE 1. Ten-year Kaplan Meier estimates for local control. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] patients (49%) received a selective neck dissection (47 unilateral, 13 bilateral). Postoperatively, 16 patients showed positive lymph node metastases: in patients with pt2a disease, 3 had pn1 metastases, in patients with pt2b disease, 2 had pn1 metastases, and in patients with pt3, 6 had pn1, and 5 patients with pn2b metastases were found. Adjuvant (chemo)radiotherapy Adjuvant (chemo)radiotherapy was mainly performed in cases of pn2 neck disease or when the histopathological examination revealed extracapsular spread and/or lymphangiosis carcinomatosa. In total, 25 patients received radiation, and concomitant chemotherapy was given in 13 cases. None of the patients with pt2a tumors received adjuvant radiotherapy, whereas 12 patients with pt2b and 13 patients with pt3 were irradiated postoperatively. Of all 391 patients in this study, only 7% were treated by adjuvant radiotherapy. Statistical methods All survival rates were calculated by using the Kaplan Meier method. The assessed endpoints were overall survival, recurrence-free survival, disease specific survival, local and loco-regional control, distant metastases, and second primaries. Overall survival was calculated on deaths from all possible causes, disease-specific survival was calculated on deaths from glottic cancer. For calculating recurrence-free survival, intercurrent deaths, and deaths because of secondary primary tumors, as well as patients alive without recurrences, were regarded as censored observations. Events included local and regional recurrences, distant, recurrent and late metastases, and deaths because of disease. For the calculation of local control rate, only local recurrences were considered as events whereas patients alive without local recurrence or death, regardless of reason, were counted as censored observations. The definition of local recurrence included carcinoma in situ as well as carcinoma occurring after completion of primary treatment. Survival times were calculated from the day of surgery to the date of occurrence of an event or the date of the last follow-up. RESULTS Local and locoregional control Figure 1 shows 5-year local control rate after endoscopic laser surgery for all patients related to T classification. Of pt2a tumors (n 5 142), local or locoregional recurrence was observed in 30 patients (21%), whereas pt2b tumors (n 5 127) showed local or locoregional recurrence in 44 cases (35%, and 39 of 122 patients (32%) with T3 tumors. Thus, in 113 patients (29%), local or locoregional recurrence occurred within the first 5 years. Table 1 gives patterns of TNM-related treatment failures after initial therapy. pt categories of the first local and locoregional recurrence of 113 patients are given in Table 2. Second primary tumors Twenty-three (16%) second primary tumors presented subsequently in the group with pt2a tumors, 3 of them in the head and neck region. Patients with pt2b lesions developed 18 (14%) second primaries, again, 2 of them were located in the head and neck region. Eighteen patients (15%) with pt3 tumors developed second primaries, with 3 of them located in the head and neck region. HEAD & NECK DOI /HED JUNE

4 CANIS ET AL. TABLE 1. First failures after initial therapy depending on T classification. pt No. of patients Local recurrence, No. of patients (%) Locoregional recurrence, No. of patients (%) Late metastasis, No. of patients (%) Recurrent metastasis, No. of patients (%) Total 2a (19) 3 (2) 6 (4) b (28) 8 (6) 5 (4) (26) 7 (6) 8 (7) 1 (1) 48 Total (24) 18 (5) 19 (5) 1 (0.3) 133 These second primary tumors were as follows, lung (n 5 16), gastrointestinal tract (n 5 18), urogenital system (n 5 8), and others (n 5 9). Second primary tumors were diagnosed between 0.6 and months (SD 50.5 months, mean 56.2 months). Survival 5-year recurrence-free survival rate (Kaplan Meier method) was 76.4% for pt2a tumors, 57.3% for pt2b, and 57.8% for pt3 (Figure 2). 5-year overall survival rate was 72.2%, 64.9%, and 58.6%, respectively (Figure 3). Disease-specific survival was measured as 93.2% for pt2a tumors, 83.9% for pt2b, and 84.1% for pt3 (Figure 4). Nine of the patients (6%) with pt2a tumors died of TNM-related causes, 39 patients (27%) from intercurrent diseases, and 13 patients (9%) from second primary tumors. Of the patients presenting with pt2b tumors, 21 (17%) died of TNM-related causes, 34 patients (27%) from intercurrent diseases, and 8 patients (6%) from second primary tumors, whereas 21 patients (17%) with pt3 tumors died of TNM-related causes, 29 patients (24%) from intercurrent diseases, and 11 patients (9%) from second primary tumors. Salvage therapy Salvage therapy (Table 3) after the first failure of primary therapy (n 5 133; 34.0%) consisted of laser microsurgery (n 5 52; 39.1%), laser microsurgery and neck dissection (n 5 5; 3.5%), laser microsurgery in combination with neck dissection and chemoradiotherapy (n 5 4; 3.0%), and laser microsurgery and (chemo)radiotherapy (n 5 6; 4.5%). Open partial resection was performed in 7 cases (5.3%), and total laryngectomy after the first failure was necessary in 30 cases (22.6%). After TLM with or without chemoradiotherapy, the larynx was preserved in 132 of the patients (93%) with pt2a, 106 of the patients (83%) with pt2b, and 101 of the patients (83%) with pt3. Postoperative complications The rate of postoperative complications was very low. We observed 3 cases of postoperative bleeding (1 case in each of the 3 tumor categories) that required revision microlaryngoscopy with coagulation and/or clipping in the operating room. One patient developed a cervical hematoma after neck dissection and had to be managed in the operating room. No patient needed tracheotomy intraoperatively; however, 1 patient with pt2a, 1 patient with pt2b, and 5 patients with pt3 needed temporary tracheotomy postoperatively. No patient had a persistent tracheotomy. One patient acquired therapy-related pneumonia because of aspiration, which was treated by antibiotics. No patient died because of bleeding, aspiration, and/or airway compromise. One patient developed glottic stenosis (pt3) that was treated successfully, 2 patients required microlaryngoscopy for laryngeal edema (pt3), and 4 patients developed postoperative cervical emphysema (T2b n 5 2; T3 n 5 2), which could be managed in a conservative way. Three patients (T2b n 5 2; T3 n 5 1) presented with perichondritis of the laryngeal cartilage, which were treated with antibiotics. Functional results One hundred forty-one patients (99%) with pt2a lesions, 118 patients (93%) with pt2b tumors, and 69 patients (57%) with pt3 lesions did not require a nasogastric feeding tube at any time. The remaining 63 patients (43%) with pt3 tumors required a feeding tube for 1 to 30 days. One patient with a pt2a tumor who had a history of ischemic stroke of the middle cerebral media required a percutaneous endoscopic gastrostomy (PEG) tube for several months. Among the patients with pt2b, no temporary PEG was needed, within the pt3 group, 3 temporary TABLE 2. rpt categories of all 113 first local and locoregional recurrences regarding initial T classifications. rpt No. of patients % pt2a (n 5 142) Totals pt2b (n 5 127) Totals pt3 (n 5 122) Totals HEAD & NECK DOI /HED JUNE 2014

5 TRANSORAL LASER MICROSURGERY FOR PT2/PT3 GLOTTIC LARYNGEAL SCC FIGURE 2. Ten-year Kaplan Meier estimates for overall survival. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] PEG tubes were necessary. In all groups, there were no permanent PEG tubes necessary and no laryngectomy because of functional problems that had to be performed. DISCUSSION Carcinomas of the pt2 category are a very heterogenous tumor entity. They comprise of tumors without impaired vocal fold mobility (T2a), which spread to the supraglottic and/or subglottic space, as well as vocal fold tumors with impaired mobility (T2b). These 2 entities differ considerably regarding the prognosis of the disease. Tumors with impaired mobility (T2b) are biologically and prognostically much more comparable to tumors with fixation of the vocal fold (T3). This is in line with the present data in which no significant differences were observable between pt2b and pt3 tumors. It is therefore FIGURE 3. Ten-year Kaplan Meier estimates for recurrence-free survival. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] HEAD & NECK DOI /HED JUNE

6 CANIS ET AL. FIGURE 4. Ten-year Kaplan Meier estimates for disease-specific survival. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] our opinion that a differentiation between T2a and T2b tumors is necessary. According to Holsinger and Diaz, 9 glottic cancers with impaired mobility should be classified together with cancers with fixation as T3 tumors (T3a/T3b). Standard treatment of T2/T3 glottic laryngeal carcinomas consists of open partial resection, total laryngectomy, or primary chemoradiotherapy. For pt2 carcinomas, local control rates of 52.76% have been achieved with vertical partial laryngectomy. 10,11 For T3 glottic carcinomas with vocal fold fixation, total laryngectomy (with or without adjuvant radiotherapy) is the standard surgical procedure. Locoregional control and 5-year overall survival is reported as 69% to 87% and 53% to 56%, respectively In selected cases, hemilaryngectomy is performed as an alternative to total laryngectomy in T3 cases. For partial laryngectomy, local control rates between 73% and 83% have been published Another surgical option when treating T2 and selected T3 cases is the supracricoid partial laryngectomy with cricohyoidoepiglottopexy (SCPL-CHEP), as described by Piquet et al, 17 and Chevalier et al, 19 and Piquet and Chevalier. 20 Chevalier et al 19 investigated 112 patients with glottic carcinoma and impaired mobility of the vocal fold (n 5 90) or vocal fold fixation (n 5 22). The authors observed a local control rate of 97.3% and a 5- year rate of larynx preservation of 95.5%. Contraindications for this procedure are fixation of the arytenoid cartilage, tumor spread to the upper border of the cricoid cartilage, infiltration of the cricoid or thyroid cartilage, extensive infiltration of the pre-epiglottic space, and extralaryngeal spread. 21 In contrast, these conditions are no contraindications for TLM. Notwithstanding, the oncological results with total laryngectomy or SCPL- CHEP are at least comparable or sometimes even better than those of TLM. SCPL-CHEP has also be undertaken in combination with neoadjuvant cisplatin and 5-fluorouracil chemotherapy Lacourreye et al 23 reported about 100 patients with T2 glottic laryngeal carcinoma who were treated by 3 cycles of neoadjuvant chemotherapy with intervals of 10 to 15 days and SCPL-CHEP. Preoperative vocal fold mobility was impaired in 54%, the anterior commissure was involved in 42%, and there was infraglottic involvement in 10% of the cases. Complete remission was achieved in 25% of patients and partial remission in 58%. Five-year local control rates of 97.7% for pt2a and 93.8% for pt2b cancers are reported with 95% of the patients retaining the larynx. The functional results were significantly worse than in our own study, with 9% of the patients having pneumonia because of postoperative aspiration and 1 functional total laryngectomy. Using the TABLE 3. Salvage therapy after the first failure for all 133 patients. Modality No. of patients % Laser alone Laser 1 neck dissection Laser 1 neck dissection 1 radiochemotherapy Laser 1 radiochemotherapy Open resection Total laryngectomy Neck dissection alone Neck dissection 1 radiochemotherapy Radiochemotherapy alone Other/unknown/no therapy Totals HEAD & NECK DOI /HED JUNE 2014

7 TRANSORAL LASER MICROSURGERY FOR PT2/PT3 GLOTTIC LARYNGEAL SCC same treatment regimen, Lacourreye et al 24 achieved a 3- year local control rate of 89.2% and a larynx preservation rate of 90% for patients with T3 glottic laryngeal carcinoma and fixation of the vocal fold. When compared to open partial surgery and to transoral laser surgery, the oncological outcomes of primary radiotherapy are worse than in both surgical procedures. Fiveyear local control rates for T2 carcinomas with mobile vocal folds are stated as low as 64% to 87% and the 5-year organ preservation is 75% to 87% The main problem with primary radiotherapy is the fact that a salvage laryngectomy has to be performed in most cases of recurrent disease. Further irradiation treatment is usually not an option. Local control after primary radiotherapy can be achieved in 60% to 76% of T2b cases, and organ preservation is stated in the literature as being between 70% and 80%. 25,27,28,30 32 When treating T3 tumors, these rates are even lower: 5-year overall survival is stated as 51% to 59%, and organ preservation 50% to 76%. 31,33,34 In a large review of the National Cancer Data Base, Hoffman et al 35 investigated data of 158,426 patients with laryngeal cancer. The authors found that survival had decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this time, there has been an increase in the nonsurgical treatment of laryngeal cancer. It was especially true for advanced T3 glottic laryngeal cancer in which 5-year observed and relative survival showed the best outcome for patients whose initial management was surgery either alone or combined with irradiation. Observed survival rates were 52.9% for surgery alone, 33.1% for irradiation, 55.4 for surgery and adjuvant irradiation, and 50.7% for chemoradiation. The therapeutic concept of neoadjuvant chemotherapy followed by radiation has been evaluated in numerous studies. The Department of Veteran Affairs Laryngeal Cancer Study Group investigated a total of 332 patients with laryngeal carcinoma stages III and IV. 36 Standard treatment total laryngectomy and postoperative radiation was tested against chemotherapy followed by total laryngectomy and radiation. After a median follow-up of 98 months, there were no significant differences compared to standard therapy. Organ preservation was achieved in 31% of the cases. Richard et al 37 performed a similar study in 68 patients presenting with T3 laryngeal carcinoma. Total laryngectomy followed by radiation was compared with induction chemotherapy followed by radiation in good responders and by total laryngectomy in bad responders. The authors observed significantly better recurrence-free and overall survival after primary laryngectomy compared to neoadjuvant chemotherapy. The 2- year survival rates were 69% in the induction chemotherapy group and 84% in the no chemotherapy group. For TLM, good oncologic and functional results have been reported in T2a glottic laryngeal carcinoma. 3 Ambrosch et al 38 observed a 5-year local control rate in 109 patients of 84%, and laryngeal preservation was possible in 96% of the cases. For pt2b and T3 tumors, Blanch et al 39 reported on 107 patients treated with TLM. Five-year overall survival, disease-specific survival, and laryngectomy-free survival were 71%, 79.5%, and 71.4%, respectively. Peretti et al 40 reported 109 patients with pt2 (56 with normal, and 53 with impaired vocal fold mobility) and 11 patients with pt3 treated with laser microsurgery with or without adjuvant chemoradiotherapy. Fiveyear disease-specific survival, local control rate with laser alone, and organ preservation rate was calculated as 98.3%, 85.6%, and 96.1% for T2 and 100%, 71.6%, and 72.7%, for T3 carcinoma, respectively. Vilaseca et al 41 investigated 147 patients with T3 glottic and supraglottic laryngeal carcinoma and observed a disease-specific survival of 86.3% for glottic carcinoma. Vocal fold fixation and cartilage infiltration were independent negative prognostic factors. Grant et al 42 reported the oncologic and functional outcomes of TLM for untreated glottic carcinoma. Twenty-one patients presented with T2, and 5 patients with T3 carcinoma. Local control rate, diseasespecific survival, and overall survival for T2 tumors were 93% each. These good results are in line with previous studies corroborating the relevance of TLM as valuable option for treatment of glottic T2/3 laryngeal cancer. Postoperative voice quality after laser microsurgery, open partial resection, and primary radiotherapy remains controversial. However, discussion of voice quality after different therapeutic regimes is challenging, because neither the selection of patients and the inclusion criteria (surgery T3 vs irradiation T1) nor the methods of voice analysis are comparable. Keilmann et al 43 have observed better voice quality after laser surgery compared to open surgery. After primary radiotherapy, voice quality does not return to normal, as has been reported by Dagli et al. 44 Other authors have stated that there is no difference between voice quality after laser surgery when compared to primary radiotherapy. 45,46 In our experience, postoperative voice quality depends on several factors, such as localization of the tumor and its depth of infiltration. These parameters and the extent of resection between different surgeons influence the amount of resected tissue and thus the functional outcome. This is in line with Vilaseca et al 47 who demonstrated a direct relation of the voice outcome with the amount of resected tissue in patients with T1 glottic laryngeal carcinoma. Other factors are the safety margin chosen by the surgeon, individual wound healing, and the quality of postoperative voice rehabilitation. CONCLUSION Primary transoral laser surgery, in combination with or without selective neck dissection and adjuvant treatment, offers good oncologic and functional results to patients with pt2-t3 glottic carcinoma. This individual therapeutic concept has considerable advantages including lower morbidity, shorter duration of treatment, and patient acceptability. Transoral laser surgery provides local disease control by a differentiation between tumor and healthy tissue allowing oncological radical tumor resection while preserving as much healthy and functionally important tissue as possible. Furthermore, an accurate indication for adjuvant therapy is possible because of intraoperative determination of tumor extent and depth of infiltration. This technique also does allow de-escalation of treatment for those cases deemed to be satisfactorily treated by TLM alone, plus/minus selective neck dissections, a decision based on final pathological assessment. HEAD & NECK DOI /HED JUNE

8 CANIS ET AL. The oncologic results achieved by TLM resection are at least as good compared to those of open partial or total laryngectomy with respect to local control and survival, for both early and advanced stages, whereas those of primary radiotherapy are inferior to both surgical procedures. The complication rate after TLM for advanced glottic cancer is very low, and the functional results regarding swallowing are excellent. In both cases, laser surgery has advantages over open partial surgery and primary radiotherapy. Postoperative voice quality is good to satisfactory, depending on the size of the tumor and the extent of resection and speech therapy. Further benefits are the possibility to integrate transoral laser surgery into any therapeutic concept and the lack of reconstructive surgery. The presented results are very satisfactory, but as it is the data of only one institution, we recommend that it should be validated by a prospective multicenter study. REFERENCES 1. Strong MS, Jako GJ. Laser surgery in the larynx. Early clinical experience with continuous CO 2 laser. Ann Otol Rhinol Laryngol 1972;81: Steiner W. Experience in endoscopic laser surgery of malignant tumours of the upper aero-digestive tract. Adv Otorhinolaryngol 1988;39: Steiner W. Results of curative laser microsurgery of laryngeal carcinomas. Am J Otolaryngol 1993;14: Steiner W, Ambrosch P, Hess CF, Kron M. Organ preservation by transoral laser microsurgery in piriform sinus carcinoma. Otolaryngol Head Neck Surg 2001;124: Steiner W, Fierek O, Ambrosch P, Hommerich CP, Kron M. Transoral laser microsurgery for squamous cell carcinoma of the base of the tongue. Arch Otolaryngol Head Neck Surg 2003;129: Sobin LH, Compton CC. TNM seventh edition: what s new, what s changed: communication from the International Union Against Cancer and the American Joint Committee on Cancer. Cancer 2010;116: Werner JA, Lippert BM, Sch unke M, Rudert H. [Animal experiment studies of laser effects on lymphatic vessels. A contribution to the discussion of laser surgery segmental resection of carcinomas]. [Article in German] Laryngorhinootologie 1995;74: Steiner W, Ambrosch P. Endoscopic laser surgery of the upper aerodigestive tract. Stuttgart, Germany: Thieme; pp Holsinger FC, Diaz EM Jr. Laryngeal preservation in the era of chemoradiation: limitations of the current AJCC staging system. Head Neck 2006; 28: Laccourreye O, Weinstein G, Brasnu D, Trotoux J, Laccourreye H. Vertical partial laryngectomy: a critical analysis of local recurrence. Ann Otol Rhinol Laryngol 1991;100: Som ML. Cordal cancer with extension to vocal process. Laryngoscope 1975;85: Razack MS, Maipang T, Sako K, Bakamjian V, Shedd DP. Management of advanced glottic carcinomas. Am J Surg 1989;158: Bryant GP, Poulsen MG, Tripcony L, Dickie GJ. Treatment decisions in T3N0M0 glottic carcinoma. Int J Radiat Oncol Biol Phys 1995;31: Foote RL, Olsen KD, Buskirk SJ, Stanley RJ, Suman VJ. Laryngectomy alone for T3 glottic cancer. Head Neck 1994;16: Biller HF, Lawson W. Partial laryngectomy for vocal cord cancer with marked limitation or fixation of the vocal cord. Laryngoscope 1986;96: Lesinski SG, Bauer WC, Ogura JH. Hemilaryngectomy for T3 (fixed cord) epidermoid carcinoma of larynx. Laryngoscope 1976;86: Piquet JJ, Desaulty A, Pilliaert JM, Decroix G. [Results of surgical treatment of cancers of the endolarynx]. [Article in French] Acta Otorhinolaryngol Belg 1973;27: Vega SF, Scola B, Vega MF, Martinez T, Scola E. [Laryngeal vertical partial surgery. Surgical techniques. Oncological and functional results]. [Article in Italian] Acta Otorhinolaryngol Ital 1996;16: Chevalier D, Laccourreye O, Brasnu D, Laccourreye H, Piquet JJ. Cricohyoidoepiglottopexy for glottic carcinoma with fixation or impaired motion of the true vocal cord: 5-year oncologic results with 112 patients. Ann Otol Rhinol Laryngol 1997;106: Piquet JJ, Chevalier D. Subtotal laryngectomy with crico-hyoido-epiglottopexy for the treatment of extended glottic carcinomas. Am J Surg 1991; 162: Laccourreye O, Laccourreye L, Muscatello L, Perie S, Weinstein G, Brasnu D. Local failure after supracricoid partial laryngectomy: symptoms, management, and outcome. Laryngoscope 1998;108: Laccourreye O, Brasnu D, Biacabe B, Hans S, Seckin S, Weinstein G. Neoadjuvant chemotherapy and supracricoid partial laryngectomy with cricohyoidopexy for advanced endolaryngeal carcinoma classified as T3-T4: 5- year oncologic results. Head Neck 1998;20: Laccourreye O, Diaz EM Jr, Bassot V, Muscatello L, Garcia D, Brasnu D. A multimodal strategy for the treatment of patients with T2 invasive squamous cell carcinoma of the glottis. Cancer 1999;85: Laccourreye O, Salzer SJ, Brasnu D, Shen W, Laccourreye H, Weinstein GS. Glottic carcinoma with a fixed true vocal cord: outcomes after neoadjuvant chemotherapy and supracricoid partial laryngectomy with cricohyoidoepiglottopexy. Otolaryngol Head Neck Surg 1996;114: Barthel SW, Esclamado RM. Primary radiation therapy for early glottic cancer. Otolaryngol Head Neck Surg 2001;124: Dinshaw KA, Sharma V, Agarwal JP, Ghosh S, Havaldar R. Radiation therapy in T1-T2 glottic carcinoma: influence of various treatment parameters on local control/complications. Int J Radiat Oncol Biol Phys 2000;48: Marshak G, Brenner B, Shvero J, et al. Prognostic factors for local control of early glottic cancer: the Rabin Medical Center retrospective study on 207 patients. Int J Radiat Oncol Biol Phys 1999;43: Mendenhall WM, Parsons JT, Stringer SP, Cassisi NJ, Million RR. T1-T2 vocal cord carcinoma: a basis for comparing the results of radiotherapy and surgery. Head Neck Surg 1988;10: Schwaab G, Mamelle G, Lartigau E, Parise O Jr, Wibault P, Luboinski B. Surgical salvage treatment of T1/T2 glottic carcinoma after failure of radiotherapy. Am J Surg 1994;168: Fein DA, Mendenhall WM, Parsons JT, Million RR. T1-T2 squamous cell carcinoma of the glottic larynx treated with radiotherapy: a multivariate analysis of variables potentially influencing local control. Int J Radiat Oncol Biol Phys 1993;25: Jïrgensen K, Godballe C, Hansen O, Bastholt L. Cancer of the larynx treatment results after primary radiotherapy with salvage surgery in a series of 1005 patients. Acta Oncol 2002;41: Burke LS, Greven KM, McGuirt WT, Case D, Hoen HM, Raben M. Definitive radiotherapy for early glottic carcinoma: prognostic factors and implications for treatment. Int J Radiat Oncol Biol Phys 1997;38: Mendenhall WM, Parsons JT, Mancuso AA, Pameijer FJ, Stringer SP, Cassisi NJ. Definitive radiotherapy for T3 squamous cell carcinoma of the glottic larynx. J Clin Oncol 1997;15: Wylie JP, Sen M, Swindell R, Sykes AJ, Farrington WT, Slevin NJ. Definitive radiotherapy for 114 cases of T3N0 glottic carcinoma: influence of dose-volume parameters on outcome. Radiother Oncol 1999;53: Hoffman HT, Porter K, Karnell LH, et al. Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival. Laryngoscope 2006;116(9 Pt 2 Suppl 111): [No authors listed] Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 1991;324: Richard JM, Sancho Garnier H, Pessey JJ, et al. Randomized trial of induction chemotherapy in larynx carcinoma. Oral Oncol 1998;34: Ambrosch P, R odel R, Kron M, W. S. [The transoral laser surgery of laryngeal cancer. A retrospective analysis of 675 patients gradients]. [Article in German] Onkologe 2001;7: Blanch JL, Vilaseca I, Caballero M, Moragas M, Berenguer J, Bernal Sprekelsen M. Outcome of transoral laser microsurgery for T2-T3 tumors growing in the laryngeal anterior commissure. Head Neck 2011;33: Peretti G, Piazza C, Cocco D, et al. Transoral CO(2) laser treatment for T(is)-T(3) glottic cancer: the University of Brescia experience on 595 patients. Head Neck 2010;32: Vilaseca I, Bernal Sprekelsen M, Luis Blanch J. Transoral laser microsurgery for T3 laryngeal tumors: prognostic factors. Head Neck 2010;32: Grant DG, Salassa JR, Hinni ML, Pearson BW, Hayden RE, Perry WC. Transoral laser microsurgery for untreated glottic carcinoma. Otolaryngol Head Neck Surg 2007;137: Keilmann A, Bergler W, Artzt M, H ormann K. Vocal function following laser and conventional surgery of small malignant vocal fold tumours. J Laryngol Otol 1996;110: Dagli AS, Mahieu HF, Festen JM. Quantitative analysis of voice quality in early glottic laryngeal carcinomas treated with radiotherapy. Eur Arch Otorhinolaryngol 1997;254: Brandenburg JH. Laser cordotomy versus radiotherapy: an objective cost analysis. Ann Otol Rhinol Laryngol 2001;110: Delsupehe KG, Zink I, Lejaegere M, Bastian RW. Voice quality after narrow-margin laser cordectomy compared with laryngeal irradiation. Otolaryngol Head Neck Surg 1999;121: Vilaseca I, Huerta P, Blanch JL, Fernandez Planas AM, Jimenez C, Bernal Sprekelsen M. Voice quality after CO2 laser cordectomy what can we really expect? Head Neck 2008;30: HEAD & NECK DOI /HED JUNE 2014