Eur Arch Otorhinolaryngol DOI 10.1007/s00405-015-3547-3
LARYNGOLOGY
Management of surgical margins after endoscopic laser surgery for early glottic cancers: a multicentric evaluation in French-speaking European countries Nicolas Fakhry • Se´bastien Vergez • Emmanuel Babin • Karine Baumstarck • Laure Santini • Patrick Dessi • Antoine Giovanni
Received: 15 December 2014 / Accepted: 3 February 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract The aim of this study was to evaluate the practices of ENT surgeons for the management of surgical margins after endoscopic laser surgery for early glottic cancers. A questionnaire was sent to different surgeons managing cancers of the larynx in France, Belgium and Switzerland. A descriptive and comparative analysis of practices across centers was performed. Sixty-nine surgeons completed the questionnaire (58 in France, 10 in Belgium and 1 in Switzerland). In case of very close or equivocal resection margins after definitive histological examination, 67 % of surgeons perform close follow-up, 28 % further treatment and 5 % had no opinion. Factors resulting in a significant change in the management of equivocal or very close margins were: the country of origin (p = 0.011), the specialty of the multidisciplinary team leader (p = 0.001), the fact that radiation equipment is located in the same center (p = 0.027) and the access to
IMRT technique (p = 0.027). In case of positive resection margins, 80 % of surgeons perform further treatment, 15 % surveillance, and 5 % had no opinion. The only factor resulting in a significant change in the management of positive margins was the number of cancers of the larynx treated per year (p = 0.011). It is important to spare, on one hand equivocal or very close margins and on the other hand, positive margins. Postoperative management should be discussed depending on intraoperative findings, patient, practices of multidisciplinary team, and surgeon experience. This management remains non-consensual and writing a good practice guideline could be useful. Keywords Cancer Larynx Head and neck Endoscopic surgery Radiotherapy
Introduction This study was presented at the 46th annual meeting of the SFCCF (French Society of Head and Neck Cancer), November 22–23 2013, Liege, Belgium and at the 121st annual meeting of the SFORL (French ENT Society), October 11–13 2014, Paris, France.
Management of surgical margins following endoscopic laser surgery of early glottic carcinoma remains controversial.
N. Fakhry (&) L. Santini P. Dessi A. Giovanni Service d’ORL et Chirurgie Cervico-Faciale, Assistance Publique-Hoˆpitaux de Marseille (AP-HM), Aix-Marseille Universite´, Centre Hospitalier Universitaire (CHU) la Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France e-mail: [email protected]
E. Babin Service d’ORL et Chirurgie Cervico-Faciale, CHU Coˆte de Nacre, avenue de la Coˆte de Nacre, 14033 Caen Cedex 9, France
N. Fakhry L. Santini A. Giovanni LPL, Laboratoire Parole et Langage, CNRS UMR 7309, Aix-Marseille Universite´, Aix En Provence, France S. Vergez Service d’ORL et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire Rangueil-Larrey, 24 chemin de Pouvourville, 31059 Toulouse Cedex 09, France
K. Baumstarck Unite´ d’Aide Me´thodologique a` la Recherche Clinique, Assistance Publique-Hoˆpitaux de Marseille, Centre Hospitalier Universitaire La Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France K. Baumstarck Faculte´ de Me´decine, EA 3279 ‘Qualite´ de Vie Concepts, Usages et Limites, De´terminants’ Aix-Marseille Universite´, 27 bd Jean Moulin, 13385 Marseille Cedex, France
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While no complementary treatment such as radiation therapy is usually indicated when resection margins are clear [1, 2], the decision of complementary treatment is somewhat confusing in other cases particularly when margins are equivocal or positives. The purpose of this study was to evaluate, by questionnaire, the practices of ENT surgeons managing cancers of the larynx in French-speaking Europe and to analyze their decision-making criteria in case of very close (or equivocal) or positive margins after endoscopic laser surgery.
Materials and methods A questionnaire was e-mailed to surgeons treating cancers of the larynx and belonging to French GETTEC study group (Groupe d’Etude des Tumeurs de la Teˆte et du Cou, i.e. Head and Neck tumors Study Group) or to SFCCF (Socie´te´ Franc¸aise de Carcinologie Cervico-Faciale, i.e. French Society of Cervico-Facial Carcinology). The questionnaire covered three countries: France, Belgium and Switzerland. One questionnaire per medical center was taken into account. First part of our study, previously published [3], focused on the practitioner’s type of activity and on his/her therapeutic strategy for the management of early glottic cancers (surgery or radiotherapy). The present part focused on their surgical strategy and management of margins during and after endoscopic resection of early glottic carcinomas. Type of activity Questions focused on the mode of activity (private, hospital or university teaching hospital), the number of cancers of the larynx treated per year, the proportion of oncology in ENT activity, the type of equipment (laser, robot, radiation equipment) and the specialty of the multidisciplinary team leader (ENT, radiation therapist, medical oncologist). The final questions related to knowledge of the cost of the different treatments and whether it had any influence on treatment decisions.
Statistical analysis Statistical analyses were performed using the SPSS version 15.0 software package (SPSS inc., Chicago IL, USA). Statistical significance was defined as p \ 0.05. Sample characteristics were detailed using frequencies for qualitative variables. Proportions were compared using Chi square or Fisher’s exact tests.
Results Sixty-nine questionnaires were completed: 58 in France (including all French University Teaching Hospitals), 10 in Belgium and one in Switzerland. Type of activity Surgeons completing the questionnaire practiced in a university teaching hospital in 38 cases, in an anticancer center in 7 cases, in a non-university public hospital in 12 cases and in a private center in 12 cases. Forty-six centers (68 %) treated fewer than 50 laryngeal cancers per year, while 22 (32 %) treated more than 50. The proportion of cancer in the overall practice of the surgeons was less than 20 % for 7.5 % of the centers, between 20 and 50 % for 38 %, between 50 and 80 % for 31 % and 80 % for 23.5 %. More than 90 % of the centers were equipped with a CO2 laser (91.5 %) and 45 % were equipped with a robot. Eighty-seven per cent of the surgeons also treated benign laryngeal pathologies (Phonosurgery). The radiotherapy department was located in the same institution in 53.5 % of cases. Among the 46.5 % of cases where radiotherapy was not available in the same center, it was located in the same city in 78 % of cases. Ninety-one per cent of centers had access to conformal intensity-modulated radiation therapy (IMRT), and 39 % systematically used this technique for treatment of laryngeal cancer. The multidisciplinary team leader was an ENT surgeon in 78.5 % of cases, a radiotherapist in 11.5 % and a medical oncologist in 10 %. Finally, 71 % of surgeons declared they knew the cost of the different treatment strategies and 39 % said they consider this cost when deciding on treatment.
Surgical strategy and management of margins Regarding the surgical technique, questions focused on the management of resection margins during the surgical procedure: frozen section analysis of margins and achievement of additional resection after tumor removal. It was then asked to specify the strategy in case of very close or equivocal resection margins and in case of positive margins after definitive histological examination.
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Surgical management of margins during initial procedure During endoscopic surgery for early glottic cancer, 10 % of surgeons surveyed in our study reported systematically perform frozen section of margins, 33 % occasionally and 57 % never. Thirty-four percent reported systematically perform additional resection after tumor removal (without
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frozen section), 60 % occasionally based on intraoperative findings and 6 % never.
Table 1 Factors resulting in a significant change in the management of equivocal margins Treatment (%)
Management of equivocal (or very close) definitive margins In case of very close or equivocal resection margins after definitive histological examination, 67 % of surgeons perform close follow-up, 28 % further treatment and 5 % had no opinion (Fig. 1). Among surgeons achieving surveillance, 48 % perform a follow-up by physical examination (nasal fiber endoscopy), 43 % perform systematically an endoscopy under general anesthesia and 9 %, do one or the other (case by case discussion). Among surgeons achieving further treatment, it was preferentially further resection using endoscopic laser surgery in 52 % of cases, radiotherapy in 26 %, surgery using external approach in 11 % and in 11 % of cases the surgeon had no clear opinion. Factors resulting in a significant change in the management of equivocal or very close margins were (Table 1): – –
–
–
The country of origin: French surgeons achieve more follow-up than Belgian (77 vs. 40 %, p = 0.011) The specialty of the multidisciplinary team leader: 82 % of close follow-up when the leader is an ENT surgeon vs. 28 % when the leader is a radiation therapist or a medical oncologist (p = 0.001). The fact that radiation equipment is located in the same center: 59 % of close follow-up when radiation equipment is located in the same center vs. 84 % if not (p = 0.027). The access to IMRT technique: 56 % of close followup in case of access to IMRT technique vs. 83 % if not (p = 0.027).
No criteria related to the type of medical activity were found to have a significant influence on treatment strategy: activity mode (p = 0.36), number of cancers of the larynx treated each year (p = 0.56), percentage of cancer in ENT
Fig. 1 Management of very close or equivocal margins
Surveillance (%)
p
0.011
Country France
23
77
Belgium
60
40
ENT surgeon
18
82
Other
72
28
MDT leader
Location of radiotherapy Same institution 41 Other
59
16
84
Yes
44
56
No
17
83
0.001
0.027
Use of IRMT 0.027
activity (p = 0.74), and awareness of the cost of treatment (p = 0.23). Management of positive margins In case of positive resection margins after definitive histological examination, 80 % of surgeons perform further treatment, 15 % follow-up, and 5 % had no opinion (Fig. 2). Among surgeons achieving further treatment, it was preferentially further resection using endoscopic laser surgery in 49 % of cases, radiotherapy in 20 %, surgery using external approach in 22 % and in 9 % of cases the surgeon had no clear opinion. Among surgeons achieving follow-up, 30 % perform a follow-up by physical examination (nasal fiber endoscopy) and 70 % perform systematically an endoscopy under general anesthesia. The only factor resulting in a significant change in the management of positive margins was the number of cancers of the larynx treated per year: centers treating more than 50 laryngeal cancers per year achieve more follow-up than centers treating fewer than 50, (32 vs. 7 %, p = 0.011) (Table 2).
Fig. 2 Management of very close or equivocal margins
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Discussion Our study showed that management of surgical margins following endoscopic laser resection of early glottic carcinoma is very heterogeneous between different centers and without any consensus. We know that margins are often very close or equivocal because of the need to spare as much tissue as possible for functional reasons, making them hard to analyze [2, 4, 5], but the large number of margins judged positive or equivocal seems not to be reflected clinically in a corresponding number of recurrences or treatment failures. In a previous study, we have assessed the prognostic value of margin status in terms of overall and of recurrence-free survival in a population of T1a glottic carcinoma operated by endoscopic laser surgery at our institution [6]. Among 64 patients treated at our institution between 1996 and 2006, 40 (62.5 %) had negative margins while 24 (37.5 %) had positive margins. Overall 5-year survival was 97 % (95 % in group with negative margins and 100 % in group with positive margins). Five-year recurrence-free survival was 94 % (91.7 % in group with negative margins and 95 % in group with positive margins). There was no significant difference in overall or recurrence-free survival according to resection margin histological status in our series. In 2000, Peretti et al. [7] had already showed that positive margins did not affect local control. This was confirmed in other studies [2, 8, 9]. The problem for the clinician is then to decide between close follow-up, surgical revision and radiation therapy in case of equivocal or positive margins. Several authors recommended intraoperative frozen section biopsy. Remacle et al. [10] found they had a negative predictive value of 95 %, enabling cordectomy to be extended in 10 % of cases. In a recent study, Fang et al. [11] have analyzed the prognostic value of positive intraoperative frozen sections in 75 patients. They have shown that initially positive frozen section margins, despite enlarging the cordectomy field to obtain negative margins, were statistically significant predictors of recurrence. However frozen section runs up against practical problems of availability in certain centers and technical difficulties related to the unreliability of extemporaneous small fragment analysis: it is not unusual for final histological
Table 2 Factors resulting in a significant change in the management of positive margins Treatment (%)
Surveillance (%)
p
0.011
Number of laryngeal cancers/year [50
68
32
\50
93
7
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analysis to be less favorable than the extemporaneous analysis, discovering non-negative margins [1]. In case of equivocal or positive margins, most authors recommend control endoscopy under general anesthesia with targeted biopsy. In 2007, Jacke¨l et al. [12] reported that 70 out of 382 patients (18 %) undergoing systematic revision for positive margins showed neoplastic cells in the revision specimens. In a series of 181 patients operated on for early glottic carcinoma systematically scheduled for two endoscopic second looks at 10 weeks and 16–20 weeks after initial surgery, Preuss et al. [13] have found carcinoma in 5.1 % of all patients within the first and in 11.5 % of all patients within the second second-look microlaryngoscopy, although the preoperative indirect laryngoscopy was inconspicuous in most cases. Peretti et al. [14], in a study of 595 patients, reported that deep positive margins after laser revision had a negative impact on local control and laryngeal conservation without, however, affecting specific survival after treatment of residual disease. The recommended interval between initial surgery and revision is 10 weeks [5, 12, 14]. This interval allows the larynx to heal and provides histologically reliable results even though, in case of negative biopsies, a careful follow-up is necessary because these biopsies remain difficult to interpret due to small specimen size, thermal effects induced by the laser and/or tissue retraction. Moreover there may be neoplastic cells in between the biopsy sites, making this safeguard illusory. In our opinion, patients with equivocal (or very close) margins should be managed differently from patients with positive margins. In our study, 67 % of surgeons perform follow-up in case of very close or equivocal margins while only 15 % perform surveillance in case of positive margins. The goal is to avoid overtreatment of patients to limit adverse effects that can cause impairment of quality of life while providing optimal tumor control rate. The surgeon, however, must deal with the difficulties of the histological examination, hampered by small fragment analysis and tissue retraction problems. It is clear that the intraoperative findings should be taken into account in the decision to propose further treatment or monitoring. Indeed, if the surgeon has performed a macroscopically satisfactory surgery, it is more likely to monitor the patient than treat in case of close or equivocal margins. This explains the difference of strategy, in our study, depending on the multidisciplinary team leader because when he is surgeon, he will probably have easier way to imposing a monitoring strategy for close or equivocal margins if he believes he has made a satisfactory resection during surgery. Our study has also shown that radiation equipment and the access to IMRT technique resulted in a significant change in the management. The methods of follow-up were also very heterogeneous in our study (nasal fiber endoscopy or
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endoscopy under general anesthesia). They also depend on factors such as the ease of patient examination with nasal fiber endoscope and patient compliance. Clinical follow-up eventually in combination with imaging seems to be a good strategy when the patient is easily examinable and is compliant for close monitoring. Endoscopy under general anesthesia should be performed otherwise. In case of positive margins, it seems more difficult to propose a close follow-up (15 % in our study). It can sometimes be suggested, case by case, depending on the intraoperative findings and depend very much, in our study, on surgeon experience. Achieving additional resection, during the same procedure, after tumor removal with (10–33 % in our study) or without (34–60 % in our study) frozen section appears to be a good option because if it is sometimes difficult to characterize the margins on surgical specimen, the presence of carcinoma in additional resection specimens should encourage to offer further treatment or at least a second look under general anesthesia. The treatment strategy remains non-consensual and depends on patient, practices of multidisciplinary team, type of equipment, and surgeon experience. Finally, it is important to emphasize that this study shows practices of surgeons from French-speaking Europe and that it can exist differences of strategies with other parts of Europe or with Anglo-Saxon’s countries. The main problem is there is currently no consensus on the strategies for the management of surgical margins after endoscopic laser surgery for early glottic cancers. Indeed our work should not be read as guidelines but as a reflection on current treatment preferences of a research group (SFCCF and GETTEC).
Conclusion Management of surgical margins during and following endoscopic laser surgery of early glottic carcinoma remains non-consensual. In case of close or equivocal margins, clinical follow-up eventually in combination with imaging seems to be a good strategy when the patient is easily examinable and is compliant for close monitoring. Endoscopy under general anesthesia should be performed otherwise, 8–10 weeks after initial surgery. In case of positive margins, except for selective cases, further treatment or at least a second look under general anesthesia must be performed. Achieving additional resection during
the initial procedure, after tumor removal, may help to apprehend margins and to define the best postoperative strategy. Conflict of interest financial disclosure.
The authors declare no conflict of interest or
References 1. Jones AS, Fish B, Fenton JE et al (2004) The treatment of early laryngeal cancers (T1-T2 N0): surgery or irradiation? Head Neck 26:127–135 2. Mendenhall WM, Werning JW, Hinerman RW et al (2004) Management of T1-T2 glottic carcinomas. Cancer 100:1786– 1792 3. Fakhry N, Vergez S, Baumstarck K et al (2015) Multicentric evaluation of strategies for treatment of T1a glottic carcinomas. Eur Arch Otorhinolaryngol 272:143–148 4. Gallo A, de Vincentiis M, Manciocco V et al (2002) CO2 laser cordectomy for early-stage glottic carcinoma: a long-term followup of 156 cases. Laryngoscope 112:370–374 5. Sigston E, de Mones E, Babin E et al (2006) Early-stage glottic cancer oncological results and margins in laser cordectomy. Arch Otolaryngol Head Neck Surg 132:147–152 6. Michel J, Fakhry N, Duflo S, Lagier A, Mancini J, Dessi P, Giovanni A (2011) Prognostic value of the status of resection margins after endoscopic laser cordectomy for T1a glottic carcinoma. Eur Ann Otorhinolaryngol Head Neck Dis 128:297–300 7. Peretti G, Nicolai P, De Zinis LOR et al (2000) Endoscopic CO2 laser excision for Tis, T1, and T2 glottic carcinomas: cure rate and prognostic factors. Otolaryngol Head Neck Surg 123:124– 131 8. Crespo AN, Chone CT, Gripp FM et al (2006) Role of margin status in recurrence after CO2 laser endoscopic resection of early glottis cancer. Acta Otolaryngol 126:306–310 9. Mortuaire G, Francois J, Wiel E et al (2006) Local recurrence after CO2 laser cordectomy for early glottic carcinoma. Laryngoscope 116:101–105 10. Remacle M, Matar N, Delos M et al (2010) Is frozen section reliable in transoral CO2 laser-assisted cordectomies? Eur Arch Otorhinolaryngol 267:397–400 11. Fang TJ, Courey MS, Liao CT, Yen TC, Li HY (2013) Frozen margin analysis as a prognosis predictor in early glottic cancer by laser cordectomy. Laryngoscope 123:1490–1495 12. Jackel MC, Ambrosch P, Martin A et al (2007) Impact of reresection for inadequate margins on the prognosis of upper aerodigestive tract cancer treated by laser microsurgery. Laryngoscope 117:350–356 13. Preuss SF, Cramer K, Drebber U, Klussmann JP, Eckel HE, Guntinas-Lichius O (2009) Second-look microlaryngoscopy to detect residual carcinoma in patients after laser surgery for T1 and T2 laryngeal cancer. Acta Otolaryngol 129:881–885 14. Peretti G, Piazza C, Cocco D et al (2010) Transoral CO2 laser treatment for T-is-T-3 glottic cancer: the University of Brescia experience on 595 patients. Head Neck 32:977–983
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LARYNGOLOGY
Management of surgical margins after endoscopic laser surgery for early glottic cancers: a multicentric evaluation in French-speaking European countries Nicolas Fakhry • Se´bastien Vergez • Emmanuel Babin • Karine Baumstarck • Laure Santini • Patrick Dessi • Antoine Giovanni
Received: 15 December 2014 / Accepted: 3 February 2015 Ó Springer-Verlag Berlin Heidelberg 2015
Abstract The aim of this study was to evaluate the practices of ENT surgeons for the management of surgical margins after endoscopic laser surgery for early glottic cancers. A questionnaire was sent to different surgeons managing cancers of the larynx in France, Belgium and Switzerland. A descriptive and comparative analysis of practices across centers was performed. Sixty-nine surgeons completed the questionnaire (58 in France, 10 in Belgium and 1 in Switzerland). In case of very close or equivocal resection margins after definitive histological examination, 67 % of surgeons perform close follow-up, 28 % further treatment and 5 % had no opinion. Factors resulting in a significant change in the management of equivocal or very close margins were: the country of origin (p = 0.011), the specialty of the multidisciplinary team leader (p = 0.001), the fact that radiation equipment is located in the same center (p = 0.027) and the access to
IMRT technique (p = 0.027). In case of positive resection margins, 80 % of surgeons perform further treatment, 15 % surveillance, and 5 % had no opinion. The only factor resulting in a significant change in the management of positive margins was the number of cancers of the larynx treated per year (p = 0.011). It is important to spare, on one hand equivocal or very close margins and on the other hand, positive margins. Postoperative management should be discussed depending on intraoperative findings, patient, practices of multidisciplinary team, and surgeon experience. This management remains non-consensual and writing a good practice guideline could be useful. Keywords Cancer Larynx Head and neck Endoscopic surgery Radiotherapy
Introduction This study was presented at the 46th annual meeting of the SFCCF (French Society of Head and Neck Cancer), November 22–23 2013, Liege, Belgium and at the 121st annual meeting of the SFORL (French ENT Society), October 11–13 2014, Paris, France.
Management of surgical margins following endoscopic laser surgery of early glottic carcinoma remains controversial.
N. Fakhry (&) L. Santini P. Dessi A. Giovanni Service d’ORL et Chirurgie Cervico-Faciale, Assistance Publique-Hoˆpitaux de Marseille (AP-HM), Aix-Marseille Universite´, Centre Hospitalier Universitaire (CHU) la Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France e-mail: [email protected]
E. Babin Service d’ORL et Chirurgie Cervico-Faciale, CHU Coˆte de Nacre, avenue de la Coˆte de Nacre, 14033 Caen Cedex 9, France
N. Fakhry L. Santini A. Giovanni LPL, Laboratoire Parole et Langage, CNRS UMR 7309, Aix-Marseille Universite´, Aix En Provence, France S. Vergez Service d’ORL et Chirurgie Cervico-Faciale, Centre Hospitalier Universitaire Rangueil-Larrey, 24 chemin de Pouvourville, 31059 Toulouse Cedex 09, France
K. Baumstarck Unite´ d’Aide Me´thodologique a` la Recherche Clinique, Assistance Publique-Hoˆpitaux de Marseille, Centre Hospitalier Universitaire La Timone, 264 rue Saint Pierre, 13385 Marseille Cedex 05, France K. Baumstarck Faculte´ de Me´decine, EA 3279 ‘Qualite´ de Vie Concepts, Usages et Limites, De´terminants’ Aix-Marseille Universite´, 27 bd Jean Moulin, 13385 Marseille Cedex, France
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While no complementary treatment such as radiation therapy is usually indicated when resection margins are clear [1, 2], the decision of complementary treatment is somewhat confusing in other cases particularly when margins are equivocal or positives. The purpose of this study was to evaluate, by questionnaire, the practices of ENT surgeons managing cancers of the larynx in French-speaking Europe and to analyze their decision-making criteria in case of very close (or equivocal) or positive margins after endoscopic laser surgery.
Materials and methods A questionnaire was e-mailed to surgeons treating cancers of the larynx and belonging to French GETTEC study group (Groupe d’Etude des Tumeurs de la Teˆte et du Cou, i.e. Head and Neck tumors Study Group) or to SFCCF (Socie´te´ Franc¸aise de Carcinologie Cervico-Faciale, i.e. French Society of Cervico-Facial Carcinology). The questionnaire covered three countries: France, Belgium and Switzerland. One questionnaire per medical center was taken into account. First part of our study, previously published [3], focused on the practitioner’s type of activity and on his/her therapeutic strategy for the management of early glottic cancers (surgery or radiotherapy). The present part focused on their surgical strategy and management of margins during and after endoscopic resection of early glottic carcinomas. Type of activity Questions focused on the mode of activity (private, hospital or university teaching hospital), the number of cancers of the larynx treated per year, the proportion of oncology in ENT activity, the type of equipment (laser, robot, radiation equipment) and the specialty of the multidisciplinary team leader (ENT, radiation therapist, medical oncologist). The final questions related to knowledge of the cost of the different treatments and whether it had any influence on treatment decisions.
Statistical analysis Statistical analyses were performed using the SPSS version 15.0 software package (SPSS inc., Chicago IL, USA). Statistical significance was defined as p \ 0.05. Sample characteristics were detailed using frequencies for qualitative variables. Proportions were compared using Chi square or Fisher’s exact tests.
Results Sixty-nine questionnaires were completed: 58 in France (including all French University Teaching Hospitals), 10 in Belgium and one in Switzerland. Type of activity Surgeons completing the questionnaire practiced in a university teaching hospital in 38 cases, in an anticancer center in 7 cases, in a non-university public hospital in 12 cases and in a private center in 12 cases. Forty-six centers (68 %) treated fewer than 50 laryngeal cancers per year, while 22 (32 %) treated more than 50. The proportion of cancer in the overall practice of the surgeons was less than 20 % for 7.5 % of the centers, between 20 and 50 % for 38 %, between 50 and 80 % for 31 % and 80 % for 23.5 %. More than 90 % of the centers were equipped with a CO2 laser (91.5 %) and 45 % were equipped with a robot. Eighty-seven per cent of the surgeons also treated benign laryngeal pathologies (Phonosurgery). The radiotherapy department was located in the same institution in 53.5 % of cases. Among the 46.5 % of cases where radiotherapy was not available in the same center, it was located in the same city in 78 % of cases. Ninety-one per cent of centers had access to conformal intensity-modulated radiation therapy (IMRT), and 39 % systematically used this technique for treatment of laryngeal cancer. The multidisciplinary team leader was an ENT surgeon in 78.5 % of cases, a radiotherapist in 11.5 % and a medical oncologist in 10 %. Finally, 71 % of surgeons declared they knew the cost of the different treatment strategies and 39 % said they consider this cost when deciding on treatment.
Surgical strategy and management of margins Regarding the surgical technique, questions focused on the management of resection margins during the surgical procedure: frozen section analysis of margins and achievement of additional resection after tumor removal. It was then asked to specify the strategy in case of very close or equivocal resection margins and in case of positive margins after definitive histological examination.
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Surgical management of margins during initial procedure During endoscopic surgery for early glottic cancer, 10 % of surgeons surveyed in our study reported systematically perform frozen section of margins, 33 % occasionally and 57 % never. Thirty-four percent reported systematically perform additional resection after tumor removal (without
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frozen section), 60 % occasionally based on intraoperative findings and 6 % never.
Table 1 Factors resulting in a significant change in the management of equivocal margins Treatment (%)
Management of equivocal (or very close) definitive margins In case of very close or equivocal resection margins after definitive histological examination, 67 % of surgeons perform close follow-up, 28 % further treatment and 5 % had no opinion (Fig. 1). Among surgeons achieving surveillance, 48 % perform a follow-up by physical examination (nasal fiber endoscopy), 43 % perform systematically an endoscopy under general anesthesia and 9 %, do one or the other (case by case discussion). Among surgeons achieving further treatment, it was preferentially further resection using endoscopic laser surgery in 52 % of cases, radiotherapy in 26 %, surgery using external approach in 11 % and in 11 % of cases the surgeon had no clear opinion. Factors resulting in a significant change in the management of equivocal or very close margins were (Table 1): – –
–
–
The country of origin: French surgeons achieve more follow-up than Belgian (77 vs. 40 %, p = 0.011) The specialty of the multidisciplinary team leader: 82 % of close follow-up when the leader is an ENT surgeon vs. 28 % when the leader is a radiation therapist or a medical oncologist (p = 0.001). The fact that radiation equipment is located in the same center: 59 % of close follow-up when radiation equipment is located in the same center vs. 84 % if not (p = 0.027). The access to IMRT technique: 56 % of close followup in case of access to IMRT technique vs. 83 % if not (p = 0.027).
No criteria related to the type of medical activity were found to have a significant influence on treatment strategy: activity mode (p = 0.36), number of cancers of the larynx treated each year (p = 0.56), percentage of cancer in ENT
Fig. 1 Management of very close or equivocal margins
Surveillance (%)
p
0.011
Country France
23
77
Belgium
60
40
ENT surgeon
18
82
Other
72
28
MDT leader
Location of radiotherapy Same institution 41 Other
59
16
84
Yes
44
56
No
17
83
0.001
0.027
Use of IRMT 0.027
activity (p = 0.74), and awareness of the cost of treatment (p = 0.23). Management of positive margins In case of positive resection margins after definitive histological examination, 80 % of surgeons perform further treatment, 15 % follow-up, and 5 % had no opinion (Fig. 2). Among surgeons achieving further treatment, it was preferentially further resection using endoscopic laser surgery in 49 % of cases, radiotherapy in 20 %, surgery using external approach in 22 % and in 9 % of cases the surgeon had no clear opinion. Among surgeons achieving follow-up, 30 % perform a follow-up by physical examination (nasal fiber endoscopy) and 70 % perform systematically an endoscopy under general anesthesia. The only factor resulting in a significant change in the management of positive margins was the number of cancers of the larynx treated per year: centers treating more than 50 laryngeal cancers per year achieve more follow-up than centers treating fewer than 50, (32 vs. 7 %, p = 0.011) (Table 2).
Fig. 2 Management of very close or equivocal margins
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Discussion Our study showed that management of surgical margins following endoscopic laser resection of early glottic carcinoma is very heterogeneous between different centers and without any consensus. We know that margins are often very close or equivocal because of the need to spare as much tissue as possible for functional reasons, making them hard to analyze [2, 4, 5], but the large number of margins judged positive or equivocal seems not to be reflected clinically in a corresponding number of recurrences or treatment failures. In a previous study, we have assessed the prognostic value of margin status in terms of overall and of recurrence-free survival in a population of T1a glottic carcinoma operated by endoscopic laser surgery at our institution [6]. Among 64 patients treated at our institution between 1996 and 2006, 40 (62.5 %) had negative margins while 24 (37.5 %) had positive margins. Overall 5-year survival was 97 % (95 % in group with negative margins and 100 % in group with positive margins). Five-year recurrence-free survival was 94 % (91.7 % in group with negative margins and 95 % in group with positive margins). There was no significant difference in overall or recurrence-free survival according to resection margin histological status in our series. In 2000, Peretti et al. [7] had already showed that positive margins did not affect local control. This was confirmed in other studies [2, 8, 9]. The problem for the clinician is then to decide between close follow-up, surgical revision and radiation therapy in case of equivocal or positive margins. Several authors recommended intraoperative frozen section biopsy. Remacle et al. [10] found they had a negative predictive value of 95 %, enabling cordectomy to be extended in 10 % of cases. In a recent study, Fang et al. [11] have analyzed the prognostic value of positive intraoperative frozen sections in 75 patients. They have shown that initially positive frozen section margins, despite enlarging the cordectomy field to obtain negative margins, were statistically significant predictors of recurrence. However frozen section runs up against practical problems of availability in certain centers and technical difficulties related to the unreliability of extemporaneous small fragment analysis: it is not unusual for final histological
Table 2 Factors resulting in a significant change in the management of positive margins Treatment (%)
Surveillance (%)
p
0.011
Number of laryngeal cancers/year [50
68
32
\50
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analysis to be less favorable than the extemporaneous analysis, discovering non-negative margins [1]. In case of equivocal or positive margins, most authors recommend control endoscopy under general anesthesia with targeted biopsy. In 2007, Jacke¨l et al. [12] reported that 70 out of 382 patients (18 %) undergoing systematic revision for positive margins showed neoplastic cells in the revision specimens. In a series of 181 patients operated on for early glottic carcinoma systematically scheduled for two endoscopic second looks at 10 weeks and 16–20 weeks after initial surgery, Preuss et al. [13] have found carcinoma in 5.1 % of all patients within the first and in 11.5 % of all patients within the second second-look microlaryngoscopy, although the preoperative indirect laryngoscopy was inconspicuous in most cases. Peretti et al. [14], in a study of 595 patients, reported that deep positive margins after laser revision had a negative impact on local control and laryngeal conservation without, however, affecting specific survival after treatment of residual disease. The recommended interval between initial surgery and revision is 10 weeks [5, 12, 14]. This interval allows the larynx to heal and provides histologically reliable results even though, in case of negative biopsies, a careful follow-up is necessary because these biopsies remain difficult to interpret due to small specimen size, thermal effects induced by the laser and/or tissue retraction. Moreover there may be neoplastic cells in between the biopsy sites, making this safeguard illusory. In our opinion, patients with equivocal (or very close) margins should be managed differently from patients with positive margins. In our study, 67 % of surgeons perform follow-up in case of very close or equivocal margins while only 15 % perform surveillance in case of positive margins. The goal is to avoid overtreatment of patients to limit adverse effects that can cause impairment of quality of life while providing optimal tumor control rate. The surgeon, however, must deal with the difficulties of the histological examination, hampered by small fragment analysis and tissue retraction problems. It is clear that the intraoperative findings should be taken into account in the decision to propose further treatment or monitoring. Indeed, if the surgeon has performed a macroscopically satisfactory surgery, it is more likely to monitor the patient than treat in case of close or equivocal margins. This explains the difference of strategy, in our study, depending on the multidisciplinary team leader because when he is surgeon, he will probably have easier way to imposing a monitoring strategy for close or equivocal margins if he believes he has made a satisfactory resection during surgery. Our study has also shown that radiation equipment and the access to IMRT technique resulted in a significant change in the management. The methods of follow-up were also very heterogeneous in our study (nasal fiber endoscopy or
Eur Arch Otorhinolaryngol
endoscopy under general anesthesia). They also depend on factors such as the ease of patient examination with nasal fiber endoscope and patient compliance. Clinical follow-up eventually in combination with imaging seems to be a good strategy when the patient is easily examinable and is compliant for close monitoring. Endoscopy under general anesthesia should be performed otherwise. In case of positive margins, it seems more difficult to propose a close follow-up (15 % in our study). It can sometimes be suggested, case by case, depending on the intraoperative findings and depend very much, in our study, on surgeon experience. Achieving additional resection, during the same procedure, after tumor removal with (10–33 % in our study) or without (34–60 % in our study) frozen section appears to be a good option because if it is sometimes difficult to characterize the margins on surgical specimen, the presence of carcinoma in additional resection specimens should encourage to offer further treatment or at least a second look under general anesthesia. The treatment strategy remains non-consensual and depends on patient, practices of multidisciplinary team, type of equipment, and surgeon experience. Finally, it is important to emphasize that this study shows practices of surgeons from French-speaking Europe and that it can exist differences of strategies with other parts of Europe or with Anglo-Saxon’s countries. The main problem is there is currently no consensus on the strategies for the management of surgical margins after endoscopic laser surgery for early glottic cancers. Indeed our work should not be read as guidelines but as a reflection on current treatment preferences of a research group (SFCCF and GETTEC).
Conclusion Management of surgical margins during and following endoscopic laser surgery of early glottic carcinoma remains non-consensual. In case of close or equivocal margins, clinical follow-up eventually in combination with imaging seems to be a good strategy when the patient is easily examinable and is compliant for close monitoring. Endoscopy under general anesthesia should be performed otherwise, 8–10 weeks after initial surgery. In case of positive margins, except for selective cases, further treatment or at least a second look under general anesthesia must be performed. Achieving additional resection during
the initial procedure, after tumor removal, may help to apprehend margins and to define the best postoperative strategy. Conflict of interest financial disclosure.
The authors declare no conflict of interest or
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