Abstract
Objective
Survival of patients with advanced laryngeal squamous cell carcinoma (LSCC) remains poor and management protocols warrant further development. We thus investigated treatment and outcome‐related factors for LSCC in Stockholm, Sweden.
Methods
In a retrospective setting, 520 patients with LSCC diagnosed during 2000–2014, were included. Data on stage, treatment, and outcome were correlated with recurrence‐free and overall survival (RFS and OS, respectively).
Results
Five‐year OS for all patients was 65%. Five‐year RFS for T1a, T1b, T2, T3, and T4 glottic LSCC was 90%, 91%, 77%, 47%, and 80%, respectively. The corresponding figures for T1, T2, T3, and T4 supraglottic LSCC were 64%, 66%, 64%, and 86%.
Conclusion
Patients with a T3 glottic LSCC had unexpectedly poor survival, especially when compared with patients with a T4 tumor. Patients with T4 disease were primarily treated with laryngectomy and postoperative radiotherapy (RT)/chemoradiotherapy (CRT), while most patients with T3 LSCC were treated with RT/CRT.
Keywords: clinical outcome, glottic, head and neck cancer, laryngeal squamous cell carcinoma, supraglottic
A retrospective single‐center cohort study was performed consisting 520 patients diagnosed with laryngeal squamous cell carcinoma in Stockholm during 15 years. The study showed an unexpectedly poor survival for patients with T3 glottic laryngeal cancer, with a significantly poorer prognosis compared with patients with a T4 tumor.
1. INTRODUCTION
Laryngeal cancer is the 18th leading cause of cancer‐treated Disability‐Adjusted Life Years (DALYs) globally, with 209,000 new cases annually. 1 Squamous cell carcinoma is by far the most common histology and each year, there are approximately 170 incident cases in Sweden. 2 In the Nordic countries, the incidence has declined during the last decades along with decreased smoking among men but remains constant for women. 3 , 4
Whereas the survival rate for early‐stage laryngeal squamous cell carcinoma (LSCC) is relatively good (89% overall 5‐year survival for stage I glottic LSCC), 5 advanced disease is associated with poor survival (38% overall 5‐year survival for stage IV glottic LSCC). 5 The survival rate for LSCC has not improved similarly to many other oncologic diseases during the last decades. 2 , 6 For example, in the United States, the 5‐year survival rate for LSCC has decreased from 66% to 63% during the past 40 years. 6
Treatment of laryngeal cancer carries the risk of side effects affecting voice, olfaction and taste. The management protocols thus aim at considering surgical treatment, radiotherapy (RT) or chemoradiotherapy (CRT), either alone or in combination. Early‐stage LSCC (T1‐T2/N0) are often treated with single modality, RT or primary surgery, while the most advanced tumors (T4/N0/N+) often require a combination of surgery, total laryngectomy (TL), with postoperative RT/CRT. Regarding T3 laryngeal cancer, a study in 2003 presented improved locoregional control and larynx preservation with concurrent cisplatin/RT compared with induction chemotherapy or RT alone, which has led to treatment regimens favoring non‐surgical options at many centers. 7 The debate around treatment modality for advanced laryngeal cancer is highly topical. There are several studies that compare primary TL with different larynx preservation methods including CRT, but the results are inconclusive. 8 , 9 , 10 , 11 , 12 , 13 This indicates the need for further research especially regarding the management of advanced laryngeal cancer.
This study presents a retrospective population‐based analysis, with patients identified from the Swedish Head and Neck Cancer Register, of outcome and survival for all patients diagnosed with LSCC in Stockholm County, Sweden between the years 2000 and 2014. Tumor localization, stage, and treatment factors were considered. Our specific aim was to search for subgroups that would warrant further development in the treatment protocol and investigation in future clinical trials.
2. MATERIALS AND METHODS
2.1. Patient data
This was a single‐center cohort study, including all patients diagnosed with laryngeal squamous cell carcinoma in the Stockholm region, Sweden during the time period 2000–2014. In Sweden, all patients regardless of socioeconomic status are diagnosed and treated in public hospitals according to national and hospital guidelines, resulting in a non‐selected cohort. All patients diagnosed with LSCC (C320—malignant neoplasm of the glottis, C321—malignant neoplasm of the supraglottis, C322—malignant neoplasm of the subglottis and C328—malignant neoplasm of overlapping sites of the larynx) were identified from the Swedish Head and Neck Cancer Register, SweHNCR, which has equivalent coverage compared to the national cancer register. Patients treated with palliative intent and a history of previous laryngeal cancer were excluded from further analysis. Clinical data were extracted from the hospital records for the following variables: gender, age, smoking status, date of diagnosis, TNM classification (7th edition), cancer localization, type of treatment, residual tumor after treatment, time to recurrence, localization of recurrence and survival. Treatment was classified as surgery, RT (66–68 Gray) and CRT. All patients had clinical follow‐up visits every 3 months for the first 2 years, and every 6 months for the following 3 years. Residual tumor was calculated as remaining verified cancer within 3 months from end of treatment. The term complete response is used when the patient was considered tumor‐free after primary treatment, that is, had no residual tumor.
2.2. Statistical analysis
The main outcome was overall 5‐year survival (OS), defined as death from any cause within 5 years from diagnosis, calculated from date of diagnosis until date of death or end of study, whichever occurred first. No patients were lost to follow‐up when calculating OS. The secondary outcome was recurrence‐free 5‐year survival (RFS), defined as survival without recurrence within 5 years after last treatment, calculated from date of last treatment until date of recurrence, death (censored), end of study or loss of follow‐up, whichever occurred first. Four patients were lost to follow‐up when calculating RSF since they moved to another region in Sweden. Survival was graphically displayed in Kaplan Meier curves for each outcome, presented overall and stratified by T‐classification. In order to study the prognostic effect of covariates, multivariable Cox proportional hazards models were used to produce hazard ratios (HR) with 95% confidence intervals (95% CI) for each outcome, adjusted for the following prognostic variables (with categorizations in brackets): age (continuous), gender (male or female), T classification (T1, T2, T3 or T4), N classification (N0 or N+), M classification (M0 or M+), transglottic growth (yes or no), tumor site (glottic or supraglottic). The choice to include these variables were decided a priori to the analyses. The proportional hazards assumption was checked by visual inspection of log–log curves and was met for all analyses. All analyses were performed using Stata IC 16.1 (StataCorp).
2.3. Ethics
The study was approved by the Swedish Ethical Review Authority (2019–04829).
3. RESULTS
Completed treatment with curative intent was given to 487/520 (94%) patients (Table 1). The number of deaths during the follow‐up period was 169, which gave an overall median follow up time of 5 years. Five‐year OS and 5‐year RFS for all patients who completed treatment with curative intent are presented stratified by T classification and clinical tumor stage (Tables 2 and 3). OS and RFS stratified by tumor site and T classification for all patients who completed treatment are presented (Figures 1, 2, 3, 4).
TABLE 1.
Baseline characteristics of patients with laryngeal squamous cell carcinoma in Stockholm between 2000–2014 who completed treatment with curative intent.
| LSCC | Glottic | Supraglottic | Subglottic | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| All | All | T1a | T1b | T2 | T3 | T4 | All | T1 | T2 | T3 | T4 | T4 | |
| Number of patients | 487 | 371 | 155 | 25 | 122 | 39 | 30 | 114 | 13 | 43 | 47 | 11 | 2 |
| Age, mean | 66 | 66 | 66 | 63 | 68 | 67 | 64 | 67 | 69 | 67 | 65 | 67 | 70 |
| Gender, female | 75 (15%) | 33 (9%) | 16 (10%) | 5 (20%) | 5 (4%) | 4 (10%) | 3 (10%) | 42 (37%) | 8 (62%) | 17 (40%) | 14 (30%) | 3 (27%) | |
| Gender, male | 412 (85%) | 338 (91%) | 139 (90%) | 20 (80%) | 117 (96%) | 35 (90%) | 27 (90%) | 72 (63%) | 5 (38%) | 26 (60%) | 33 (70%) | 8 (73%) | 2 (100%) |
| Smoking, former or current | 439 (90%) | 327 (88%) | 131 (85%) | 23 (92%) | 107 (88%) | 36 (92%) | 30 (100%) | 110 (96%) | 12 (92%) | 42 (98%) | 45 (96%) | 11 (100%) | 2 (100%) |
| N and M classification | |||||||||||||
| N+ | 62 (13%) | 9 (2%) | 3 (2%) | 2 (5%) | 4 (13%) | 53 (46%) | 2 (15%) | 19 (44%) | 24 (51%) | 8 (73%) | |||
| M+ | 2 (<1%) | 1 (<1%) | 1 (3%) | 1 (<1%) | 1 (2%) | ||||||||
| Primary treatment | |||||||||||||
| RT | 343 (70%) | 274 (74%) | 105 (68%) | 22 (88%) | 119 (98%) | 26 (67%) | 2 (7%) | 69 (61%) | 10 (77%) | 34 (79%) | 22 (47%) | 3 (27%) | |
| CRT | 49 (10%) | 15 (4%) | 1 (4%) | 1 (<1%) | 11 (28%) | 2 (7%) | 34 (30%) | 1 (8%) | 8 (19%) | 24 (51%) | 1 (9%) | ||
| Sx | 56 (11%) | 53 (14%) | 48 (31%) | 1 (4%) | 2 (2%) | 2 (7%) | 3 (3%) | 2 (15%) | 1 (2%) | ||||
| Sx + (C)RT | 39 (8%) | 29 (8%) | 2 (1%) | 1 (4%) | 2 (5%) | 24 (80%) | 8 (7%) | 1 (2%) | 7 (64%) | 2 (100%) | |||
| Outcome | |||||||||||||
| Residual | 40 (8%) | 19 (5%) | 3 (2%) | 2 (8%) | 8 (7%) | 6 (15%) | 21 (18%) | 1 (8%) | 9 (21%) | 10 (21%) | 1 (9%) | ||
| Recurrence | 109 (22%) | 76 (20%) | 21 (14%) | 3 (12%) | 26 (21%) | 20 (51%) | 6 (20%) | 32 (28%) | 4 (31%) | 12 (28%) | 15 (32%) | 1 (9%) | 1 (50%) |
| DOD | 78 (16%) | 47 (13%) | 6 (4%) | 2 (8%) | 18 (15%) | 15 (38%) | 6 (20%) | 30 (26%) | 2 (15%) | 11 (26%) | 15 (32%) | 2 (18%) | 1 (50%) |
Abbreviations: CRT, chemoradiotherapy; DOD, dead of disease; LSCC, laryngeal squamous cell carcinoma; M, distant metastasis; N, regional lymph node metastasis; RT, radiotherapy; Sx, Surgery.
TABLE 2.
Five‐year overall survival (n = 487) and five‐year recurrence‐free survival (n = 469) of all patients with laryngeal squamous cell carcinoma who completed treatment with curative intent stratified by tumor site and T classification.
| All | Glottic | Supraglottic | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Survival, % (CI) | T1a | T1b | T2 | T3 | T4 | T1 | T2 | T3 | T4 | |
| 5‐y OS | 65 (61–69) | 84 (77–89) | 72 (50–86) | 66 (57–74) | 33 (19–48) | 67 (47–80) | 62 (13–82) | 44 (29–58) | 47 (32–60) | 55 (23–78) |
| 5‐y RFS | 78 (73–81) | 90 (84–94) | 91 (69–98) | 77 (68–84) | 47 (30–62) | 80 (61–90) | 64 (30–85) | 66 (49–79) | 64 (47–77) | 86 (33–98) |
Abbreviations: 5‐y, five‐year; CI, confidence interval; OS, overall survival; RFS, recurrence‐free survival.
TABLE 3.
Five‐year overall survival (n = 487) and five‐year recurrence‐free survival (n = 469) stratified by clinical tumor stage for all patients with laryngeal squamous cell carcinoma who completed treatment with curative intent.
| Laryngeal squamous cell carcinoma | ||||
|---|---|---|---|---|
| Survival, % (CI) | Stage I | Stage II | Stage III | Stage IV |
| No. of patients | 193 | 140 | 79 | 75 |
| 5‐y OS | 81 (75–86) | 63 (54–70) | 43 (32–54) | 53 (41–64) |
| No. of patients | 192 | 135 | 77 | 65 |
| 5‐y RFS | 89 (83–92) | 77 (68–83) | 54 (41–64) | 75 (62–84) |
Abbreviations: 5‐y, five‐year; CI, confidence interval; OS, overall survival; RFS, recurrence‐free survival.
FIGURE 1.
Overall survival of all patients with laryngeal squamous cell carcinoma treated with curative intent stratified by tumor site (n = 487).
FIGURE 2.
Recurrence‐free survival of all patients with laryngeal squamous cell carcinoma treated with curative intent stratified by tumor site (n = 469).
FIGURE 3.
Overall survival of all patients with laryngeal squamous cell carcinoma treated with curative intent stratified by T‐classification (n = 487).
FIGURE 4.
Recurrence‐free survival of all patients with laryngeal squamous cell carcinoma treated with curative intent stratified by T‐classification (n = 469).
3.1. T1 glottic LSCC
RT was given to 128/180 (71%) of the patients with T1 glottic LSCC and 125/128 (98%) had complete response. Recurrence was diagnosed in 14/128 (11%) of these patients, and 13 underwent TL.
Surgery was performed on 49/180 (27%) of the patients with T1 glottic LSCC, of whom 19/49 (39%) were operated with microscopic laser surgery (MLS) and 30/49 (61%) underwent resection with cold instruments. Complete response was observed in 47/49 (96%). Recurrence was diagnosed in 9/49 (18%) of the patients treated with surgery as primary treatment. Two of these patients needed salvage TL after first being treated with RT.
The OS for patients with T1 LSCC treated with RT versus surgery as the primary treatment was 80% (73–86) versus 82% (69–90), respectively.
3.2. T1 supraglottic LSCC
Of the patients with T1 supraglottic LSCC 11/13 (85%) were primarily treated with RT (or CRT). Complete response was observed in 10/11 (91%) of the patients and 2/11 (18%) presented with a recurrence.
The two (15%) remaining patients with T1 supraglottic LSCC were treated with MLS, one with additional staging neck dissection. Both patients (100%) had a recurrence.
3.3. T2 glottic LSCC
The vast majority, that is, 120/122 (98%) of the patients with T2 glottic LSCC were primarily treated with RT (one with CRT) and 109/120 (91%) had a complete response. Recurrence was diagnosed in 26/120 (22%) of the patients out of which 19 were operated with TL.
3.4. T2 supraglottic LSCC
Among 43 patients, 42 patients with T2 supraglottic LSCC were primarily treated with RT 34 or CRT 8 of which 18/42 (43%) were operated with adjuvant neck dissection and 33/42 (79%) had a complete response. Recurrence was diagnosed in 10/34 (29%) of the patients treated with RT and in 1/8 (13%) of the patients treated with CRT. Eight of these patients were operated with TL with or without neck dissection.
3.5. T3 glottic LSCC
RT was given to 26/39 (67%) of the patients with T3 glottic LSCC. Complete response was observed in 21/26 (81%) of the patients and 14/26 (54%) presented with a recurrence (75% local). Eight of these patients underwent TL.
CRT was given to 11/39 (28%). Adjuvant neck dissection was performed on two patients. Complete response was observed in 10/11 (91%) of the patients and 6/11 (55%) presented with a recurrence (83% local). Four of them underwent TL.
3.6. T3 supraglottic LSCC
RT only was given to 22/47 (47%) of the patients with T3 supraglottic LSCC, three patients also had a neck dissection. Complete response was observed in 15/22 (68%) of the patients and 5/22 (23%) presented with a recurrence.
CRT was given to 24/47 (51%) of the patients with T3 supraglottic LSCC. Additional neck dissection was performed on three patients. Complete response was observed in 19/24 (79%) of the patients and 10/24 (42%) presented with recurrence (80% local). Seven of the patients with recurrence underwent TL.
3.7. T4 glottic LSCC
RT or CRT only was given to 4/30 (13%) of the patients as primary treatment. There was no sign of recurrence during follow‐up. The majority, 21/30 (70%) underwent TL (five patients in combination with neck dissection) and 19 of those patients had postoperative RT. Recurrence was diagnosed in 5/21 (24%) of the patients in this group and they all had palliative treatment. TL and postoperative CRT was given to 5/30 (17%) of the patients with T4 glottic LSCC where one out of five patients had residual tumor and were then treated with palliative intent.
All of the 30 (100%) patients who presented with T4 glottic LSCC had a complete response.
3.8. T4 supraglottic LSCC
RT or CRT only was given to 4/11 (36%) of the patients due to comorbidity. Two of these patients were considered free from disease after treatment. Seven patients (64%) went through TL (five in combination with neck dissection) and postoperative RT or CRT. One of the patients treated with postoperative RT presented with a regional recurrence and finally died from disease. Complete response was observed in 82% of the 11 patients with T4 supraglottic LSCC.
3.9. Survival for patients with T3, T4 LSCC
In the present cohort patients with T4 laryngeal cancer had significantly better survival compared with those with a class T3 tumor. The biggest difference was observed in the glottic group. The 5‐year OS and RFS for the patients with T3 glottic LSCC was 33% and 47%, respectively. Of note, the patients with T4 glottic LSCC, having typically been treated with TL and postoperative RT/CRT, had OS 67% and RFS 80%. In the group with supraglottic LSCC, there was not as big a difference but even here patients with T4 tumors had better survival. OS and RSF were 47% and 64% in the T3 group compared with 55% and 86% in the T4 group. The relatively poor survival for T3 tumors remained after adjustment in the multivariable analyses (Table 4). Poorer prognosis was also associated with increased age (5% per year), male gender, lymph node metastasis (N+), distant metastasis (M+), transglottic tumor growth and supraglottic LSCC.
TABLE 4.
Hazard ratios (HR) with 95% confidence levels (95% CI) for 5‐year overall survival (5‐y OS) and 5‐year recurrence‐free survival (5‐y RSF) across seven prognostic variables.
| 5‐y OS | 5‐y RFS | |
|---|---|---|
| HR (95% CI) | HR (95% CI) | |
| Age (continuous) | 1.05 (1.03–1.06) | 0.99 (0.98–1.01) |
| Gender | ||
| Male | 1.00 (ref) | 1.00 (ref) |
| Female | 0.67 (0.43–1.05) | 0.47 (0.24–0.93) |
| T classification | ||
| T1 | 1.00 (ref) | 1.00 (ref) |
| T2 | 1.92 (1.25–2.94) | 2.10 (1.19–3.69) |
| T3 | 2.96 (1.77–4.94) | 3.73 (1.89–7.36) |
| T4 | 1.42 (0.68–2.97) | 1.07 (0.39–2.96) |
| N classification | ||
| N0 | 1.00 (ref) | 1.00 (ref) |
| N+ | 1.36 (0.83–2.23) | 1.16 (0.59–2.39) |
| M classification | ||
| M0 | 1.00 (ref) | N/A a |
| M+ | 1.56 (0.20–12.11) | N/A a |
| Transglottic | ||
| No | 1.00 (ref) | 1.00 (ref) |
| Yes | 1.49 (0.95–2.36) | 1.76 (1.00–3.09) |
| Tumor site | ||
| Glottic | 1.00 (ref) | 1.00 (ref) |
| Supra glottic | 1.60 (1.02–2.50) | 1.38 (0.77–2.48) |
Too few patients for output.
3.10. Subglottic LSCC
Two patients (2/487) presented with subglottic LSCC, both (100%) classified as T4. Both patients went through TL and postoperative RT. One patient (50%) had a complete response and one (50%) presented with recurrence and got palliative treatment.
4. DISCUSSION
This retrospective single‐center cohort study found an unexpectedly poor survival for patients with T3 glottic laryngeal cancer, with a significantly poorer prognosis compared with patients with a T4 tumor. The poor survival for the T3 group persisted after adjustment in multivariate analysis. Regarding supraglottic LSCC, the T classification of the primary tumor did not appear to have a significant impact on observed survival, which in general was poorer compared with glottic LSCC.
Previous studies with large series show that laryngeal preservation treatment with CRT, has an equivalent survival compared to the neoadjuvant TL for patients with T3 LSCC as primary treatment. 14 , 15 , 16 There are also other organ preservation strategies such as open partial laryngectomies or transoral laser microsurgery with similar survival 17 , 18 that we do not discuss in this study as it is not part of our treatment protocol. However, the majority of previous studies have regarded laryngeal cancer as a single entity, without dividing their series into glottic and supraglottic cancer. In addition, the study design in earlier studies differs much which makes it difficult to conduct meta‐analyses and draw conclusions and ultimately adjust for the treatment regimen. 18 We can only state at this point that the present results in this study suggest that primary TL with adjuvant RT/CRT provides improved survival for patients with advanced LSCC. However, only 41% of the patients with T3 LSCC were treated with CRT as this method was used sparingly in the first 5 years covered by the study.
The management guidelines for laryngeal cancer are rather similar internationally, 19 , 20 however, cancer centers tend to have different traditions regarding the primary treatment modality. In some centers, it is more common with surgery as the first option for T1 and selected T2 tumors while other centers often choose RT as the first modality. If we look at the outcome and OS for the whole group it is similar in the Nordic countries and in the United States and it has not changed remarkably during the last decade. 6 , 21 However, it is important to emphasize the well‐known differences between glottic and supraglottic LSCC and in many respects, these two cancers have completely different characteristics. In our cohort, the glottic LSCC mainly affected men (91%) and the majority were diagnosed in an early stage (79% in stage I or II) where only 2.6% presented lymph node metastasis at the time of diagnosis. Supraglottic LSCC on the other hand is a much smaller group of patients of which 36% were women. Seventy‐two percent were diagnosed with stage III–IV disease and 50% had lymph node metastasis at diagnosis. Furthermore, the pattern of survival between glottic and supraglottic laryngeal cancer differs in the present and previous reports, 22 and the differences should be taken under consideration when planning the treatment of these patients. Nevertheless, it can be difficult to assess the site of origin in two adjacent structures, especially in the more advanced tumors (T3 and T4). However, our data on glottic and supraglottic LSCC show different outcomes and different cervical neck node positivity implying a true difference.
The treatment strategy for LSCC has not changed drastically in Stockholm during the 15 years covered by the present study, but some developments have occurred. The oncologic treatment in general consists of unchanged fractionated RT in combination with concomitant chemotherapy with cisplatin for the advanced stages. Cetuximab will be given if cisplatin is contraindicated. 23 , 24 CRT was however, used sparingly for the first 5 years of our study and therefore likely contributed to the large difference in survival between T3 and T4 LSCC. While the surgical strategy for the advanced stages has remained unchanged, surgery has been more frequently offered as primary treatment for patients with early‐stage LSCC in many centers including Karolinska University Hospital. 25 Here, surgery as primary treatment for patients with T1a glottic LSCC was performed in 24% of the patients during 2000–2004 compared with 40% during 2010–2015. Our and other studies show similar results in survival regardless of single treatment modality for patients with T1 glottic LSCC. 26 , 27 , 28 In the case of recurrent T1 disease, it could be beneficial to have surgery as the primary treatment since RT/CRT then still remains a treatment option and TL could be avoided. In either case, it is of paramount importance to select an appropriate modality at a multidisciplinary tumor board meeting depending on the patient and tumor characteristics.
Regarding the T1b group with tumor extension on both vocal cords, patients were mainly treated with RT to avoid anterior commissure web formation, a well‐known complication after surgery. In this study, we did not evaluate voice quality and complications after surgery/RT in this group of patients. Other studies however indicate that with small tumors, surgery is likely to be equivalent to RT regarding voice function after treatment. 29 The survival outcome for T1 glottic laryngeal cancer is in general favorable and our results compare well with results from other studies. 5 , 30
Although previous studies show equivalent outcomes for surgery and RT alone for selected T2 tumors, 15 we can establish that surgery as a single primary treatment modality was used sparingly for T2 tumors in this study. Only two patients out of 122 were treated with surgery as the primary treatment. This is probably tradition related at our center but does not seem to have had a negative impact on the outcome in general. 31
In our study almost all patients with supraglottic LSCC were treated with RT, as single modality (T1‐, T2‐disease) or combined with chemotherapy (T3‐disease) or TL (T4‐disease). Only 3/114 patients were treated with surgery alone. The patients with supraglottic LSCC have poor prognosis in general and in this study, T class did not seem to have a major impact on survival since outcomes are almost similar for T1‐T3 disease with 64%–66% 5‐year RFS. Interestingly patients with T4 disease showed improved RFS (84%). The patients diagnosed with T1 and T4 supraglottic LSCC are relatively few in our cohort and thus, no definitive conclusions can be drawn, but the slightly better survival among patients with a T4 tumor compared with those with a T1‐T3 tumor may suggest an advantage of combined treatment approach for patients with supraglottic LSCC. The majority of patients with supraglottic LSCC present N+ disease at the time of diagnosis, which probably is an important negative prognostic factor. Few studies separate the survival for different T classifications regarding supraglottic LSCC, though the treatment in our cohort is consistent with previously published data, although the survival rates differ with improved survival for patients with T2 disease in our cohort. 5
A total of 122 TLs were performed in this series comprising 487 LSCC patients treated with the intention to cure. In 39 cases, almost exclusively on T4 LSCC, TL was the primary treatment, usually in combination with postoperative RT or CRT. TL was chosen as the primary treatment for patients with T3 glottic and supraglottic LSCC in 5% and 2%, respectively. Consequently, in the majority of the patients, TL was used as salvage surgery, and here performed on 83 (68%) patients with local/loco‐regional residual or recurrence. Even though TL is a well‐proven treatment against persistent and recurrent disease when first treated with organ preservation therapy 32 it has been shown to contribute to higher risk of surgical complications compared to primary TL. 33 Although oncological organ preservation strategies have an important role in the treatment of advanced laryngeal cancer 9 , 11 , 34 this study with better survival for patients with T4 compared with T3 glottic LSCC shows that TL provides an effective treatment regime. At the same time, it is mutilating surgery with lifelong consequences for the patient. Finding markers for selecting patients with advanced tumors that respond poorly to RT and who would benefit from primary surgery would most likely improve the survival of patients with T3 LSCC.
Since the study is single‐center, the external validity decreases compared to multicentre studies. Even though the present study is a retrospective analysis, the cohort is relatively large and population‐based. Since all patients diagnosed with LSCC in Stockholm during the time period were included and almost all with a complete follow‐up the risk of selection bias was reduced. The data were prospectively collected from medical records with a long follow‐up. Unfortunately, information about the WHO status and comorbidity of these patients was not available. It is important to compare the often troublesome and lifelong side effects of both surgery and RT when we compare the treatment of LSCC, something we did not do in this study. Furthermore, since the patient cohort covers a long period, minor changes in treatment regimes have occurred. Also, the TNM staging system was changed regarding cartilage invasion in 2003, which may have contributed to the fact that a few patients with T4 tumors would today be classified as T3. 35 , 36 We have not adjusted data for changes in treatment regimes over time with a risk of bias by confounding, however, at our center, treatment has been consistent within and between the different subsites in larynx and T classification implicating accuracy in the results.
5. CONCLUSION
The present treatment results compare well with previous reports regarding T1 and T2 LSCC. However, T3 glottic laryngeal SCC was mainly treated with RT/CRT and resulted in an unexpectedly poor survival, especially when compared with the more advanced tumors (T4) where the majority were treated with primary TL and adjuvant RT resulting in better 5‐year OS and RFS.
FUNDING INFORMATION
Karolinska University Hospital, Laryngeal foundation, Stiftelsen Acta Oto‐Laryngologica, Swedish Association for Otorhinolaryngology Head and Neck Surgery.
CONFLICT OF INTEREST STATEMENT
Eivind Gottlieb‐Vedi declares employment at Sanofi.
Blomkvist R, Marklund L, Hammarstedt‐Nordenvall L, Gottlieb‐Vedi E, Mäkitie A, Palmgren B. Treatment and outcome among patients with laryngeal squamous cell carcinoma in Stockholm—A population‐based study. Laryngoscope Investigative Otolaryngology. 2023;8(2):441‐449. doi: 10.1002/lio2.1034
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