- Email: [email protected]
Survival Rates After Surgical or Non-surgical Treatment for Advanced Resectable Squamous Cell Carcinoma of the Oral Cavity and Oropharynx
Survival for Resectable Asian J Oral MaxillofacOral SurgCancer 2003;15:96-100. CLINICAL OBSERVATIONS
Survival Rates After Surgical or Non-surgical Treatment for Advanced Resectable Squamous Cell Carcinoma of the Oral Cavity and Oropharynx Hiroshi Kurita,1 Hiroichi Kobayashi,1 Takeshi Koike,1 Shigeru Fujimori,1 Kenji Kurashina,1 Naoto Shikama2 1 Department of Dentistry and Oral Surgery, and 2Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
Abstract Objective: To determine the difference in survival rates between surgical and non-surgical treatment for resectable squamous cell carcinoma of the oral cavity and oropharynx. Patients and Methods: A retrospective chart review of 53 patients in a single institution who preferred surgical treatment and 11 patients who preferred non-surgical treatment. Results: The overall survival probability rate of the surgically-treated patients was 90% at 1 year, 76% at 2 years, and 61% at 5 years, while that of the non-surgically–treated patients was 60%, 30%, and 15%, respectively. The difference in the cause-specific survival rate between the 2 groups was significant (logrank test, p < 0.05). There were significant differences in the distribution of patient’s age, T-stage, N-stage, and performance status. However, the Cox multivariate analysis revealed that the treatment was a significant independent predictor. Conclusions: The results suggest that when non-surgical treatment is given for resectable cancer, the probability of survival from the disease is 30% and death would occur within 2 years. The survival rate is half that of those who undergo radical surgery (67%). Key Words: Oral cancer, Surgery, Survival
Introduction Oral cancer (usually squamous cell carcinoma; SCC) is a serious problem, especially for patients in whom the disease is at an advanced stage. In the Department of Dentistry and Oral Surgery at the Shinshu University Hospital in Japan, most patients with advanced oral cancer are primarily treated with surgery combined with radiotherapy. Recent surgical advances enable surgeons to perform a radical and wide resection of the tumour, which is associated with an improved prognosis.1,2 However, despite the surgical advances, patients may have partial or total disfigurement and loss of Correspondence: Hiroshi Kurita, Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. Tel: (81 0263) 372 677, Fax: (81 0263) 372 676 E-mail: [email protected]
96
stomatognathic functions as a result of the surgery.3,4 With increasing interest in health-related quality of life, some patients opt for organ preservation and select a non-surgical treatment (radiotherapy and/ or chemotherapy) instead of radical surgery. On condition that the oncological outcome is similar, the strategy that produces better functional outcome would be preferred. Considerable efforts to improve the effect of chemotherapy and/or radiotherapy have been made and several researchers have reported a good survival rate that may be comparable with that of primary surgical treatment.5-7 Unfortunately, however, no nonsurgical regimen has been shown to be an alternative to primary surgical treatment as there is no definitive proof that non-surgical treatments surpass surgical treatment. In these circumstances, oral oncologists need to discuss the treatment alternatives with reference to survival rates as well as quality of life. Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurita, Kobayashi, Koike, et al
To date, there has been no study comparing the survival rates of patients who received primary surgical treatment with that of patients who received non-surgical treatment in a single institution. The aim of this retrospective study was to define the difference in survival rates for patients who underwent radical surgery and for those who underwent non-surgical treatment for resectable SCC of the oral cavity and oropharynx.
Patients and Methods The tumour registry at the Department of Dentistry and Oral Surgery in Shinshu University Hospital listed 64 patients who presented with previously untreated advanced SCC (stage III and IV) in the oral cavity or oropharynx from 1985 to 1997. There were 26 women and 38 men, with an age range from 39 to 87 years (median, 65 years). This list did not include patients who subsequently underwent no treatment or palliative treatment. No patients had distant metastases at the beginning of treatment. The standard treatment for advanced oral tumours in the Department of Dentistry and Oral Surgery is surgical composite resection combined with radiation therapy (surgical treatment). Primary radiation therapy, with or without chemotherapy, is also used to control the tumour (non-surgical treatment). Patients are informed of the proposed treatment strategies (surgical or non-surgical treatment) with thorough explanations of the tumour stage, treatment modalities, complications, and prognosis. Fifty three patients selected surgical treatment and underwent radical resection of the primary tumour with therapeutic or elective radical neck dissections following preoperative radiation therapy (a total dose of 30 Gy to 40 Gy delivered in 1.8 Gy or 2.0 Gy fractions during 3 to 4 weeks) alone or combined with chemotherapy. Eight patients received additional postoperative irradiation. Twenty eight patients received postoperative adjuvant chemotherapy (daily oral administration of 5-fluorouracil [5-FU] for up to 2 years). Eleven patients preferred organ preservation and selected non-surgical treatment. These patients underwent radiation therapy (a total dose of 49 Gy Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
to 76 Gy delivered in 1.8 Gy or 2.0 Gy fractions for 6 to 9 weeks) given with or without concurrent chemotherapy (daily administration of 5-FU or low dose cisplatin). One patient underwent debulking surgery and another 2 patients received neoadjuvant chemotherapy (intravenous cisplatin 50 mg/m2 and intramuscular peplomycin 25 mg/body). All records were reviewed to ascertain the patient’s age, sex, Eastern Cooperative Oncology Group performance status,8 primary site, and tumour stage according to the TNM clinical staging system proposed by the International Union Against Cancer.9 All patients were followed up on a regular basis — every 2 weeks for the first year, every month for the second year, every 3 months for the third and fourth years, and then biannually for life. The median follow up period was 28 months (range, 1 to 153 months). Survival calculations were determined by the Kaplan-Meier actuarial method. Deaths from any cause were considered uncensored observations for overall survival analysis, while deaths from the tumours were considered uncensored observations for cause-specific survival analysis. The log-rank test was used to test for differences between actual curves. For nominal data, Fisher’s exact probability test or goodness test of fit for chi-square was used, and Mann-Whitney U-test was used for numerical data. The Cox proportional hazards model was used to analyse the influence of multiple variables on survival. Analyses were performed using the StatView, software package for Macintosh (SAS Institute, Inc., Cary, USA). All p values less than 0.05 were considered to indicate statistical significance.
Results A comparison of clinical data between the patients who underwent appropriate radical combined treatment including surgery and those who underwent non-surgical treatment is shown in Table 1. None of the patients had distant metastasis at the start of treatment. There were statistically significant differences in patient’s age, T stage, N stage, and performance status between the groups. The patients who underwent non-surgical treatment were older, and had more advanced T and N stages, and had more severe performance status (Mann-Whitney U-test, 97
Survival for Resectable Oral Cancer
p < 0.05). On the other hand, there was no significant difference as to distribution of sex and primary tumour or clinical stage.
100 90 80 70 Survival (%)
The overall survival curve is shown in Figure 1. The overall survival probability rate of the surgicallytreated patients was 90% at 1 year, 76% at 2 years, and 61% at 5 years, while that of the non-surgically treated patients was 60%, 30%, and 15%, respectively. Among the non-surgically–treated patients, 5 died as a result of the tumour and 2 died of other disease (at 26 and 81 months) without clinical evidence of the tumour. The cause-specific survival curves are shown in Figure 2. The cause-specific survival probability of the surgically-treated patients was 90% at 1 year, 76% at 2 years, and 66% at 5 years (disease-free survival [DFS] was 64%). That of the non-surgically–treated patients was 60%, 30%,
60
Surgical treatment group
50 40 30 20
Non-surgical treatment group
10 0
20
40
60 80 100 Time (months)
140
160
Figure 1. Comparison of overall survival between the surgical treatment group (n = 53) and the non-surgical treatment group (n = 11). The survival rate of the surgical treatment group is significantly higher than that of the nonsurgical treatment group (log-rank test, p < 0.05).
Surgical treatment
No surgical treatment
Sex Female Male
23 (36%) 30 (47%)
3 (5%) 8 (12%)
Age (years) Median Range
64 39-83
75 49-87
p Value NS*
<0.05†
Primary site Tongue Lower gum Others Buccal mucosa Upper gum Floor of the mouth Oropharynx
20 15 18 8 4 5 1
1 6 4 1 0 1 2
T stage 2 3 4
13 17 23
0 1 10
N stage 0 1 2 3
14 14 25 0
1 1 8 1
Clinical stage III IV
17 36
1 10
Performance status 0 1 2 3
120
NS‡
<0.01†
<0.05†
NS*
<0.01† 36 13 2 2
3 4 2 2
Abbreviations: NS = no statistically significant difference. * Fisher’s exact probability test. † Mann-Whitney U-test ‡ Goodness test of fit for chi-square Table 1. Comparison of clinical data between the surgical treatment group and non-surgical treatment group.
98
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurita, Kobayashi, Koike, et al
methods for advanced but resectable oral carcinoma compared with those who were treated by primary radical resection with appropriate adjuvant therapy.
100 90 80 Survival (%)
70
Surgical treatment group
60 50 40 30
Non-surgical treatment group
20 10 0
20
40
60 80 100 Time (months)
120
140
160
Figure 2. Comparison of cause-specific survival between the surgical treatment group (n = 53) and the non-surgical treatment group (n = 11). The survival rate of the surgical treatment group is significantly higher than that of the nonsurgical treatment group (log-rank test, p < 0.05).
and 30% (DFS, 18%), respectively. The median survival (Kaplan-Meier estimate) for the non-surgically treated patients was 12 months (cumulative proportion of survival at 8 months was 0.550). In both survival curves, the rate for the surgically-treated patients was significantly higher than that for the nonsurgically–treated patients (log-rank test, p < 0.05). Results from the survival analysis using the Cox proportional hazard model showed that the choice of treatment was a significant independent predictor for overall survival, while other factors had no influence on the survival (Table 2).
Discussion The purpose of this study was to estimate the probability of survival of patients treated by non-surgical Variables
Regression coefficient (± SE)
Relative risk
p Value
Treatment option Age (years) T stage N stage Performance status
-1.170 ± 0.509
0.310
0.02
0.012 ± 0.021 0.067 ± 0.290 0.197 ± 0.143 0.354 ± 0.254
1.012 1.069 1.218 1.425
0.58 0.82 0.17 0.16
Table 2. Multivariate analysis of the relationship between prognostic variables and overall survival using the Cox proportional hazard model.
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
The results of this study showed that the prognosis of the non-surgically–treated patients was poor. In the analysis of the cause-specific survival, the survival curve of the surgical therapy group showed a steady decrease during the first 33 months and became steady at 66%. There was a sharp decrease in the survival rate of the non-surgically–treated patients during the first 15 months, and the rate became steady at 30%. These data showed that for non-surgical treatments, the probability of survival from the disease was 30% and death would occur within 2 years. The rate was half that for patients who underwent radical surgery (67%). Recently, feasibility trials of chemoradiotherapy have received much attention. Some researchers used chemotherapy with concomitant radiation for advanced head and neck cancer and reported improved survival rates of 40% at 2 years,10 51% at 3 years,11 and 43% at 5 years.12 Some researchers used alternating chemotherapy and radiotherapy and reported better survival rates of 41% at 3 years5 and 67% at 5 years.13 In addition, several studies on the improvement of radiation therapy have been performed, including accelerated radiation treatment with or without concomitant boost.14,15 If the oncological effect were similar, these non-surgical treatments would replace primary surgery. It is recognised that there might be a selection bias in this study, in that the patients with older age, advanced cancer, or poor performance status selected the non-surgical treatments. No patient died of concurrent disease in the non-surgical treatment group. There were statistically significant differences in the distribution of patient’s age, T and N stage, and performance status between the groups. This result suggests that patients whose carcinomas were more advanced or who were older might have selected the non-surgical treatment. However, results from the survival analysis using the Cox proportional hazard model revealed that the option of treatment was a significant independent predictor for overall survival. 99
Survival for Resectable Oral Cancer
As a result of this retrospective study, it is possible to reconfirm the significant difference in the survival rate between surgical and non-surgical treatments in patients with advanced but resectable oral/oropharyneal cancer. Radical surgery may physically and mentally debilitate a patient, and patients may therefore be inclined to select non-surgical treatment. However, it is clear that non-surgical treatments are inferior to surgical treatments when it comes to survival. Currently, it is possible only to clearly inform patients about treatment modalities and their complications and prognoses, and allow them to make an informed decision when selecting treatment options.
References 1. Million RR, Cassisi NJ, editors. Management of head and neck cancer: a multidisciplinary approach. Philadelphia: Lippincott; 1994. 2. Franceschi D, Gupta R, Spiro RH, Shah JP. Improved survival in the treatment of squamous cell carcinoma of the oral tongue. Am J Surg 1993; s166:360-365. 3. Teichgraeber J, Bowman J, Geopfert H. New test series for the functional evaluation of oral cavity cancer. Head Neck Surg 1985;8:9-20. 4. Harrison JB, Zelefsky MJ, Armstrong JG, Capper E, Gaynor JJ, Sessions RB. Performance status after treatment for squamous cell cancer of the base of the tongue — comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 1994;30;953-957. 5. Merlano M, Vitale V, Rosso R, Benasso M, Corvo R, Cavallari M, Sanguineti G, Bacigalupo A, Badellino F, Margarino G, Brema F, Pastorino G, Marziano G, Grimaldi A, Scasso F, Sperati G, Pallestrini E, Garaventa G, Accomando E, Cordone G, Comella, G, Daponte A, Rubagotti A, Bruzzi P, Santi L. Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med 1992;327:1115-1121. 6. Adelstein DJ, Sharan VM, Damm C, Earle AS, Shah AC, Haria CD, Trey JE, Carter SG, Hines JD. Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative,
100
squamous cell head and neck cancer. Results and surgical implications. Cancer 1992;70: 2685-2690. 7. Khan A, Spiro JD, Dowsett R, Greenberg BR. Sequential chemotherapy and radiotherapy for organ preservation in advanced resectable nonlaryngeal head and neck cancer. Am J Clin Oncol 1999;22:403-407. 8. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, Carbone PP. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655. 9. Sobin LH, Wittenkind CH, editors. TNM classification of malignant tumors. 5th ed. New York: John Wiley & Sons, Inc; 1997:17-42. 10. Macmillan CH, Carrick K, Bradley PJ, Morgan DA. Concomitant chemo/radiotherapy for advanced carcinoma of the head and neck. Br J Radiol 1991;64:941-946. 11. Calais G, Alfonsi M, Bardet E, Sire C, Germain T, Bergerot P, Rhein B, Tortochaux J, Oudinot P, Bertrand P. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma. J Natl Cancer Inst 1999;91:2081-2086. 12. Taylor SG 4th, Murthy Ak, Griem KL, Recine DC, Kiel K, Blendowski C, Hurst PB, Showel JT, Hutchinson JC Jr, Campanella RS, Chen S, Caldarelli DD. Concomitant cisplatin/5-FU infusion and radiotherapy in advanced head and neck cancer: 8-year analysis of results. Head Neck 1997;19:684-691. 13. Zidan J, Kuten A, Rosenblatt E, Robinson E. Intensive chemotherapy using cisplatin and fluorouracil followed by radiotherapy in advance head and neck cancer. Oral Oncol 1997;33:129-135. 14. MacKenzie R, Balogh J, Choo R, Franssen E. Accelerated radiotherapy with delayed concomitant boost in locally advanced squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 1999;45:589-595. 15. Lamb DS, Denham JW, Morum PE, Gray AJ. Long-term results of accelerated radiation treatment for advanced head and neck cancer. Radiother Oncol 1998;49:29-32.
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Survival Rates After Surgical or Non-surgical Treatment for Advanced Resectable Squamous Cell Carcinoma of the Oral Cavity and Oropharynx Hiroshi Kurita,1 Hiroichi Kobayashi,1 Takeshi Koike,1 Shigeru Fujimori,1 Kenji Kurashina,1 Naoto Shikama2 1 Department of Dentistry and Oral Surgery, and 2Department of Radiology, Shinshu University School of Medicine, Matsumoto, Japan
Abstract Objective: To determine the difference in survival rates between surgical and non-surgical treatment for resectable squamous cell carcinoma of the oral cavity and oropharynx. Patients and Methods: A retrospective chart review of 53 patients in a single institution who preferred surgical treatment and 11 patients who preferred non-surgical treatment. Results: The overall survival probability rate of the surgically-treated patients was 90% at 1 year, 76% at 2 years, and 61% at 5 years, while that of the non-surgically–treated patients was 60%, 30%, and 15%, respectively. The difference in the cause-specific survival rate between the 2 groups was significant (logrank test, p < 0.05). There were significant differences in the distribution of patient’s age, T-stage, N-stage, and performance status. However, the Cox multivariate analysis revealed that the treatment was a significant independent predictor. Conclusions: The results suggest that when non-surgical treatment is given for resectable cancer, the probability of survival from the disease is 30% and death would occur within 2 years. The survival rate is half that of those who undergo radical surgery (67%). Key Words: Oral cancer, Surgery, Survival
Introduction Oral cancer (usually squamous cell carcinoma; SCC) is a serious problem, especially for patients in whom the disease is at an advanced stage. In the Department of Dentistry and Oral Surgery at the Shinshu University Hospital in Japan, most patients with advanced oral cancer are primarily treated with surgery combined with radiotherapy. Recent surgical advances enable surgeons to perform a radical and wide resection of the tumour, which is associated with an improved prognosis.1,2 However, despite the surgical advances, patients may have partial or total disfigurement and loss of Correspondence: Hiroshi Kurita, Department of Dentistry and Oral Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. Tel: (81 0263) 372 677, Fax: (81 0263) 372 676 E-mail: [email protected]
96
stomatognathic functions as a result of the surgery.3,4 With increasing interest in health-related quality of life, some patients opt for organ preservation and select a non-surgical treatment (radiotherapy and/ or chemotherapy) instead of radical surgery. On condition that the oncological outcome is similar, the strategy that produces better functional outcome would be preferred. Considerable efforts to improve the effect of chemotherapy and/or radiotherapy have been made and several researchers have reported a good survival rate that may be comparable with that of primary surgical treatment.5-7 Unfortunately, however, no nonsurgical regimen has been shown to be an alternative to primary surgical treatment as there is no definitive proof that non-surgical treatments surpass surgical treatment. In these circumstances, oral oncologists need to discuss the treatment alternatives with reference to survival rates as well as quality of life. Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurita, Kobayashi, Koike, et al
To date, there has been no study comparing the survival rates of patients who received primary surgical treatment with that of patients who received non-surgical treatment in a single institution. The aim of this retrospective study was to define the difference in survival rates for patients who underwent radical surgery and for those who underwent non-surgical treatment for resectable SCC of the oral cavity and oropharynx.
Patients and Methods The tumour registry at the Department of Dentistry and Oral Surgery in Shinshu University Hospital listed 64 patients who presented with previously untreated advanced SCC (stage III and IV) in the oral cavity or oropharynx from 1985 to 1997. There were 26 women and 38 men, with an age range from 39 to 87 years (median, 65 years). This list did not include patients who subsequently underwent no treatment or palliative treatment. No patients had distant metastases at the beginning of treatment. The standard treatment for advanced oral tumours in the Department of Dentistry and Oral Surgery is surgical composite resection combined with radiation therapy (surgical treatment). Primary radiation therapy, with or without chemotherapy, is also used to control the tumour (non-surgical treatment). Patients are informed of the proposed treatment strategies (surgical or non-surgical treatment) with thorough explanations of the tumour stage, treatment modalities, complications, and prognosis. Fifty three patients selected surgical treatment and underwent radical resection of the primary tumour with therapeutic or elective radical neck dissections following preoperative radiation therapy (a total dose of 30 Gy to 40 Gy delivered in 1.8 Gy or 2.0 Gy fractions during 3 to 4 weeks) alone or combined with chemotherapy. Eight patients received additional postoperative irradiation. Twenty eight patients received postoperative adjuvant chemotherapy (daily oral administration of 5-fluorouracil [5-FU] for up to 2 years). Eleven patients preferred organ preservation and selected non-surgical treatment. These patients underwent radiation therapy (a total dose of 49 Gy Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
to 76 Gy delivered in 1.8 Gy or 2.0 Gy fractions for 6 to 9 weeks) given with or without concurrent chemotherapy (daily administration of 5-FU or low dose cisplatin). One patient underwent debulking surgery and another 2 patients received neoadjuvant chemotherapy (intravenous cisplatin 50 mg/m2 and intramuscular peplomycin 25 mg/body). All records were reviewed to ascertain the patient’s age, sex, Eastern Cooperative Oncology Group performance status,8 primary site, and tumour stage according to the TNM clinical staging system proposed by the International Union Against Cancer.9 All patients were followed up on a regular basis — every 2 weeks for the first year, every month for the second year, every 3 months for the third and fourth years, and then biannually for life. The median follow up period was 28 months (range, 1 to 153 months). Survival calculations were determined by the Kaplan-Meier actuarial method. Deaths from any cause were considered uncensored observations for overall survival analysis, while deaths from the tumours were considered uncensored observations for cause-specific survival analysis. The log-rank test was used to test for differences between actual curves. For nominal data, Fisher’s exact probability test or goodness test of fit for chi-square was used, and Mann-Whitney U-test was used for numerical data. The Cox proportional hazards model was used to analyse the influence of multiple variables on survival. Analyses were performed using the StatView, software package for Macintosh (SAS Institute, Inc., Cary, USA). All p values less than 0.05 were considered to indicate statistical significance.
Results A comparison of clinical data between the patients who underwent appropriate radical combined treatment including surgery and those who underwent non-surgical treatment is shown in Table 1. None of the patients had distant metastasis at the start of treatment. There were statistically significant differences in patient’s age, T stage, N stage, and performance status between the groups. The patients who underwent non-surgical treatment were older, and had more advanced T and N stages, and had more severe performance status (Mann-Whitney U-test, 97
Survival for Resectable Oral Cancer
p < 0.05). On the other hand, there was no significant difference as to distribution of sex and primary tumour or clinical stage.
100 90 80 70 Survival (%)
The overall survival curve is shown in Figure 1. The overall survival probability rate of the surgicallytreated patients was 90% at 1 year, 76% at 2 years, and 61% at 5 years, while that of the non-surgically treated patients was 60%, 30%, and 15%, respectively. Among the non-surgically–treated patients, 5 died as a result of the tumour and 2 died of other disease (at 26 and 81 months) without clinical evidence of the tumour. The cause-specific survival curves are shown in Figure 2. The cause-specific survival probability of the surgically-treated patients was 90% at 1 year, 76% at 2 years, and 66% at 5 years (disease-free survival [DFS] was 64%). That of the non-surgically–treated patients was 60%, 30%,
60
Surgical treatment group
50 40 30 20
Non-surgical treatment group
10 0
20
40
60 80 100 Time (months)
140
160
Figure 1. Comparison of overall survival between the surgical treatment group (n = 53) and the non-surgical treatment group (n = 11). The survival rate of the surgical treatment group is significantly higher than that of the nonsurgical treatment group (log-rank test, p < 0.05).
Surgical treatment
No surgical treatment
Sex Female Male
23 (36%) 30 (47%)
3 (5%) 8 (12%)
Age (years) Median Range
64 39-83
75 49-87
p Value NS*
<0.05†
Primary site Tongue Lower gum Others Buccal mucosa Upper gum Floor of the mouth Oropharynx
20 15 18 8 4 5 1
1 6 4 1 0 1 2
T stage 2 3 4
13 17 23
0 1 10
N stage 0 1 2 3
14 14 25 0
1 1 8 1
Clinical stage III IV
17 36
1 10
Performance status 0 1 2 3
120
NS‡
<0.01†
<0.05†
NS*
<0.01† 36 13 2 2
3 4 2 2
Abbreviations: NS = no statistically significant difference. * Fisher’s exact probability test. † Mann-Whitney U-test ‡ Goodness test of fit for chi-square Table 1. Comparison of clinical data between the surgical treatment group and non-surgical treatment group.
98
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
Kurita, Kobayashi, Koike, et al
methods for advanced but resectable oral carcinoma compared with those who were treated by primary radical resection with appropriate adjuvant therapy.
100 90 80 Survival (%)
70
Surgical treatment group
60 50 40 30
Non-surgical treatment group
20 10 0
20
40
60 80 100 Time (months)
120
140
160
Figure 2. Comparison of cause-specific survival between the surgical treatment group (n = 53) and the non-surgical treatment group (n = 11). The survival rate of the surgical treatment group is significantly higher than that of the nonsurgical treatment group (log-rank test, p < 0.05).
and 30% (DFS, 18%), respectively. The median survival (Kaplan-Meier estimate) for the non-surgically treated patients was 12 months (cumulative proportion of survival at 8 months was 0.550). In both survival curves, the rate for the surgically-treated patients was significantly higher than that for the nonsurgically–treated patients (log-rank test, p < 0.05). Results from the survival analysis using the Cox proportional hazard model showed that the choice of treatment was a significant independent predictor for overall survival, while other factors had no influence on the survival (Table 2).
Discussion The purpose of this study was to estimate the probability of survival of patients treated by non-surgical Variables
Regression coefficient (± SE)
Relative risk
p Value
Treatment option Age (years) T stage N stage Performance status
-1.170 ± 0.509
0.310
0.02
0.012 ± 0.021 0.067 ± 0.290 0.197 ± 0.143 0.354 ± 0.254
1.012 1.069 1.218 1.425
0.58 0.82 0.17 0.16
Table 2. Multivariate analysis of the relationship between prognostic variables and overall survival using the Cox proportional hazard model.
Asian J Oral Maxillofac Surg Vol 15, No 2, 2003
The results of this study showed that the prognosis of the non-surgically–treated patients was poor. In the analysis of the cause-specific survival, the survival curve of the surgical therapy group showed a steady decrease during the first 33 months and became steady at 66%. There was a sharp decrease in the survival rate of the non-surgically–treated patients during the first 15 months, and the rate became steady at 30%. These data showed that for non-surgical treatments, the probability of survival from the disease was 30% and death would occur within 2 years. The rate was half that for patients who underwent radical surgery (67%). Recently, feasibility trials of chemoradiotherapy have received much attention. Some researchers used chemotherapy with concomitant radiation for advanced head and neck cancer and reported improved survival rates of 40% at 2 years,10 51% at 3 years,11 and 43% at 5 years.12 Some researchers used alternating chemotherapy and radiotherapy and reported better survival rates of 41% at 3 years5 and 67% at 5 years.13 In addition, several studies on the improvement of radiation therapy have been performed, including accelerated radiation treatment with or without concomitant boost.14,15 If the oncological effect were similar, these non-surgical treatments would replace primary surgery. It is recognised that there might be a selection bias in this study, in that the patients with older age, advanced cancer, or poor performance status selected the non-surgical treatments. No patient died of concurrent disease in the non-surgical treatment group. There were statistically significant differences in the distribution of patient’s age, T and N stage, and performance status between the groups. This result suggests that patients whose carcinomas were more advanced or who were older might have selected the non-surgical treatment. However, results from the survival analysis using the Cox proportional hazard model revealed that the option of treatment was a significant independent predictor for overall survival. 99
Survival for Resectable Oral Cancer
As a result of this retrospective study, it is possible to reconfirm the significant difference in the survival rate between surgical and non-surgical treatments in patients with advanced but resectable oral/oropharyneal cancer. Radical surgery may physically and mentally debilitate a patient, and patients may therefore be inclined to select non-surgical treatment. However, it is clear that non-surgical treatments are inferior to surgical treatments when it comes to survival. Currently, it is possible only to clearly inform patients about treatment modalities and their complications and prognoses, and allow them to make an informed decision when selecting treatment options.
References 1. Million RR, Cassisi NJ, editors. Management of head and neck cancer: a multidisciplinary approach. Philadelphia: Lippincott; 1994. 2. Franceschi D, Gupta R, Spiro RH, Shah JP. Improved survival in the treatment of squamous cell carcinoma of the oral tongue. Am J Surg 1993; s166:360-365. 3. Teichgraeber J, Bowman J, Geopfert H. New test series for the functional evaluation of oral cavity cancer. Head Neck Surg 1985;8:9-20. 4. Harrison JB, Zelefsky MJ, Armstrong JG, Capper E, Gaynor JJ, Sessions RB. Performance status after treatment for squamous cell cancer of the base of the tongue — comparison of primary radiation therapy versus primary surgery. Int J Radiat Oncol Biol Phys 1994;30;953-957. 5. Merlano M, Vitale V, Rosso R, Benasso M, Corvo R, Cavallari M, Sanguineti G, Bacigalupo A, Badellino F, Margarino G, Brema F, Pastorino G, Marziano G, Grimaldi A, Scasso F, Sperati G, Pallestrini E, Garaventa G, Accomando E, Cordone G, Comella, G, Daponte A, Rubagotti A, Bruzzi P, Santi L. Treatment of advanced squamous-cell carcinoma of the head and neck with alternating chemotherapy and radiotherapy. N Engl J Med 1992;327:1115-1121. 6. Adelstein DJ, Sharan VM, Damm C, Earle AS, Shah AC, Haria CD, Trey JE, Carter SG, Hines JD. Concurrent radiation therapy, 5-fluorouracil, and cisplatin for stage II, III, and IV, node-negative,
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Asian J Oral Maxillofac Surg Vol 15, No 2, 2003