Oral Oncology 50 (2014) 857–862
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Neck observation is appropriate in T1–2, cN0 oral squamous cell carcinoma without perineural invasion or lymphovascular invasion Chien-Fu Yeh a, Wing-Yin Li b, Muh-Hwa Yang c,d,e,f, Pen-Yuan Chu a, Yen-Ting Lu a, Yi-Fen Wang a, Peter Mu-Hsin Chang f, Shyh-Kuan Tai a,c,d,g,⇑ a
Departments of Otolaryngology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan Departments of Pathology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan Infection and Immunity Research Center, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan d Immunology Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan e Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan f Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan g Department of Otolaryngology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan b c
a r t i c l e
i n f o
Article history: Received 17 March 2014 Received in revised form 30 May 2014 Accepted 2 June 2014 Available online 4 July 2014 Keywords: Oral squamous cell carcinoma Perineural invasion Lymphovascular invasion Neck dissection Observation
s u m m a r y Objectives: Management of cN0 neck, elective neck dissection (END) or observation, remains controversial for T1–2 oral squamous cell carcinoma (OSCC). To allow for the safe observation of cN0 neck, it is mandatory to define predictors with high negative predictive value (NPV) for cervical lymph node (LN) status. Materials and Methods: Pathologic re-evaluation was performed in tumors of 253 consecutive patients with T1–2, cN0 OSCC. The predictive roles of pathologic parameters for cervical LN status in guiding neck management were investigated. Results: Cervical LN metastasis (LN+) occurred at a similar rate between observation and END groups (20.8% vs. 22.2%, p = 0.807), indicating poor discriminatory value for cervical LN status by clinical judgment. Compared with T classification, tumor thickness and differentiation, PNI/LVI (perineural invasion/lymphovascular invasion) demonstrated the highest NPV (85.5%). Hypothetically using PNI/LVI status to guide neck management, a dramatic reduction in overtreatment rate could be achieved (54.2% to 20.2%), with a minimal increase in undertreatment rate (6.3% to 9.9%). In patients without PNI or LVI (PNI/LVI ), the ultimate neck control rate (96.9% vs. 96.3%, p = 1.000) and 5-year disease-specific survival rate (91.1% vs. 92.8%, p = 0.863) were equivalent between observation and END. However, a significantly higher incidence of neck recurrence was found with observation (16.9% vs. 6.5%, p = 0.031), with 93.8% occurring within one year and 73.3% being successfully salvaged. Conclusion: Observation under close follow-up for the first year is appropriate in T1–2, cN0 OSCC without PNI or LVI, for the achievement of equivalent ultimate neck control and 5-year disease-specific survival rates compared with END. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction Surgery is the mainstay of treatment for T1–2 oral squamous cell carcinoma (OSCC). Cervical lymph node (LN) metastasis is a major poor prognostic factor, and occult metastasis can exist in 15–40% of patients presenting as clinical N0 (cN0) [1,2]. For the management of cN0 neck, elective neck dissection (END) has been ⇑ Corresponding author at: Department of Otolaryngology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan. Tel.: +886 2 2875 7337; fax: +886 2 2875 7338. E-mail address: [email protected] (S.-K. Tai). http://dx.doi.org/10.1016/j.oraloncology.2014.06.002 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
widely advocated to provide precise pathologic examination and better neck control [3–5]. However, END has not been shown to provide survival benefit in most studies [6–10]. Considering possible sequelae such as scarring and shoulder disability [11,12], END is an overtreatment for the majority of cN0 patients without occult metastasis. Sentinel LN biopsy (SLNB) has been reported as a promising alternative to END [13]. However, SLNB is technically demanding and still not considered a standard of care in routine practice [14,15]. Another treatment choice which has been shown to provide similar survival outcomes is observation [15,16]. Nevertheless, observation of cN0 neck with occult metastasis is obviously an undertreatment and carries the risk of advanced
858
C.-F. Yeh et al. / Oral Oncology 50 (2014) 857–862
disease progression. To date, no consensus regarding the optimal management has been made [17,18]. To safely observe cN0 neck, it is necessary to define parameters which effectively predict cervical LN status. The risk of cervical LN metastasis is commonly assessed by clinical judgment preoperatively, mainly based on T classification and thickness by physical examination. Both features can be further precisely evaluated by pathologic examination together [19] with additional parameters which has been known to correlate with the metastatic ability including differentiation [20,21], perineural invasion (PNI) [21–23] and lymphovascular invasion (LVI) [24,25]. PNI and LVI are established poor prognostic factors in human malignancies [26–28]. In head and neck cancers, PNI and LVI both correlate with advanced tumor stage and poor survival [22–25]. Our recent reports demonstrated that PNI and LVI both independently predict cervical LN metastasis in early T1–2 OSCC [29–31]. We therefore hypothesize that the absence of PNI or LVI may predict the lack of occult metastasis. In this study, we aimed to clarify the roles of PNI/LVI and other pathologic parameters in selecting T1–2, cN0 OSCC patients for neck observation. Materials and methods Patient population From June 2001 to August 2009, 272 consecutive newly diagnosed T1–2, cN0 OSCC patients underwent curative surgery at the Department of Otolaryngology, Taipei Veterans General Hospital. Patients with previous cancer history were excluded unless disease-free for >2 years. The cN0 status was determined by physical examination and imaging including computed tomography or magnetic resonance imaging. Nineteen patients who underwent neck observation were excluded as it was difficult to determine their initial cervical LN status because of: (1) arrangement of postoperative adjuvant therapy in 7; (2) development of local recurrence prior to neck recurrence in 1; and (3) short follow-up period 6 mm Pathologic T stage T1 T2 Differentiation Well Moderate/poor PNI/LVIa PNI/LVI PNI/LVI+ Cervical LN metastasisb LN LN+ Local recurrence No Yes Neck recurrence No Yes 5-year DSS (%) 5-year OS (%)
Obs no. (%)
END no. (%)
59 (76.6) 18 (23.4)
76 (43.2) 100 (56.8)
56 (72.7) 21 (27.3)
72 (40.9) 104 (59.1)
64 (83.1) 13 (16.9)
107 (60.8) 69 (39.2)
65 (84.4) 12 (15.6)
107 (60.8) 69 (39.2)
61 (79.2) 16 (20.8)
137 (77.8) 39 (22.2)
69 (89.6) 8 (10.4)
152 (86.4) 24 (13.6)
58 (75.3) 19 (24.7) 88.3 84.6
160 (90.9) 16 (9.1) 90.1 84.5
p
Contents lists available at ScienceDirect
Oral Oncology journal homepage: www.elsevier.com/locate/oraloncology
Neck observation is appropriate in T1–2, cN0 oral squamous cell carcinoma without perineural invasion or lymphovascular invasion Chien-Fu Yeh a, Wing-Yin Li b, Muh-Hwa Yang c,d,e,f, Pen-Yuan Chu a, Yen-Ting Lu a, Yi-Fen Wang a, Peter Mu-Hsin Chang f, Shyh-Kuan Tai a,c,d,g,⇑ a
Departments of Otolaryngology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan Departments of Pathology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan Infection and Immunity Research Center, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan d Immunology Center, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan e Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan f Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Taipei 11217, Taiwan g Department of Otolaryngology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan b c
a r t i c l e
i n f o
Article history: Received 17 March 2014 Received in revised form 30 May 2014 Accepted 2 June 2014 Available online 4 July 2014 Keywords: Oral squamous cell carcinoma Perineural invasion Lymphovascular invasion Neck dissection Observation
s u m m a r y Objectives: Management of cN0 neck, elective neck dissection (END) or observation, remains controversial for T1–2 oral squamous cell carcinoma (OSCC). To allow for the safe observation of cN0 neck, it is mandatory to define predictors with high negative predictive value (NPV) for cervical lymph node (LN) status. Materials and Methods: Pathologic re-evaluation was performed in tumors of 253 consecutive patients with T1–2, cN0 OSCC. The predictive roles of pathologic parameters for cervical LN status in guiding neck management were investigated. Results: Cervical LN metastasis (LN+) occurred at a similar rate between observation and END groups (20.8% vs. 22.2%, p = 0.807), indicating poor discriminatory value for cervical LN status by clinical judgment. Compared with T classification, tumor thickness and differentiation, PNI/LVI (perineural invasion/lymphovascular invasion) demonstrated the highest NPV (85.5%). Hypothetically using PNI/LVI status to guide neck management, a dramatic reduction in overtreatment rate could be achieved (54.2% to 20.2%), with a minimal increase in undertreatment rate (6.3% to 9.9%). In patients without PNI or LVI (PNI/LVI ), the ultimate neck control rate (96.9% vs. 96.3%, p = 1.000) and 5-year disease-specific survival rate (91.1% vs. 92.8%, p = 0.863) were equivalent between observation and END. However, a significantly higher incidence of neck recurrence was found with observation (16.9% vs. 6.5%, p = 0.031), with 93.8% occurring within one year and 73.3% being successfully salvaged. Conclusion: Observation under close follow-up for the first year is appropriate in T1–2, cN0 OSCC without PNI or LVI, for the achievement of equivalent ultimate neck control and 5-year disease-specific survival rates compared with END. Ó 2014 Elsevier Ltd. All rights reserved.
Introduction Surgery is the mainstay of treatment for T1–2 oral squamous cell carcinoma (OSCC). Cervical lymph node (LN) metastasis is a major poor prognostic factor, and occult metastasis can exist in 15–40% of patients presenting as clinical N0 (cN0) [1,2]. For the management of cN0 neck, elective neck dissection (END) has been ⇑ Corresponding author at: Department of Otolaryngology, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei 11221, Taiwan. Tel.: +886 2 2875 7337; fax: +886 2 2875 7338. E-mail address: [email protected] (S.-K. Tai). http://dx.doi.org/10.1016/j.oraloncology.2014.06.002 1368-8375/Ó 2014 Elsevier Ltd. All rights reserved.
widely advocated to provide precise pathologic examination and better neck control [3–5]. However, END has not been shown to provide survival benefit in most studies [6–10]. Considering possible sequelae such as scarring and shoulder disability [11,12], END is an overtreatment for the majority of cN0 patients without occult metastasis. Sentinel LN biopsy (SLNB) has been reported as a promising alternative to END [13]. However, SLNB is technically demanding and still not considered a standard of care in routine practice [14,15]. Another treatment choice which has been shown to provide similar survival outcomes is observation [15,16]. Nevertheless, observation of cN0 neck with occult metastasis is obviously an undertreatment and carries the risk of advanced
858
C.-F. Yeh et al. / Oral Oncology 50 (2014) 857–862
disease progression. To date, no consensus regarding the optimal management has been made [17,18]. To safely observe cN0 neck, it is necessary to define parameters which effectively predict cervical LN status. The risk of cervical LN metastasis is commonly assessed by clinical judgment preoperatively, mainly based on T classification and thickness by physical examination. Both features can be further precisely evaluated by pathologic examination together [19] with additional parameters which has been known to correlate with the metastatic ability including differentiation [20,21], perineural invasion (PNI) [21–23] and lymphovascular invasion (LVI) [24,25]. PNI and LVI are established poor prognostic factors in human malignancies [26–28]. In head and neck cancers, PNI and LVI both correlate with advanced tumor stage and poor survival [22–25]. Our recent reports demonstrated that PNI and LVI both independently predict cervical LN metastasis in early T1–2 OSCC [29–31]. We therefore hypothesize that the absence of PNI or LVI may predict the lack of occult metastasis. In this study, we aimed to clarify the roles of PNI/LVI and other pathologic parameters in selecting T1–2, cN0 OSCC patients for neck observation. Materials and methods Patient population From June 2001 to August 2009, 272 consecutive newly diagnosed T1–2, cN0 OSCC patients underwent curative surgery at the Department of Otolaryngology, Taipei Veterans General Hospital. Patients with previous cancer history were excluded unless disease-free for >2 years. The cN0 status was determined by physical examination and imaging including computed tomography or magnetic resonance imaging. Nineteen patients who underwent neck observation were excluded as it was difficult to determine their initial cervical LN status because of: (1) arrangement of postoperative adjuvant therapy in 7; (2) development of local recurrence prior to neck recurrence in 1; and (3) short follow-up period 6 mm Pathologic T stage T1 T2 Differentiation Well Moderate/poor PNI/LVIa PNI/LVI PNI/LVI+ Cervical LN metastasisb LN LN+ Local recurrence No Yes Neck recurrence No Yes 5-year DSS (%) 5-year OS (%)
Obs no. (%)
END no. (%)
59 (76.6) 18 (23.4)
76 (43.2) 100 (56.8)
56 (72.7) 21 (27.3)
72 (40.9) 104 (59.1)
64 (83.1) 13 (16.9)
107 (60.8) 69 (39.2)
65 (84.4) 12 (15.6)
107 (60.8) 69 (39.2)
61 (79.2) 16 (20.8)
137 (77.8) 39 (22.2)
69 (89.6) 8 (10.4)
152 (86.4) 24 (13.6)
58 (75.3) 19 (24.7) 88.3 84.6
160 (90.9) 16 (9.1) 90.1 84.5
p
