Ann Surg Oncol DOI 10.1245/s10434-014-3751-1
ORIGINAL ARTICLE – BONE AND SOFT TISSUE SARCOMAS
Prognostic Factors and Outcome of Spermatic Cord Sarcoma Stefano Radaelli, MD1, Anant Desai, MD, FRCS2, James Hodson, BSc3, Chiara Colombo, MD1, Keith Roberts, MD, PhD2, David Gourevitch, MD, FRCS2, and Alessandro Gronchi, MD1 Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Department of Surgery, Midland Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, Birmingham, UK; 3 Department of Statistics, Queen Elizabeth Hospital, Birmingham, UK 1
ABSTRACT Purpose. To evaluate management and outcome in a large series of patients with spermatic cord sarcomas (SCS), a rare malignancy. Methods. Eighty-two patients with localized SCS treated at two dedicated sarcoma units between 1992 and 2013 were included. Disease-specific survival (DSS) and crude cumulative incidence of local recurrence and distant metastases (DM) were estimated by Kaplan–Meier plots and log rank tests. Results. Median follow-up was 33 months (interquartile range 13–72 months). Sixty-one patients presented with primary disease. Liposarcoma was the most common histotype, but surprisingly, 37 % of tumors were of high grade. Seventeen patients (21 %) received radiotherapy and 12 patients (15 %) chemotherapy. Five-year DSS for the whole series was 92 % [95 % confidence interval (CI) 83–97]. Five-year rates of local recurrence and DM were 26 % (95 % CI 15–42) and 24 % (95 % CI 15–38), respectively. Tumor grade was found to be a significant predictor of both DSS and DM (both p \ 0.001). Quality of surgical margins was proved to affect the local outcome (p = 0.025), while the rates of distant metastases were found to differ significantly by histology (p = 0.010). Exclusively in the liposarcoma subgroup, quality of surgical margins was also directly associated with DSS (p = 0.043). Conclusions. Wide excision of the tumor is critical for cure, especially in the liposarcoma subgroup. The role of radiotherapy and chemotherapy is not established.
Ó Society of Surgical Oncology 2014 First Received: 27 February 2014 A. Gronchi, MD e-mail: [email protected]
Soft tissue sarcomas (STS) are rare tumors, with a world incidence of five new cases per 100,000 population per year.1 They mainly arise from the mesenchymal tissues of the limbs (50 %), the trunk and retroperitoneum (30– 40 %), and the head and neck (10 %).2 Sarcomas of the genitourinary tract account for less than 5 % of these tumors and less than 2 % of all urological malignancies. The spermatic cord is the most commonly involved urological site in male subjects (30 % of cases) but is frequently misdiagnosed.3 Spermatic cord sarcomas (SCS) typically present as a firm, painless, and irreducible unilateral groin or scrotal lumps. To the general surgeon or urologist, the most likely differential diagnosis is therefore an incarcerated inguinal hernia, inguinal lymphadenopathy, or testicular malignancy.4–7 Misdiagnosis frequently leads to incorrect surgery, where tumor excision can be incomplete with a subsequent risk of tumor recurrence. Surgery is the mainstay of treatment, while chemotherapy (CT) and/or radiotherapy (RT) are usually proposed in selected cases.8,9 Because of the small number of case series, prognostic factors and disease outcomes are not well established.6 The aim of the present study was to analyze a large series of patients with SCS treated at two major European tertiary centers with similar management protocols. PATIENTS AND METHODS Eighty-two consecutive patients with a histological diagnosis of localized SCS (primary or recurrent) treated at Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Italy, and Queen Elizabeth Hospital Birmingham, United Kingdom, between January 1992 and January 2013 were included. Patients presenting at our centers with more than one previous local recurrence (LR) and/or those with metastatic disease were excluded. Data reviewed included patient variables, pathological variables [tumor size, site (inguinal or intrascrotal),
S. Radaelli et al.
histological type (well-differentiated liposarcoma, dedifferentiated liposarcoma, or leiomyosarcoma), disease grade, and margin status], other treatment (neoadjuvant/ adjuvant RT or CT), and outcomes. Tumor size (in centimeters) was defined as the greatest dimension of the tumor in the surgical specimen or the dimension at the radiological imaging in case of preoperative treatment with a dimensional response. Histopathological diagnosis was reviewed at our institutions by expert pathologists and reclassified according to updated World Health Organization criteria.10 The FNCLCC (Fe´de´ration franc¸aise des centers de lutte contre le cancer) grading system was applied to all cases.11 Resections were classified as macroscopically complete (R0 and R1), absence of macroscopic tumor left behind, or incomplete (R2). All macroscopic complete resections were further classified according to the closest surgical margin, which was microscopically categorized as positive (tumor within 1 mm from the inked surface, R1) or negative (absence of tumor within 1 mm from the inked surface, R0). RT was provided in cases of presumed high risk of tumor recurrence due to local experience in the absence of consensus treatment protocols, given the limited clinical experience of treating patients with these tumors. When used, external beam RT was administered with doses ranging from 45 to 70 Gy (median, 60 Gy). CT was provided at the discretion of the multidisciplinary institutional sarcoma board/team or as part of a clinical trial. Anthracycline-based regimens were used, in most cases combined with ifosfamide. All patients received regular clinical and radiological review at least every 4 months for the first 2 years, every 6 months for the next 3 years, then yearly. This retrospective study was approved by the ethic committees of these institutions. The study end points were disease-specific survival (DSS) and incidence of LR or distant metastasis. In the analysis of DSS, deaths caused by conditions unrelated to sarcoma were censored. Disease-specific and disease-free outcomes were compared by using Kaplan–Meier plots and log rank tests. Reported survival rates are Kaplan–Meier estimates at fixed time points. All analysis were performed SPSS software, version 19 (IBM, Armonk, NY), with p \ 0.05 deemed to be indicative of statistical significance. A medical statistician performed all analyses. RESULTS The patient cohort, pathological variables, and treatments are summarized in Table 1. Only 12 patients (15 %) were initially operated on at a referring center. Forty-nine
TABLE 1 Patient and tumor characteristics Characteristic
Value
Patients
82
Age (year)
69 (60–77)
Tumor size, cm
5 (4–8)
Presentation Primary
61 (74 %)
Recurrent
21 (26 %)
Site Spermatic cord
71 (87 %)
Intrascrotal
11 (13 %)
Histotypes Well-differentiated liposarcoma Dedifferentiated liposarcoma
27 (33 %) 24 (29 %)
Leiomyosarcoma
17 (21 %)
Other (rhabdomyosarcoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma)
14 (17 %)
FNCLCC (grading) I
29 (35 %)
II
23 (28 %)
III Surgical procedure
30 (37 %)
Orchifunicolectomy
49 (60 %)
Mesh repair of inguinal canal
41 (50 %)
Bone resections
7 (9 %)
Vascular resections
3(4 %)
Visceral resections
3(4 %)
Lymphadenectomy
3(4 %)
Testicular prosthesis
3(4 %)
Flap/skin graft
1(1 %)
Margins R0
58 (71 %)
R1
24 (29 %)
Radiotherapy Yes
17 (21 %)
No
65 (79 %)
Chemotherapy Yes No
12 (15 %) 70 (85 %)
FNCLCC Fe´de´ration franc¸aise des centers de lutte contre le cancer
patients presented with primary disease after R0/R1 resection was performed in a local hospital, while 21 patients presented with recurrent tumor. Median follow-up was 36 months (interquartile range 13–72 months). All 82 patients received resection of spermatic cord and testicle, with 41 (50 %) requiring reconstruction with mesh. Locally advanced disease necessitated resection of a segment of bone in 7 patients (7 %), vascular resection with graft reconstruction in 3 (4 %), and visceral resection
Spermatic Cord Sarcoma
a
c Rate of Local Recurrence
1.0
Survival
0.8 0.6 0.4 0.2 0.0 0
25
50
75
100
1.0 0.8 0.6 0.4 0.2 0.0
125
0
25
Followup (Months)
1.0
Survival
0.8 0.6 0.4 0.2
p
ORIGINAL ARTICLE – BONE AND SOFT TISSUE SARCOMAS
Prognostic Factors and Outcome of Spermatic Cord Sarcoma Stefano Radaelli, MD1, Anant Desai, MD, FRCS2, James Hodson, BSc3, Chiara Colombo, MD1, Keith Roberts, MD, PhD2, David Gourevitch, MD, FRCS2, and Alessandro Gronchi, MD1 Sarcoma Service, Department of Surgery, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy; 2Department of Surgery, Midland Abdominal and Retroperitoneal Sarcoma Unit, Queen Elizabeth Hospital, Birmingham, UK; 3 Department of Statistics, Queen Elizabeth Hospital, Birmingham, UK 1
ABSTRACT Purpose. To evaluate management and outcome in a large series of patients with spermatic cord sarcomas (SCS), a rare malignancy. Methods. Eighty-two patients with localized SCS treated at two dedicated sarcoma units between 1992 and 2013 were included. Disease-specific survival (DSS) and crude cumulative incidence of local recurrence and distant metastases (DM) were estimated by Kaplan–Meier plots and log rank tests. Results. Median follow-up was 33 months (interquartile range 13–72 months). Sixty-one patients presented with primary disease. Liposarcoma was the most common histotype, but surprisingly, 37 % of tumors were of high grade. Seventeen patients (21 %) received radiotherapy and 12 patients (15 %) chemotherapy. Five-year DSS for the whole series was 92 % [95 % confidence interval (CI) 83–97]. Five-year rates of local recurrence and DM were 26 % (95 % CI 15–42) and 24 % (95 % CI 15–38), respectively. Tumor grade was found to be a significant predictor of both DSS and DM (both p \ 0.001). Quality of surgical margins was proved to affect the local outcome (p = 0.025), while the rates of distant metastases were found to differ significantly by histology (p = 0.010). Exclusively in the liposarcoma subgroup, quality of surgical margins was also directly associated with DSS (p = 0.043). Conclusions. Wide excision of the tumor is critical for cure, especially in the liposarcoma subgroup. The role of radiotherapy and chemotherapy is not established.
Ó Society of Surgical Oncology 2014 First Received: 27 February 2014 A. Gronchi, MD e-mail: [email protected]
Soft tissue sarcomas (STS) are rare tumors, with a world incidence of five new cases per 100,000 population per year.1 They mainly arise from the mesenchymal tissues of the limbs (50 %), the trunk and retroperitoneum (30– 40 %), and the head and neck (10 %).2 Sarcomas of the genitourinary tract account for less than 5 % of these tumors and less than 2 % of all urological malignancies. The spermatic cord is the most commonly involved urological site in male subjects (30 % of cases) but is frequently misdiagnosed.3 Spermatic cord sarcomas (SCS) typically present as a firm, painless, and irreducible unilateral groin or scrotal lumps. To the general surgeon or urologist, the most likely differential diagnosis is therefore an incarcerated inguinal hernia, inguinal lymphadenopathy, or testicular malignancy.4–7 Misdiagnosis frequently leads to incorrect surgery, where tumor excision can be incomplete with a subsequent risk of tumor recurrence. Surgery is the mainstay of treatment, while chemotherapy (CT) and/or radiotherapy (RT) are usually proposed in selected cases.8,9 Because of the small number of case series, prognostic factors and disease outcomes are not well established.6 The aim of the present study was to analyze a large series of patients with SCS treated at two major European tertiary centers with similar management protocols. PATIENTS AND METHODS Eighty-two consecutive patients with a histological diagnosis of localized SCS (primary or recurrent) treated at Fondazione IRCCS Istituto Nazionale dei Tumori Milan, Italy, and Queen Elizabeth Hospital Birmingham, United Kingdom, between January 1992 and January 2013 were included. Patients presenting at our centers with more than one previous local recurrence (LR) and/or those with metastatic disease were excluded. Data reviewed included patient variables, pathological variables [tumor size, site (inguinal or intrascrotal),
S. Radaelli et al.
histological type (well-differentiated liposarcoma, dedifferentiated liposarcoma, or leiomyosarcoma), disease grade, and margin status], other treatment (neoadjuvant/ adjuvant RT or CT), and outcomes. Tumor size (in centimeters) was defined as the greatest dimension of the tumor in the surgical specimen or the dimension at the radiological imaging in case of preoperative treatment with a dimensional response. Histopathological diagnosis was reviewed at our institutions by expert pathologists and reclassified according to updated World Health Organization criteria.10 The FNCLCC (Fe´de´ration franc¸aise des centers de lutte contre le cancer) grading system was applied to all cases.11 Resections were classified as macroscopically complete (R0 and R1), absence of macroscopic tumor left behind, or incomplete (R2). All macroscopic complete resections were further classified according to the closest surgical margin, which was microscopically categorized as positive (tumor within 1 mm from the inked surface, R1) or negative (absence of tumor within 1 mm from the inked surface, R0). RT was provided in cases of presumed high risk of tumor recurrence due to local experience in the absence of consensus treatment protocols, given the limited clinical experience of treating patients with these tumors. When used, external beam RT was administered with doses ranging from 45 to 70 Gy (median, 60 Gy). CT was provided at the discretion of the multidisciplinary institutional sarcoma board/team or as part of a clinical trial. Anthracycline-based regimens were used, in most cases combined with ifosfamide. All patients received regular clinical and radiological review at least every 4 months for the first 2 years, every 6 months for the next 3 years, then yearly. This retrospective study was approved by the ethic committees of these institutions. The study end points were disease-specific survival (DSS) and incidence of LR or distant metastasis. In the analysis of DSS, deaths caused by conditions unrelated to sarcoma were censored. Disease-specific and disease-free outcomes were compared by using Kaplan–Meier plots and log rank tests. Reported survival rates are Kaplan–Meier estimates at fixed time points. All analysis were performed SPSS software, version 19 (IBM, Armonk, NY), with p \ 0.05 deemed to be indicative of statistical significance. A medical statistician performed all analyses. RESULTS The patient cohort, pathological variables, and treatments are summarized in Table 1. Only 12 patients (15 %) were initially operated on at a referring center. Forty-nine
TABLE 1 Patient and tumor characteristics Characteristic
Value
Patients
82
Age (year)
69 (60–77)
Tumor size, cm
5 (4–8)
Presentation Primary
61 (74 %)
Recurrent
21 (26 %)
Site Spermatic cord
71 (87 %)
Intrascrotal
11 (13 %)
Histotypes Well-differentiated liposarcoma Dedifferentiated liposarcoma
27 (33 %) 24 (29 %)
Leiomyosarcoma
17 (21 %)
Other (rhabdomyosarcoma, solitary fibrous tumor, synovial sarcoma, undifferentiated pleomorphic sarcoma, myxofibrosarcoma)
14 (17 %)
FNCLCC (grading) I
29 (35 %)
II
23 (28 %)
III Surgical procedure
30 (37 %)
Orchifunicolectomy
49 (60 %)
Mesh repair of inguinal canal
41 (50 %)
Bone resections
7 (9 %)
Vascular resections
3(4 %)
Visceral resections
3(4 %)
Lymphadenectomy
3(4 %)
Testicular prosthesis
3(4 %)
Flap/skin graft
1(1 %)
Margins R0
58 (71 %)
R1
24 (29 %)
Radiotherapy Yes
17 (21 %)
No
65 (79 %)
Chemotherapy Yes No
12 (15 %) 70 (85 %)
FNCLCC Fe´de´ration franc¸aise des centers de lutte contre le cancer
patients presented with primary disease after R0/R1 resection was performed in a local hospital, while 21 patients presented with recurrent tumor. Median follow-up was 36 months (interquartile range 13–72 months). All 82 patients received resection of spermatic cord and testicle, with 41 (50 %) requiring reconstruction with mesh. Locally advanced disease necessitated resection of a segment of bone in 7 patients (7 %), vascular resection with graft reconstruction in 3 (4 %), and visceral resection
Spermatic Cord Sarcoma
a
c Rate of Local Recurrence
1.0
Survival
0.8 0.6 0.4 0.2 0.0 0
25
50
75
100
1.0 0.8 0.6 0.4 0.2 0.0
125
0
25
Followup (Months)
1.0
Survival
0.8 0.6 0.4 0.2
p
