Histologic subtype and margin of resection predict pattern of recurrence and survival for retroperitoneal liposarcoma

OBJECTIVE: The aim of this study was to determine the pattern of recurrence and prognostic significance of histologic subtype in a large series of patients with primary retroperitoneal liposarcoma. SUMMARY BACKGROUND DATA: Classification of liposarcoma into subtypes, based on morphologic features and cytogenetic aberrations, is now widely accepted. Previous studies have shown that high histologic grade and incomplete gross resection are the most important prognostic factors for survival in patients with retroperitoneal sarcoma and suggest that patients with liposarcoma have a 3-fold higher risk of local recurrence compared with other histologies. METHODS: A prospective database was used to identify 177 patients with primary retroperitoneal liposarcoma treated between July 1982 and June 2002. Histology at primary presentation was reviewed by a sarcoma pathologist and subtyped into 4 distinct groups according to strict criteria. The influence of clinicopathological factors on local recurrence, distant recurrence, and disease-specific survival was analyzed. RESULTS: Of 177 patients with primary retroperitoneal liposarcoma operated on for curative intent, 99 (56%) presented with well-differentiated, 65 (37%) with dedifferentiated, 9 (5%) with myxoid, and 4 (2%) with round cell morphology. The tumor burden was determined by the sum of the maximum tumor diameters. The median tumor burden was 26 cm (5-139). Median follow-up time for 92 (52%) surviving patients was 37 (mean, 0.5-192) months. Multivariate analysis showed that dedifferentiated liposarcoma subtype was associated with a 6-fold increased risk of death compared with well-differentiated histology (P < 0.0001). In addition to histologic subtype, incomplete resection (P < 0.0001), contiguous organ resection (excluding nephrectomy; P = 0.05), and age (P = 0.03) were important independent prognostic factors for survival in retroperitoneal liposarcoma. Retroperitoneal dedifferentiated liposarcoma was associated with an 83% local recurrence rate and 30% distant recurrence rate at 3 years. CONCLUSIONS: The histologic subtype and margin of resection are prognostic for survival in primary retroperitoneal liposarcoma. Dedifferentiated histologic subtype and the need for contiguous organ resection (excluding nephrectomy) was associated with an increase risk of local and distant recurrence. Nephrectomy may be needed to achieve complete resection, but has no measurable influence on disease specific survival.     

Adult genitourinary sarcoma: the 25-year Memorial Sloan-Kettering experience

PURPOSE: Urological sarcomas are rare. We describe a continued single institutional experience during 25 years. MATERIALS AND METHODS: The records from July 1977 to July 2003 were reviewed of all patients at our institution with sarcoma arising in the urinary tract or male genital system who were 16 years or older at diagnosis. RESULTS: The primary tumor site in 131 patients was the bladder in 20, the kidney in 26, paratesticular in 57, the prostate in 21 and other in 7. Median followup was 4.0 years. The most common histological subtypes were leiomyosarcoma in 29% of cases and liposarcoma in 26%. Median tumor size was 7 cm and 78% of lesions were high grade. Of the patients 28 (21%) presented with metastatic disease and their median survival was 1.4 years compared to 10.7 years in patients without metastatic disease (p < 0.0001). Disease specific survival was 56% and 42% at 5 and 10 years, respectively and median survival was 7.6 years. On univariate analysis unfavorable prognostic variables for disease specific survival were metastasis at presentation, high tumor grade, a lack of leiomyosarcoma and liposarcoma histological subtypes, prostate sarcoma and large tumor size, incomplete surgical resection and positive surgical margin. Patient sex, age and surgical margin status were not significant predictors. On multivariate analysis 2 variables remained significant predictors of disease specific survival, including tumor size (HR 1.1, 95% CI 1.02 to 1.17) and absent metastasis at diagnosis (HR 4.9, 95% CI 1.4 to 17.2). CONCLUSIONS: Predictors of disease specific survival include local disease at presentation, complete tumor resection and tumor grade, size, location and histological subtype. With adequate surgical treatment most patients who presented with primary disease and underwent complete surgical resection achieved prolonged disease specific survival.     

The impact of chemotherapy on the survival of patients with high-grade primary extremity liposarcoma

OBJECTIVE: To determine if chemotherapy offers a survival benefit to patients with large, high-grade, primary extremity liposarcoma. SUMMARY BACKGROUND DATA: The impact of chemotherapy on the survival of patients with primary extremity soft tissue sarcoma is controversial and its effect on individual histologic subtypes is not defined. PATIENT AND METHODS: Two prospectively collected sarcoma databases were used to identify all patients with >5 cm, high-grade, primary extremity liposarcoma that underwent surgical treatment of cure from 1975 to 2003 (n = 245). Clinical, pathologic and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS) and local recurrence-free survival (LRFS). RESULTS: Sixty-three (26%) patients were treated with ifosfamide based chemotherapy (IF), 83 (34%) with doxorubicin based chemotherapy (DOX) and 99 (40%) received no chemotherapy (NoC). To assess the impact of DOX, a contemporary cohort analysis of patients treated from 1975 to 1990 was performed. The 5 year DSS of the DOX treated patients was 64% (53%-74%) compared with 56% (51%-79%) for the NoC patients (log-rank P value = 0.28). To assess the impact of IF, a contemporary cohort analysis of patients treated from 1990 to 2003 was performed. The 5 year DSS of the IF treated patients was 92% (84%-100%) compared with 65% (51%-79%) for the NoC patients (log-rank P value = 0.0003). Independent prognostic factors for improved DSS were smaller size (HR = 0.7, P = 0.01), myxoid/round cell histologic subtype (HR = 0.3, P = 0.03) and treatment with IF (HR = 0.3, P = 0.01). The five-year DRFS of the IF treated patients was 81% (70%-92%) compared with 63% (50%-76%) for the NoC patients (log-rank P value = 0.02). The 5 year LRFS of the IF treated patients was 86% (76%-96%) compared with 87% (77%-97%) for the NoC patients (log-rank P value = 0.99). CONCLUSIONS: In patients with large, high-grade, primary extremity liposarcoma; DOX is not associated with improved DSS and IF is associated with an improved DSS. Treatment with IF should be considered in patients with high-risk primary extremity liposarcoma.     

Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers

Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P<0.001), and both also correlated with histologic type (P<0.001 and P=0.01, respectively), p16 status (P=0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P<0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.     

Chemotherapy is associated with improved survival in adult patients with primary extremity synovial sarcoma

PURPOSE: To determine if ifosfamide-based chemotherapy (IF) offers a survival benefit to adult patients with primary extremity synovial sarcoma. PATIENTS AND METHODS: Prospectively collected patient data from 2 institutions was used to identify all adult patients (>or=16 years) with >or=5 cm, deep, primary, extremity, synovial sarcoma that underwent surgical treatment of cure from 1990 to 2002. A total of 101 patients were identified and the median follow-up for survivors was 58 months. Clinical, pathologic, and treatment variables were analyzed for disease-specific survival (DSS), distant recurrence-free survival (DRFS), and local recurrence-free survival (LRFS). RESULTS: Sixty-eight (67%) patients were treated with IF and 33 (33%) patients received no chemotherapy (NoC) for the primary tumor. The characteristics of the IF-treated patients [median tumor size = 7.2 cm; monophasic n = 46 (68%)] were similar to NoC patients [median tumor size = 7 cm; monophasic n = 23 (70%)]. The 4-year DSS of the IF-treated patients was 88% compared with 67% for the NoC patients (P = 0.01). Smaller size (HR = 0.3 per 5-cm decrease, P < 0.0001) and treatment with IF (HR = 0.3 compared with NoC, P = 0.007) were independently associated with an improved DSS. Treatment with IF was independently associated with an improved DRFS (HR = 0.4, P = 0.03) but not associated with an improved LRFS (P = 0.39). CONCLUSION: Ifosfamide-based chemotherapy was associated with an improved DSS in adult patients with high-risk, primary, extremity, synovial sarcoma and should be considered in the treatment of such patients.     

Outcome of the treatment of invasive non-transitional cell carcinoma

BACKGROUND: We evaluated the treatment outcomes of non-transitional cell carcinoma (non-TCC) cases after radical cystectomy. METHODS: Radical cystectomy was performed in 259 invasive bladder cancer patients in our department and of these, 59 (22.7%) were non-TCC. Primary squamous cell carcinomas (SCC), adenocarcinomas and undifferentiated cancers (UC) were grouped as non-TCC of the bladder. Of the 59 non-TCC; 32 SCC, 20 UC, five adenocarcinoma and two sarcomatoid tumor cases were demonstrated. RESULTS: The 5-year disease-specific survival rate of TCC and non-TCC cases were 48.9 and 28.2%, respectively (P = 0.0016). The 5-year disease-specific survival rates of SCC and UC were 25.1 and 23.4%, respectively. The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 6 months, respectively (P = 0.4579). The disease-specific survival rates of TCC and non-TCC cases at stage pT2NoMo were 79.1 and 27.2%, respectively (P = 0.0000). The median survival time of SCC, UC and adenocarcinoma cases were 19, 12 and 13.3 months, respectively, for the same stage. The survival time of TCC, SCC and UC cases at stage pT3NoMo were 23, 26 and 45 months, respectively (P = 0.2307). The median survival time at stages pT2-3N1Mo for the same groups were 18, 16 and 11 months, respectively (P = 0.0939). CONCLUSION: The study presented here demonstrates that both TCC and non-TCC cases have poor survival rates in locally advanced disease and that at the pT2NoMo stage the prognosis of non-TCC cases is poor when compared with TCC cases.     

Surgical treatment and outcomes of patients with primary inferior vena cava leiomyosarcoma

BACKGROUND: The inferior vena cava (IVC) is a rare site for primary soft tissue sarcoma. There are limited data in the literature regarding surgical management of the IVC and longterm survival of these patients. STUDY DESIGN: From 1982 to 2002, a total of 25 patients with primary IVC leiomyosarcoma was treated as inpatients and followed in a prospective database at Memorial Sloan-Kettering. Presenting symptoms, tumor characteristics, operative management, postoperative morbidity, and disease-specific survival were assessed for each patient. RESULTS: The 25 patients with primary IVC leiomyosarcoma accounted for 0.5% of all adult patients with soft tissue sarcoma treated during this time. The median patient age was 56 years (range 41 to 79 years). The three most common presenting symptoms were abdominal pain (52%), distention (20%), and deep venous thrombosis (12%). Of the patients, 21 (84%) underwent complete resection of the tumor. The IVC was managed in one of three ways: ligation (n = 11), primary/patch repair (n = 8), and expanded polytetrafluoroethylene tube grafting (n = 2). Among patients undergoing IVC ligation and primary/patch repair (n = 19), 11% had severe postoperative edema and none had worsening renal function. Local recurrence occurred in 33% of patients and distant recurrence occurred in 48% of patients. Patients undergoing complete resection had 3-year and 5-year disease-specific survival rates of 76% and 33%, respectively. There were no 3-year survivors among patients with incomplete resections. CONCLUSIONS: Complete resection of primary IVC leiomyosarcomas is feasible and associated with improved survival. The IVC can be managed by primary repair or ligation with a low risk of severe postoperative edema.     

The prevalence and clinicopathologic correlate of p16INK4a, retinoblastoma and p53 immunoreactivity in locally advanced urinary bladder cancer

The purpose of the study was to investigate the prognostic value and clinicopathological correlate of tumor p53, p16 and Rb protein expression in patients with locally advanced urinary bladder cancer. Sixty-five patients (44 men and 21 women; 40 to 84 yrs old) with locally advanced urinary bladder cancer (21 pT2, 27pT3, 17pT4) undergoing radical cystectomy and bilateral pelvic lymph node dissection were followed up for 2 to 116 months (mean +/- SD: 30.02 +/- 6.46 months). Immunohistochemical staining for p53, Rb and p16 proteins were performed on surgically obtained, formalin fixed and paraffin embedded tissue sections. Thirty of the tumors (46.2%) were p53+, 52 of the tumors (80%) were p16- and 41 (63%) were Rb-. Only 5 of the tumors (7.7%) had normal expression of all three proteins. The tumor expression status of p53 could not be correlated with p16 (P = 1.000) or Rb (P = 1.000). Only a marginal inverse relationship was found between the expression of p16 and Rb (P = 0.056). Higher grade tumors had significantly lower percentage of p16 abnormality (P = 0.05), while higher grade (not higher stage) tumors had higher percentage of Rb abnormality (P = 0.0245). Univariate analysis showed that tumor expression of Rb or p16, alone or combined, had no predictive value on progression-free and disease-specific survival. It did, however, show a significant correlation between progression-free survival and tumor p53 and LN status (P = 0.032 and P = 0.0304) and a significant correlation between tumor stage disease-specific survival (P = 0.042). Multivariate analysis showed tumor stage and nodal status to be two significant independent indicators for progression-free survival (P = 0.0038 and P = 0.0049) and disease-specific survival (P = 0.0066 and P = 0.0484). It was also noteworthy that, after receiving postoperative adjuvant systemic M-VEC chemotherapy, patients with node-positive p53-normal tumors had significantly better progression-free and disease-specific survivals than those with node-positive p53-abnormal tumors (P = 0.036 and P = 0.0479, respectively). This study has found tumor expression of p53, p16 and Rb proteins in locally advanced bladder cancer to be frequently abnormal. Although multivariate analysis showed tumor stage and nodal status to be the only two statistically significant parameters, p53 may also serve as an additional prognostic predictor of the outcome of postoperative adjuvant systemic chemotherapy in patients with regional lymph node tumor involvement. Such patients with p53-normal tumors experienced significantly better progression-free and disease-specific survivals than those with p53-abnormal tumors.     

Results of a single-center experience with resection and ablation for sarcoma metastatic to the liver

HYPOTHESIS: A subset of patients with sarcoma liver metastasis may benefit from hepatic resection and/or ablation. DESIGN: Retrospective review of prospectively collected cancer center database records. PATIENTS AND METHODS: Sixty-six patients who underwent hepatic resection and/or open radiofrequency ablation of metastatic sarcoma between July 1, 1996, and April 30, 2005, were identified from the database. Clinicopathologic, operative, recurrence, and long-term survival data were analyzed. RESULTS: The primary sarcoma site was the abdomen or retroperitoneum (n = 22), stomach (n = 18), small or large bowel (n = 17), pelvis (n = 4), uterus (n = 3), or other (n = 2). Tumor pathologic types included gastrointestinal stromal tumor (n = 36), leiomyosarcoma (n = 18), and sarcoma not otherwise classified (n = 12). Thirty-five patients underwent resection, 18 underwent resection plus radiofrequency ablation, and 13 underwent radiofrequency ablation only. With a median follow-up of 35.8 months, 44 patients (66.7%) had recurrence (intrahepatic only, n = 16; extrahepatic only, n = 11; both, n = 17). Treatment with radiofrequency ablation (either alone or combined with resection) (P = .002) and lack of adjuvant chemotherapy (P = .01) predicted shorter disease-free survival. The 1-, 3-, and 5-year overall survival rates were 91.2%, 65.4%, and 27.1%, respectively. Patients with gastrointestinal stromal tumor who were treated with adjuvant imatinib mesylate had the longest median survival (not reached) (P = .003). CONCLUSIONS: Long-term survival can be achieved following surgical treatment of sarcoma liver metastasis, especially in patients with gastrointestinal stromal tumor. Patients with sarcoma liver metastasis should be evaluated by a multidisciplinary team, as recurrence is common and adjuvant therapy may prolong survival.     

Subtype specific prognostic nomogram for patients with primary liposarcoma of the retroperitoneum, extremity, or trunk

OBJECTIVE: To determine the prognostic significance of histologic subtype in a large series of patients with primary liposarcoma (LS) and to construct a LS-specific postoperative nomogram for disease-specific survival (DSS). SUMMARY BACKGROUND DATA: Nomograms, used to define and predict outcome following operative intervention, may contain variables not conventionally used in standard staging systems. A 12-year DSS postoperative nomogram for all sarcomas has already been established. METHODS: From a single-institution prospective sarcoma database, patients with primary extremity, truncal, or retroperitoneal LS treated between 1982 and 2005 were identified. Histology was reviewed by a sarcoma pathologist and divided into 5 subtypes. A nomogram predictive of 5- and 12-year DSS was developed. RESULTS: Of 801 patients with primary LS resected with curative intent, 369 (46%) presented with well-differentiated, 143 (18%) dedifferentiated, 144 (18%) myxoid, 81 (10%) round cell, and 64 (8%) pleomorphic histology. The median tumor burden was 15 cm (range, 1-139 cm). At last follow-up, 560 patients were alive with a median follow-up time of 45 months (range, 1-264 months) and 51 months for surviving patients. The 5- and 12-year DSS rates were 83% (95% confidence interval [CI], 80%-86%) and 72% (95% CI, 67%-77%), respectively. The nomogram was drawn on the basis of a Cox regression model. The independent predictors of DSS were age, presentation status, histologic variant, primary site, tumor burden, and gross margin status. The nomogram was internally validated using bootstrapping and shown to have excellent calibration. The concordance index was 0.827 compared with 0.776 for the general sarcoma postoperative nomogram for 12-year DSS. CONCLUSION: The LS-specific nomogram based on histologic subtype provides more accurate survival predictions for patients with primary LS than the previously established generic sarcoma nomogram. DSS nomograms aid in more accurate counseling of patients, identification of patients appropriate for adjuvant therapy, and stratification of patients for clinical trials and molecular analysis.     

Adult genitourinary sarcoma: A population-based analysis of clinical characteristics and survival

Background: Sarcomas of the genitourinary (GU) tract are exceedingly rare, accounting for just 1% to 2% of malignancies treated by urologic surgeons. We perform a thorough investigation of incidence and mortality in the United States using the Surveillance, Epidemiology, and End Results (SEER) database. Patients and Methods: The SEER 18 database was used to identify patients diagnosed with genitourinary sarcoma over the age of 16. Data on demographics and tumor characteristics were collected. Survival analysis was performed on the most common primary tumor sites. Results: The search identified 3,007 patients with GU sarcomas from 1973 to 2015. In order of descending incidence, tumors presented in the bladder, kidney, paratestis, and scrotum. Amongst sarcomas arising in the bladder, leiomyosarcomas exhibited the longest median survival time (overall survival (OS) 62 months), while carcinosarcomas had the shortest (OS 9 months). Metastatic disease decreased leiomyosarcoma OS to 3 months. When comparing renal tumors, liposarcomas had the longest median survival time (OS 45 months) and carcinosarcomas had the shortest (OS 6 months). Older age (P < 0.001 and P = 0.015) and T4 disease (P = 0.005 and P < 0.001) predicted for worse survival amongst bladder and renal sarcomas, respectively. High tumor grade (P < 0.001) and node positive disease (P = 0.024) also affected survival amongst renal tumors. Conclusions: Tumors most commonly present in the bladder, kidney, paratestis, and scrotum, with kidney sarcomas having markedly dismal survival outcomes. Survival of identical histologic types varied by primary tumor location, suggesting that treatment strategies should be refined by type of sarcoma and primary tumor location within the GU tract.     

Characteristics and prognosis of resected T3 non-small cell lung cancer

AIM: The aim this study is to determine the characteristics, survival, and factors affecting the survival of resected T3 non-small cell lung cancer. METHODS: The records of 97 cases were retrospectively reviewed with T3 non-small cell lung cancer patients that were operated between 1996-2001. Complete resection was achieved in 71 (73.2%) patient. The distribution of N status was 47.4%, 28.9%, and 23.7% for N0, N1 and N2 respectively. The evaluated prognostic factors in univariate and multivariate analyses were, histologic type, type of resection, N status, subgroups of pT3, resection margins and effect of adjuvant therapy. RESULTS: Overall 5-year survival rate was 24.3%. Median survival and 5-year survival of the patients whose tumors resected completely was 33 months and 31.5%, whereas 18 months and 7.3% for the patients resected incompletely (P=0.03). Median survival being not significantly different among the three subgroups: 25, 23, and 32 months (P=0.7) in the bronchial pT3, mediastinal pT3, and peripheral pT3 subgroups, respectively. Histology (P=0.57), type of surgical resection (lobectomy versus pneumonectomy) (P=0.25), and use of adjuvant therapy (P=0.054) did not influence the survival significantly. However N status influenced the survival significantly (P=0.01). According to the multivariate analyses, two factors were selected as prognostic indicators: N2 status (P=0.03) and incomplete resection (P=0.03). CONCLUSION: Three pT3 subgroups did not show survival differences. Complete resection and N2 status are the two most influencing factors in survival of the patients. Adjuvant therapy effected the survival and the quality of life reversely.     

Clinical features of leiomyosarcoma of the urinary bladder: Analysis of 183 cases

IntroductionExperience with management of urinary bladder leiomyosarcoma (LMS) is rare. Therefore, to better elucidate the disease characteristics of urinary bladder LMS, we utilized a large population-based cancer registry to examine the epidemiology, natural history, pathological characteristics, prognostic factors, and treatment outcomes.Material and methodsThe Surveillance, Epidemiology, and End Results database (1973–2010) was used to identify cases by tumor site and histology codes. The association between clinical and demographic characteristics and long-term survival was examined.ResultsA total of 183 histologically confirmed cases were identified between 1973 and 2010. The annual age-adjusted incidence rate was 0.23 cases per 1,000,000 and did not significantly change over time. Median age of the patients was 65 years (interquartile range: 47–78 y). Of the patients with a known pathologic tumor stage (n = 164), 50% had a regional or distant disease. Overall, 63.2% of patients with known histologic grade (n = 106), had poorly differentiated or undifferentiated histology. Most patients (92.9%) received cancer-directed surgery (CDS), with 34.4% having radical or partial cystectomy. Only 7.7% of patients received radiation therapy in combination with surgery. The median disease-specific survival was 46 months. Five- and 10-year cancer-specific survival rates were 47%, and 35%, respectively. On multivariate analysis, a worse outcome was associated with an undifferentiated tumor grade, distant disease, and failure to undergo CDS.ConclusionThis series represents the largest cohort of LMS of the urinary bladder studied to date. LMS commonly presented as high grade and advanced stage with a poor prognosis. Reduced disease-specific survival was associated with increasing age, undifferentiated tumor grade, distant disease, and failure to undergo CDS.     

Analysis of the prognostic significance of microscopic margins in 2,084 localized primary adult soft tissue sarcomas

OBJECTIVE: To define the significance of positive microscopic resection margins in a large cohort treated for soft tissue sarcoma. METHODS: The authors analyzed 2,084 patients with localized primary soft tissue sarcoma (all anatomic sites) treated from 1982 to 2000. Clinicopathologic variables studied included tumor site, size, depth, histologic type, grade, and resection margin status. Treatment other than resection was not analyzed. Study endpoints included local and distant recurrence-free and disease-specific survival rates, estimated by the Kaplan-Meier method. Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 50 months. After primary resection, 1,624 (78%) patients had negative and 460 (22%) had positive resection margins. Having positive margins nearly doubled the risk of local recurrence and increased the risk of distant recurrence and disease-related death. Seventy-two percent of patients with positive margins had no recurrence. Resection margin did not predict local control for retroperitoneal sarcomas or fibrosarcomas. Resection margin remained significantly associated with distant recurrence-free survival and disease-specific survival across all subsets after adjusting for other prognostic variables. The overall 5-year disease-specific survival rates for negative and positive margins were 83% and 75%. CONCLUSIONS: Positive microscopic resection margins significantly decrease the local recurrence-free survival rate for other-than-primary fibrosarcoma and retroperitoneal sarcomas, and independently predict distant recurrence-free survival rates and disease-specific survival rates for all patient subsets. Adjuvant therapy should be considered in the management of soft tissue sarcoma to increase local control. Because 72% of positive margins did not equate with inevitable local recurrence, considerable clinical judgment is required in considering additional treatment. Microscopic resection margins should be considered for inclusion in staging systems and treatment algorithms that address local recurrence.     

ADULT PROSTATE SARCOMA: THE M. D. ANDERSON CANCER CENTER EXPERIENCE

PURPOSE: Sarcoma of prostate origin is rare. Historically, long-term survival rates for adult patients with prostate sarcoma are poor. We analyzed the experience of 1 institution with prostate sarcoma during the last 3 decades. MATERIALS AND METHODS: The records of 21 patients with prostate sarcoma were reviewed to identify symptoms at presentation, diagnostic procedures, presence and development of metastases, staging evaluation, histological subtype, grade and size of the primary tumor, and treatment sequence, including surgery, and preoperative and postoperative therapies. Several clinicopathological variables were assessed for prognostic importance. RESULTS: Most patients presented with urinary obstruction. The diagnosis of prostate sarcoma was usually established with ultrasound guided biopsy or transurethral resection. Histological subtypes were leiomyosarcoma in 12, rhabdomyosarcoma in 4, malignant fibrous histiocytoma in 1 and unclassified sarcoma in 4 patients. At last followup, 8 patients had no evidence of disease after a median of 81.5 months (range 10 to 197). The remaining 13 patients died of sarcoma (median survival 18 months, range 3 to 94). The 1, 3 and 5-year actuarial survival rates for all 21 patients were 81%, 43% and 38%, respectively. Factors predictive of long-term survival were negative surgical margins (p = 0.0005) and absence of metastatic disease at presentation (p = 0.0004). Tumor size and grade, and the histological subtype of prostate sarcoma had no significant influence on actuarial survival. CONCLUSIONS: The long-term disease specific survival rate for adults with prostate sarcoma is poor. Early diagnosis and complete surgical resection offer patients the best chance for cure.     

Prognostic factors predictive of survival for truncal and retroperitoneal soft-tissue sarcoma.

OBJECTIVE: The authors identified prognostic factors relevant to clinical outcomes (especially survival) in truncal and retroperitoneal soft-tissue sarcoma. SUMMARY BACKGROUND DATA: These results can be used to optimize surgical management and select patients most likely to benefit from novel therapeutic strategies in future trials. METHODS: A retrospective analysis was performed of a prospectively compiled database of 183 consecutive patients with truncal and retroperitoneal sarcomas seen at the Brigham and Women's Hospital and the Dana Farber Cancer Institute between 1970 to 1994. RESULTS: For truncal sarcoma, multivariate analysis showed that high-grade histology was associated with an eightfold increased risk of death compared with low-grade histology (p = 0.001). In addition to grade, gross positive margin of resection (p = 0.001), microscopic positive margin (p = 0.023), and tumors greater than 5 cm in size (p = 0.018) were important independent prognostic factors for survival. In this series, postoperative radiation therapy for truncal sarcoma was associated with a 2.4-fold decreased risk of death compared with truncal sarcoma patients receiving no adjuvant radiation therapy, having adjusted for the other prognostic factors (p = 0.030). In contrast, for retroperitoneal sarcoma, multivariate analysis showed that high-grade and intermediate-grade histology were associated with a five- to sixfold increased risk of death compared with low-grade histology (p = 0.009). In addition to grade, gross positive margin of resection (p = 0.001) and microscopic positive margin (p = 0.004) were important independent prognostic factors for survival in retroperitoneal sarcoma. Patients who received either preoperative or postoperative chemotherapy for retroperitoneal sarcoma had a 4.6-fold (p = 0.002) and 3-fold (p = 0.010) increased risk of death, respectively, compared with patients receiving no adjuvant chemotherapy, having adjusted for the other prognostic factors. CONCLUSIONS: The histologic grade and the margin of resection are prognostic for survival in both truncal and retroperitoneal soft-tissue sarcoma. Tumor size was an independent prognostic factor for truncal sarcoma, but not for retroperitoneal sarcoma. Postoperative adjuvant radiation was beneficial to overall survival for truncal sarcoma. In this series of patients receiving a heterogeneous mixture of chemotherapeutic regimens-either as preoperative "neoadjuvant" therapy or as postoperative "adjuvant" therapy, there were no beneficial effects on survival compared with nonrandomized patients not receiving chemotherapy.     

Adult urological sarcoma.

From July 1982 to December 1989, 43 of 1,583 adults (2.7%) with soft tissue sarcoma admitted to the Memorial Sloan-Kettering Cancer Center (MSKCC) had tumors arising from the urinary tract and male genital tract (urological sarcoma). The most common site of origin of the tumor was paratesticular (14 patients), followed by the prostate/seminal vesicle (12), bladder (10) and kidney (7). The most common histological type was leiomyosarcoma (19 patients), followed by rhabdomyosarcoma (14), liposarcoma (5) and 5 other histological sarcoma categories (angiosarcoma, malignant fibrous histiocytoma, mesenchymoma and 2 undifferentiated sarcomas). Most of the tumors were high grade (86%) and more than half (56%) were greater than 5 cm. in diameter. A total of 9 patients (21%) presented with metastatic disease, 8 of whom had rhabdomyosarcoma. Complete resection with negative microscopic margins was possible in 58% of the patients. Actuarial relapse-free survival for all patients at 3 and 5 years was 55% and 40%, respectively. There were no significant differences in survival based on patient age, sex or histological tumor type. Favorable prognostic variables by univariate analysis included tumor diameter less than 5 cm., low histological grade, paratesticular or bladder tumor site and complete surgical resection. Application of the MSKCC sarcoma staging system, which is based on grade, size, depth and presence or absence of metastasis, was useful to predict survival. In our experience patients with stage 3 (high grade, greater than 5 cm., 15 patients) or stage 4 (metastatic disease, 9 patients) had a combined 3-year relapse-free survival rate of only 26% and they should be considered candidates for adjuvant treatment protocols.     

Prognostic factors for first recurrence in patients with retroperitoneal sarcoma

BACKGROUND: Retroperitoneal sarcomas are characterized by a high local recurrence rate despite optimal surgical treatment. The definition of prognostic factors for recurrence could help offer high-risk patients a closer follow-up and a multidisciplinary therapeutic approach. PATIENTS AND METHODS: A cohort of 40 patients treated for a primary retroperitoneal sarcoma was retrospectively analyzed. Median follow-up was 24 months. Patient (sex and age), tumor (maximal size, histologic type, tumor localization, and histologic grade), and treatment (complete vs. incomplete surgery) characteristics were included in univariate and multivariate prognostic factor analyses. RESULTS: After a median follow-up of 24 months (range 3-121), the overall recurrence rate was 65%. Median time between initial surgery and recurrence was 15 months (range 11.5-29.5). In univariate analysis, surgical positive margins (P = 0.011), bilateral tumors (P = 0.0034), nonliposarcoma histologic subtypes (P = 0.043), and a high histologic grade (P = 0.0072) were associated with an increased recurrence rate. All these factors except the histologic subtypes retained an independent prognostic value in the multivariate analysis. Death was strongly related to recurrence (P = 0.0033). CONCLUSION: The optimal treatment of patients with primary retroperitoneal sarcoma should be based on radical surgery, with en bloc organ resection if necessary, to minimize the risk of positive margins. In high-risk patients, close follow-up is mandatory to offer optimal subsequent surgical procedures. The impact of a multidisciplinary therapeutic approach remains to be proved.     

Population-based study of treatment outcomes in squamous cell carcinoma of the retromolar trigone.

BACKGROUND: Carcinoma of the retromolar trigone is relatively uncommon. High rates of local recurrence account for a relatively poor prognosis. STUDY DESIGN: A population-based historical cohort of 76 cases with biopsy-proven squamous cell carcinoma of the retromolar trigone were studied as a case series. Kaplan-Meier survival curves and log rank test were used for statistical analysis. RESULTS: The mean age was 67.2 years. Fifty-six patients were male, 45% had T1 or T2 tumors, and 61% were staged as N0. Treatment included radiotherapy in 35%, surgery alone in 26%, surgery and radiotherapy in 23%, and 16% received palliative treatment. The absolute and disease-specific survivals at 5 years were 51.4% and 67.7%, respectively. In patients treated with surgery, the resection margin status predicted the overall 5-year survival (P = .027), with 75% of patients with negative margins surviving 5 years versus a survival of 0% of patients with involved margins. CONCLUSIONS: Squamous cell carcinoma of the retromolar trigone has a poor survival rate for early-stage disease. Adequate surgical margins can improve survival.     

Radical cystectomy for the treatment of T1 bladder cancer: the Canadian Bladder Cancer Network experience

Background:

Radical cystectomy may provide optimal survival outcomes in the management of clinical T1 bladder cancer. We present our data from a large, multi-institutional, contemporary Canadian series of patients who underwent radical cystectomy for clinical T1 bladder cancer in a single-payer health care system.

Methods:

We collected a pooled database of 2287 patients who underwent radical cystectomy between 1993 and 2008 in 8 different centres across Canada; 306 of these patients had clinical T1 bladder cancer. Survival data were analyzed using Kaplan-Meier method and Cox regression analysis.

Results:

The median age of patients was 67 years with a mean follow-up time of 35 months. The 5-year overall, disease-specific and disease-free survival was 71%, 77% and 59%, respectively. The 10-year overall and disease-specific survival were 60% and 67%, respectively. Pathologic stage distribution was p0: 32 (11%), pT1: 78 (26%), pT2: 55 (19%), pT3: 60 (20%), pT4: 27 (9%), pTa: 16 (5%), pTis: 28 (10%), pN0: 215 (74%) and pN1-3: 78 (26%). Only 12% of patients were given adjuvant chemotherapy. On multivariate analysis, only margin status and pN stage were independently associated with overall, disease-specific and disease-free survival.

Interpretation:

These results indicate that clinical T1 bladder cancer may be significantly understaged. Identifying factors associated with understaged and/or disease destined to progress (despite any prior intravesical or repeat transurethral therapies prior to radical cystectomy) will be critical to improve survival outcomes without over-treating clinical T1 disease that can be successfully managed with bladder preservation strategies.