Does aggressive local therapy improve survival in metastatic breast cancer?

BACKGROUND: Women with metastatic breast cancer and an intact primary tumor are currently treated with systemic therapy. Local therapy of the primary tumor is considered irrelevant to the outcome, and is recommended only for palliation of symptoms. METHODS: We have examined the use of local therapy, and its impact on survival in patients presenting with stage IV breast cancer at initial diagnosis, who were reported to the National Cancer Data Base (NCDB) between 1990 and 1993. RESULTS: A total of 16,023 patients with stage IV disease were identified in the NCDB during this period, of whom 6861 (42.8%) received either no operation or a variety of diagnostic or palliative procedures, and 9162 (57.2%) underwent partial (3513) or total (5649) mastectomy. The presence of free surgical margins was associated with an improvement in 3-year survival in partial or total mastectomy groups (26% vs 35%, respectively). A multivariate proportional hazards model identified the number of metastatic sites, the type of metastatic burden, and the extent of resection of the primary tumor as significant independent prognostic covariates. Women treated with surgical resection with free margins, when compared with those not surgically treated, had superior prognosis, with a hazard ratio of 0.61 (95% confidence interval 0.58,0.65). CONCLUSIONS: These data suggest that the role of local therapy in women with stage IV breast cancer needs to be re-evaluated, and local therapy plus systemic therapy should be compared with systemic therapy alone in a randomized trial.     

Metastases of the pelvis: does resection improve survival?

Limited data are available to compare the outcome of wide en bloc resection and curettage for pelvic metastases. Previous studies have reported that curettage is associated with high mortality and decreased survival compared to wide resection and have justified consideration of a radical surgical approach to achieve pain palliation and tumor control. In this study, we aimed to evaluate the role of curettage/marginal resection compared to wide en bloc resection for patients with pelvic metastases. The hypothesis was that wide resection does not improve survival even in patients with solitary pelvic metastases.Between 1985 and 2009, twenty-one patients with pelvic metastases were treated with wide resection (12 patients) and curettage/marginal resection (9 patients) and adjuvants. Sixteen patients had solitary pelvic metastases. At a mean of 28 months (range, 2-152 months), we found no difference in survival to death or local recurrence with wide en bloc resection compared to curettage or marginal resection, even in patients with solitary pelvic metastases. The overall survival to death and local recurrence was 30% and 47% at 60 months, respectively. Survival to death of patients treated with wide resection was 18% at 60 months compared to 62% at 60 months of patients treated with curettage/marginal resection; no difference in survival to death between wide resection and curettage/marginal resection was observed even in patients with solitary pelvic metastases. Survival to local recurrence of patients treated with wide en bloc resection was 67% at 36 months compared to 26% at 36 months of patients treated with curettage/marginal resection; this was also not statistically significant. One patient treated with wide resection for a solitary pelvic metastasis had a postoperative complication.     

Liver resection for breast cancer metastasis: Does it improve survival?

Purpose To assess the outcome and prognostic factors of liver surgery for breast cancer metastasis. Methods We retrospectively examined 16 patients who underwent partial liver resection for breast cancer liver metastasis (BCLM). All patients had been treated with chemotherapy or hormonotherapy, or both, before referral for surgery. We confirmed by preoperative radiological examinations that metastasis was confined to the liver. The survival curve was estimated using the Kaplan-Meier method. Univariate and multivariate analysis were conducted to evaluate the role of the known factors of breast cancer survival. Results The median age of the patients was 54 years (range 38–68) and the median disease-free interval between the diagnoses of breast cancer and liver metastasis was 54 months (range 7–120). Nine major and 7 minor hepatectomies were performed. There was no postoperative death. The overall 1-, 3-, and 5-year survival rates were 94%, 61%, and 33%, respectively. The median survival rate was 42 months. Univariate analysis revealed that hormone receptor status, number of metastases, a major hepatectomy, and a younger age were associated with a poorer prognosis. The survival rate was not influenced by the disease-free interval, grade or stage of breast cancer, or intraoperative blood transfusions. The number of liver metastases was identified as a significant independent factor of survival according to the Cox proportional hazard model (P = 0.04). Conclusions Liver resection, when done in combination with adjuvant therapy, can improve the prognosis of selected patients with BCLM.     

Does coronary artery bypass surgery improve survival?

Abstract Objectives. According to guide-lines, coronary bypass surgery improves survival in high risk patients. The evidence for this is more than 20 years old and may be questioned. Long waiting lists for coronary bypass surgery are detrimental but offer the possibility to compare the risk of death before and after surgery. We hypothesized that the risk of death is lower after bypass surgery than before the operation in high risk patients in a more recent cohort. Design and results. Death hazard functions were calculated by the use of Poisson regression scheduled for bypass surgery between 1 Jan 1995 and 31 July 2005. The analyses were performed in two states: 1) in the period after triage until admission for surgery during which optimal medication was intended and 2) after surgery and up to 11 years (corresponding to 57,548 patient years). The probability of death was calculated by entering individual risk profile data into the two multivariable functions. There were several significant differences between the hazard functions in the two states. All variables reflecting angiographic severity of coronary lesions indicated lower risk of death after bypass surgery. The risk associated with left ventricular impairment was lower after surgery (beta coefficients - 0.0546 vs. - 0.0234, p <0.001). Only one variable, age, indicated higher risk after surgery (which is also seen in a general population over time). The reduction of risk was dependent on preoperative risk with a large reduction when preoperative risk was high and vice versa. When preoperative risk was low, however, the risk increased due to surgical mortality. Conclusions. The risk of death is lower after bypass surgery than before the operation in high risk patients. This is most likely explained by a prognostic gain from bypass surgery. The gain is largest in high-risk patients but small or absent in low risk patients.     

Does surgical debulking for advanced stages of thymoma improve survival?

A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Does surgical debulking for advanced stages of thymoma improve survival?' Altogether, only 17 papers were found using the reported search, of which only 10 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated; these studies have mainly reported the survival and recurrence rates after total vs subtotal resection of thymic tumours in patients receiving or not receiving adjuvant chemoradiotherapy. These studies confirmed that complete resection is the best prognostic factor in thymomas. With regard to subtotal tumour resection/debulking, we did not find any randomized controlled trials. The evidence on this topic is scarce and these 10 reported were retrospective reviews of the operative, histology and survival data of patients with thymoma who had subtotal vs partial resection for advanced stages of thymoma. Although debulking surgery for thymoma had positively affected survival, in six studies, the difference failed to reach statistical significance. Three of the studies, on the other hand, showed a higher survival rate in thymomas in which maximum debulking was performed and the treatment was followed by high-dose irradiation. None of these studies showed any benefit in debulking surgery for thymic carcinoma. Besides histology and tumour cell-type, other factors influencing survival included the tumour stage and the presence of symptoms such as myasthenia gravis as a warning sign at an early stage. Current evidence in the literature on the survival after debulking surgery for thymoma is contradictory, and most of the studies do not show any survival benefit after debulking for thymoma. However, debulking surgery minimizes the tumour size and area for irradiation postoperatively, hence it can result in less damage to the adjacent tissue during radiotherapy and may be considered for patients in advanced stages of thymoma in whom extensive radiotherapy will be required. In these cases, however, the risks of surgery followed by radiotherapy or radiotherapy alone should carefully be assessed prior to the initiation of treatment.     

Should lobectomy patients with microscopic involvement of the bronchial resection margin undergo re-operation to improve their long-term survival?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether re-operative surgery or radiotherapy should be given to patients with residual microscopic tumour at the bronchial resection margin. Altogether 427 papers were identified using the reported search of which 13 represented the best evidence on this topic. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses were tabulated. We conclude that for patients with stage I-II tumours who could easily tolerate re-operation, further resection is an acceptable treatment option and may improve survival. However, only 4 of the 13 studies that we identified recommend this strategy. In addition, there is no convincing evidence that radiotherapy significantly improves survival for patients not selected for re-operation.     

Does endogenous immune response determine the outcome of surgical therapy for metastatic melanoma?

Background Although the presence of tumor cells in the blood of patients with metastatic melanoma suggests widely disseminated disease many of these patients enjoy prolonged survival or cure after surgical resection. Our previous study of adjuvant vaccine therapy after complete resection of metastatic melanoma revealed a strong correlation between postoperative survival and elevated antibody titers to a 90-kDa tumor-associated antigen (TA90) expressed by melanoma cells of the vaccine. We hypothesized a similar correlation between postoperative survival and endogenous anti-TA90 antibody titers induced by the patient’s melanoma in the absence of postoperative adjuvant immunotherapy. Methods From 1970 to 1996, 64 patients underwent complete resection of distant melanoma metastases and did not receive postoperative adjuvant immunotherapy. Serum collected within 4 months after surgery was tested in a coded and blinded fashion for anti-TA90 IgG and IgM by enzyme-linked immunosorbent assay, and for total IgG and IgM (controls) by radial immunodiffusion. Results Median follow-up for the study population was 19 months (range, 3–147 months). There was no significant correlation between anti-TA90 IgG titer and total IgG level (P=.4785), or between anti-TA90 IgM and total IgM (P=.0989). Univariate analysis showed that postoperative anti-TA90 IgM titer as a continuous variable was significantly associated with overall survival (OS); i.e, the higher the anti-TA90 IgM titer, the longer the OS. Using an established cutoff titer of 800, median OS was 42 months for patients with high anti-TA90 IgM titer (n=28) vs. 9 months for patients with low titers (n=36) (P=.0001). There was no significant correlation between total IgG/IgM and survival (P=.4107 and .4044, respectively). Multivariate, analysis identified anti-TA90 IgM as the most significant independent variable influencing OS after complete resection of distant melanoma metastases (P-.0001). Conclusions We conclude that the endogenous immune response to metastatic melanoma determines the outcome after surgical therapy. Enhancement of this specific immune response may prolong the survival of patients with distant melanoma metastases. Presented at the 52nd Annual Meeting of the Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Does radical resection improve the survival in patients with carcinoma of the gallbladder who are 75 years old and older?

Radical resections have been reported to improve the surgical outcome for patients with carcinoma of the gallbladder. In recent years surgeons have had more opportunities to operate on elderly patients. We investigated whether the survival rate of aged patients who had radical resections were better than rates for those who had simple cholecystectomy. Of the 300 patients treated for carcinoma of the gallbladder between 1971 and 1999, 206 resected cases (except pancreaticoduodenectomy and hepatectomy) were divided into two groups: age 75 years or older, 54 patients (the older group), and age less than 75 years, 152 patients (the younger group). Clinical features and progression of the carcinomas did not differ between the two groups. In the older group, 22 patients (40.7%) had simple cholecystectomy, 32 (59.3%) had radical resections; in the younger group, 65 patients (42.8%) had simple cholecystectomy, and 87 (57.3%) had radical resection. None of the older patients who had radical resection died postoperatively. Postoperative survival was not different between the two groups. In the older group the 5-year survival rate for patients who had radical resections was better (60.9%) than the rate for those who had simple cholecystectomy (14.1%) (p = 0.0098). Radical resection is effective for the aged patients with the carcinoma of gallbladder.     

Does a concomitant Cox-maze procedure improve survival in atrial fibrillation?

In this review paper, the authors briefly describe the pathophysiology of atrial fibrillation. The original technique to restore sinus rhythm is cited, with its subsequent technical variations. A literature review summarizes the outcome of patients who benefited from the Cox-MAZE procedure.     

Does lung cancer screening with chest X-ray improve disease-free survival?

A best evidence topic in thoracic surgery was written according to a structured protocol. The question addressed was whether screening an asymptomatic person with a routine chest X-ray would detect lung cancer early and, most importantly, improve that person's disease-free survival from lung cancer. Altogether 136 papers were identified using the search below. Ten papers presented the best evidence to answer the clinical question. The author, journal, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of the papers are tabulated. We conclude that despite methodological criticisms and concerns regarding biases inherent to screening studies, there is currently no evidence to support the use of chest X-ray to screen an asymptomatic person for lung cancer.     

Does primary melanoma of the bladder exist?

Primary melanoma of the urinary bladder is a rare neoplasm to which very strict diagnostic criteria apply. Although reports of previous cases exist, these criteria have yet to be met. We report a case of a young lady from whom a malignant melanoma of the bladder was resected. This was presumed to be primary as detailed investigation failed to find any other site from which metastases could have originated. We discuss the diagnostic criteria of this entity and stress the difficulty in conclusively demonstrating that, despite some of these criteria being met, a lesion such as this is primary in origin. This case could be the longest surviving patient with primary melanoma of the bladder, however we will never be able to prove that spontaneous regression of an undiagnosed extravesical primary malignant melanoma did not occur.     

Does early cystectomy improve the survival of patients with high risk superficial bladder tumors?

PURPOSE: We compared survival after early versus delayed cystectomy in patients with high risk superficial bladder tumors. MATERIALS AND METHODS: Of 307 patients with high risk superficial bladder tumors who were treated initially with transurethral resection and bacillus Calmette-Guerin (BCG) therapy 90 (29%) underwent cystectomy for recurrent tumor during a followup of 15 to 20 years. Disease specific survival distribution of these 90 patients was determined relative to the indications for and time of cystectomy. RESULTS: Of the 90 patients who underwent cystectomy 44 (49%) survived a median of 96 months. Of 35 patients with recurrent superficial bladder tumors 92% and 56% survived who underwent cystectomy less than 2 years after initial BCG therapy and after 2 years of followup, respectively. Of 55 patients with recurrent muscle invasive bladder disease 41% and 18% survived when cystectomy was performed within and after 2 years, respectively. Multivariate analysis showed that survival was improved in patients who underwent earlier rather than delayed cystectomy for nonmuscle invasive tumor relapse. CONCLUSIONS: Earlier cystectomy improves the long-term survival of patients with high risk superficial bladder tumors in whom BCG therapy fails.     

Removal of primary tumor improves survival in metastatic breast cancer. Does timing of surgery influence outcomes?

Background

Resection of intact primary tumor is controversial in metastatic breast cancer patients. The aim of this study is to review the impact of surgical resection of primary tumor on overall survival and to assess the role of timing of surgery on survival rates.

Methods

208 patients with metastatic breast cancer diagnosed between 1982 and 2005 in the Hospital Clinico of Valencia (Spain) were analysed. Exclusion criteria were age >80, PS 3–4, Charlson score 3 or follow-up < 90 days. 123 of these underwent surgery and 85 did not. In order to assess the role of timing, the "surgery" cohort was divided into two sub-groups: "before" (n = 78) or "after" (n = 45) diagnosis of disseminated disease.

Results

In the surgery group, patients underwent mastectomy with axillary dissection (82.9%), without axillary dissection (8.9%) and conservative surgery (8.1%). After a median follow-up of 29.68 months, median OS in the "surgery" and the "non-surgery" groups were, 40.4 and 24.3 months. Removal of the primary tumor therefore had a significant positive impact on survival rates (p < 0.001). Benefits of surgery were observed mainly in patients with visceral disease (p = 0.005); no statistical differences were found in those with bone disease (p = 0.79). Univariate analysis for overall survival (OS) identified surgery, performance status, clinical T stage, hormone receptors and number and type of metastases as variables that impacted on survival. In the multivariate test, only resection of primary tumor and estrogen receptors maintained statistical significance, surgery having a protective effect with an HR 0.52 (95% CI 0.35–0.77). No differences in survival were found between the two sub-groups according to the timing of surgery: "before" vs "after"(p = 0.996).

Conclusions

Resection of primary tumor should be considered not only as a palliative or preventive strategy but also as an approach that possibly contributes to the control of the disease in selected patients.