Ann Thorac Surg 2005;79:438-442
© 2005 The Society of Thoracic Surgeons
Original article: General thoracic
Immediate and Long-Term Survival After Surgery for Lung Cancer in Heart Transplant Recipients
Patrick Bagan, MD*,
Jalal Assouad, MD,
Pascal Berna, MD,
Redha Souilamas, MD,
Françoise Le Pimpec Barthes, MD,
Marc Riquet, MD
Department of Thoracic Surgery, Georges Pompidou European Hospital, Paris V University, Paris, France
Accepted for publication July 14, 2004.
* Address reprint requests to Dr Bagan, Service de Chirurgie Thoracique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75908 Paris, France (E-mail: patrick.bagan{at}hop.egp.ap-hop-paris.fr).
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Abstract
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BACKGROUND: Lung cancer observed after heart transplantation is considered to have a poor prognosis. However, the results of surgical treatment have not yet been significantly evaluated. This retrospective study analyzed the immediate and long-term results after surgery.
METHODS: From May 1990 to December 2003, 25 heart transplant recipients underwent surgery for lung cancer. There were 22 men and 3 women, the mean age was 60.7 years (49–72). All patients had a smoking history. Lung tumors were discovered by routine chest roentgenograms and computed tomography scans in 17 patients (68%), because of clinical symptoms in 7 (28%), and incidentally in 1 (4%). The surgical procedures consisted of 23 lobectomies and 2 wedge resections.
RESULTS: The mean postoperative hospital stay was 14.2 days (5–34). The morbidity rate was 28% (n = 7 patients). The mortality rate was 12% patients (n = 3 patients). The postoperative complications in 7 of 10 patients were mainly from infectious origin. Five-year survival rate was 40.9% with a median survival of 45 months. Seven patients died during follow-up (3 from cancer and 4 from other diseases). Significant better survival was observed in N0 patients than in N+ patients (median survival of 56.8 months in N0 vs 13.5 months in N+ patients (p = 0.017).
CONCLUSIONS: Long-term results after surgery were satisfactory in early stage disease, despite a high risk for postoperative infection. Our results underline the efficiency of a close follow-up for transplant recipients with a smoking history, leading to cancer detection at an early stage.
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Introduction
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The risk of neoplasia is considered to be higher in solid-organ transplant recipients than in the general population. Immunosuppressive therapy is complicated by an increased occurrence of squamous cell carcinomas of the skin, non-Hodgkin's lymphomas, and Kaposi's sarcoma [1]. Several articles recently observed an unexpectedly high incidence of bronchogenic carcinoma in heart transplant recipients (HTRs) that was associated with poor survival [2–5]. During the last 5 years, we also observed at our institution a significant incidence of HTRs who underwent surgical treatment for bronchogenic carcinoma. This retrospective study analyzed the characteristics and the outcome of these patients to determine the efficiency of surgery.
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Material and Methods
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From May 1990 to December 2003, 25 HTRs with non-small-cell lung cancer (NSCLC) were operated on in our Thoracic Surgery Department. These patients were referred by two transplantation units (Georges Pompidou Hospital and La Pitié Hospital, Paris). They represented 0.8% of the HTR population who survived more than 1 month. There were 22 men and 3 women and the mean age was 60.7 years (49–72). All recipients had a smoking history.
The cause of heart failure was an ischemic cardiomyopathy in 17 patients, valvular heart disease in 6 patients, and an idiopathic cardiomyopathy in 2 patients. Thirteen patients were treated with cyclosporine, azathioprine, and prednisone, 9 with cyclosporine and prednisone, and 3 with only cyclosporine. Nine patients had a chronic renal insufficiency because of cyclosporine, 3 patients had a chronic hepatitis C because of blood transfusion, 2 patients had a severe chronic obstructive pulmonary disease (COPD) because of smoking habits, and 1 patient had a history of prostatic carcinoma. During follow-up, chest roentgenograms were obtained at 3-months intervals and recipients with a heavy smoking history benefited from computed tomographic (CT) scans twice a year in our transplantation outpatient clinics.
Time to diagnosis after heart transplantation ranged from 2 to 180 months (mean, 88 months). Lung tumors were detected by chest roentgenograms in 13 patients (52%), by systematic CT scans in 4 patients (16%); because of clinical symptoms in 7 patients (28%) consisting of pneumonia in 4, and fever, back pain, and hemoptysis in 1 patient each; and incidentally on a preoperative evaluation for orthopedic surgery in 1 patient (4%). Six of the 7 patients who presented with clinical symptoms had endobronchial tumors that were not demonstrated by chest roentgenogram or CT scan.
The preoperative evaluation included bronchoscopy, thoracoabdominal and cerebral CT scan, pulmonary function tests, and lung perfusion scintigraphy. Mediastinoscopy was performed only to rule out N3 disease or to confirm N2 disease, if suspected on CT scan. Clinical staging was stage I (n = 22), stage IIA (n = 1), and stage IIIB (n = 2). A histologic examination was obtained preoperatively in 11 patients (bronchoscopic biopsy in 10 and transparietal biopsy in 1) and during surgery in 14 patients.
Neoadjuvant chemotherapy was administered in 2 patients (stage IIA and IIIB lung cancer) and neoadjuvant chemoradiotherapy in 1 patient (stage IIIB), with a good response to the therapy before operation.
The surgical procedures consisted of 20 lobectomies, 2 bilobectomies, 1 lobectomy associated with combined chest wall resection and vertebrectomy, and 2 wedge resections (1 patient at stage IIIB and 1 patient with palliative resection for stage IV). During the operations all patients received traditional antibiotic prophylactic therapy (intravenous cefazolin).
Details of circumstances of detection, surgical procedure, and pathologic staging are depicted in Table 1. Death from cancer or other cause was the terminal event for survival calculation; deaths within 30 days of operation were included. Data for the survival of patients were updated for December 2003. The probability of survival was calculated with the Kaplan-Meier method. Differences between survival curves were assessed by the log-rank test. All statistical analysis were performed by using computerized software (StatView, Brain Power Inc, Calabasas, CA), with a p value of less than 0.05 considered as significant.
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Results
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The mean postoperative hospital stay was 14.2 days (5 to 34). The morbidity rate was 28% (n = 7 patients). The mortality rate was 12% (n = 3 patients). Infections complications occurred in 7 of 10 patients. All postoperative complications are detailed in Table 2.
Pathologic staging was stage IA (n = 10), IB (n = 7), IIA (n = 1), IIB (n = 2), IIIA (n = 2), IIIB (n = 2), IV (n = 1). Adjuvant therapy was administered in 6 patients after operation because of metastatic lymph nodes (radiotherapy, chemotherapy, and chemoradiotherapy in 2 patients each).
The mean follow-up period for the entire study population was 40 months (range, 1 to 168 months). Follow-up was complete for all patients. During follow-up, 7 patients died. Three patients with lymph node invasion (1 at N1 and 2 at N2) died from multiple metastasis of the lung cancer. Four N0 patients died from other diseases (renal insufficiency in 2, and hepatocellular failure and pulmonary embolism in 1 patient each). Fifteen patients were alive without disease at the time of this analysis. The 5-year survival rate of the study population was 36%, with a median of survival of 39 months (Fig 1). The 2-year and 5-year survival of the 17 N0 patients was 72.2% and 44%, respectively. The survival of N0 patients was significantly better than that of the N1–N2 patients (n = 8), whose 2-year and 5-year survival rate was 14.3% and 0%, respectively (p = 0.0106) (Fig 2).
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Fig 2. Kaplan-Meier survival curves were compared based on the extension of metastasis into the lymph nodes (N0 = no metastasis; N+ = metastasis present). A statistically significant difference was observed (log-rank test; p = 0.0106).
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Comment
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Epidemiology
In the heart transplant population, the prevalence of bronchogenic carcinoma ranges from 0.6% to 4% [2–12]. The mean prevalence is 1% in the largest series [9, 12, 13]. The high incidence of lung cancer in HTRs can be explained by the augmentation of ischemic heart failure caused by tobacco consumption as the indication for heart transplantation [4, 11]. In our population, 17 of the HTRs (68%) had an ischemic cardiomyopathy as the indication for heart transplantation. In fact, the immunosuppression regimen seems to have little effect on the development of lung cancer in HTRs, contrary to the smoking history that was observed in all patients.
Postoperative Outcome
Postoperative complications were probably favored by immunosuppressive drug therapy. We observed a high rate of severe postoperative infectious complications, with lethal consequences in 2 patients (Table 2). Some authors have proposed to measure the procalcitonin plasma level to specifically detect bacterial infections in the transplant recipient, but we have not had such experience [14]. Our main concern is to decrease the higher number of sepsis in HTRs than in the general population [15]. We suggest that an earlier treatment of infection may help prevent severe postoperative complications observed in HTR. Preoperative and postoperative repeated cultures of sputum need to be performed, and careful perioperative management of antibiotic therapy must be adopted.
Prognosis and Detection
The poor prognosis of bronchogenic carcinoma after heart transplantation reported in the literature is mainly explained by the diagnosis of the lung cancer at an advanced stage of the disease [2–5]. As we calculated from different reports, 39% (31/80) of the patients benefit from complete curative resection (Table 3). This rate is superior to the 20% to 25% of operated patients in the general population [16]. According to long-term survival data available in the literature, median survival of patients who underwent curative surgical treatment was 23 months, ranging from 12 to 34 months [3, 7, 8, 9, 12, 13]. Most authors stress that survival in HTRs depends mainly on the quality of the posttranplantation surveillance [11–13]. The worst survival rate (median survival of 27 days) is observed when standard chest roentgenograms are performed at 6-months intervals during follow-up [3].
As De Perrot and colleagues suggest, we think that a careful search for bronchogenic carcinoma in recipients with a history of smoking may help improve survival [12]. We, along with others, [4, 9] have observed that standard roentgenograms miss lung cancer in 50% of patients. Regular CT scans of the chest are more appropriate for the detection of early stage lung cancer. In a previous report, one of our transplantation units noted that twice-yearly combined roentgenograms and CT scans permitted surgical treatment in 8 of 11 (72%) HTR patients with NSCLC [11].
Concerning long-term survival, deaths in N0 patients are due to consequences of transplantation and immunosuppressive drug therapy (renal insufficiency, hepatocellular failure). The cause of deaths in patients with lymph node extension (N1, N2) is cancer recurrence (n = 3). The 2-year survival in operated pathologic N+ patients (14.3%) is comparable to that reported by Pham and colleagues in non-resected clinical N+ patients (22%) [3].
The significant difference between N0 and N+ patient survival that we and other authors observed reflects the rapid evolution of bronchogenic carcinoma in immunosuppressed patients once cancer invades lymph nodes [3, 11–13]. Therefore, we suggest that positron emission tomographic scans or mediastinoscopy (or both) be included in the evaluation when lymph node involvement is suspected to rule out N+ patients who are poor candidates for surgery.
In conclusion, bronchogenic carcinoma is not a complication of immunosuppressive drug therapy. It occurs mainly in recipients with a smoking history. Nevertheless, immunosuppression regimens seem to decrease the defense against metastatic extension. Curative surgery improves survival of HTRs at an early stage of cancer despite a higher risk of postoperative infection. Our results underline the efficiency of a close follow-up in recipients with a smoking history.
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References
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Abstract
Introduction
