Additional pulmonary resections after pneumonectomy: actual long-term survival and functional results

Transcription

1 European Journal of Cardio-thoracic Surgery 34 (2008) Additional pulmonary resections after pneumonectomy: actual long-term survival and functional results Abstract Tomasz Grodzki *, Jacek Alchimowicz, Anna Kozak, Bartosz Kubisa, Jarosław Pieróg, Janusz Wójcik, Michał Bielewicz, Dominika Witkowska Pomeranian Medical University, Thoracic Surgery Department of the Regional Hospital for Lung Diseases, Sokołowskiego str 11, PL Szczecin Zdunowo, Poland Received 4 February 2008; received in revised form 3 May 2008; accepted 19 May 2008; Available online 25 June 2008 Objective: Pulmonary resections after pneumonectomy due to metastases or metachronous non-small cell lung cancer (NSCLC) are rare because of the high potential risk of the second procedure and uncertain long-term results. On the basis of our series (largest in Europe) we tried to assess the long-term survival of patients treated in stage IV NSCLC. Methods: Retrospective analysis was carried out on 18 patients treated at our department by pneumonectomy followed by additional resection in the years (15 males and 3 females, years, mean 57). Eleven pneumonectomies were performed on the right side and seven on the left. Twelve squamous cell carcinomas and six adenocarcinomas were diagnosed. All patients were staged postoperatively as IIB IIIA (four were N2). Their WHO status ranged between 0 and 1. The second surgical procedure (16 wedge resections, 2 chest wall resections) was performed months later (mean 26). The patients staged N2 were radiated postoperatively. Results: There were no early postoperative deaths. The morbidity rate after second surgery was comparable to that observed after ordinary wedge resection. Histology of the lesions removed during the second operation was the same as after pneumonectomy in all patients. The pulmonary function tests (PFT) results worsened significantly but still reached 56 63% of the predicted values. Sixteen resected tumors of the remaining lung were staged T1 (<3 cm), 2 T3 (<3 cm but infiltration of the parietal pleura on an area of 2 4 cm 2 ). Three patients revealed N2 disease (they were all N0 after pneumonectomy). All patients were considered M1 after second surgery. WHO status after the second procedure remained the same in 8 patients (44%) and worsened in 10 patients (56%). The survival rates were as follows: 11 patients survived 2 years (61%) while 8 patients survived 5 years (44%). The majority of patients died due to lung cancer (70%) but all the rest (30%) due to circulatory or respiratory insufficiency. There was a significant difference ( p < 0.05) in 5-year survival for N0 N1 vs N2 status (63% vs 14% 1 patient) and also regarding the time interval between surgeries: less than 12 months vs more than 12 months (0% vs 63%). Conclusions: Pulmonary resections performed after pneumonectomy due to NSCLC are rare procedures but with an acceptable perioperative risk. The second procedure should be limited to wedge resection. The prognosis is poor for patients with N2 status and for those treated by second surgery earlier than 12 months after the first procedure. # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. Keywords: Lung cancer; Pneumonectomy; Additional pulmonary resection; Long-term survival 1. Introduction The early reports on resections for lung cancer on a single remaining lung after previously performed pneumonectomy are dated in the 1950s [1,2]. Nevertheless, this type of surgery is rare in common thoracic practice (in our department it was just 0.3% of all surgeries performed in the years ). Less than 100 cases were reported in the literature up to now. The largest world series of 24 patients was published by Donington et al. from the Mayo Clinic in 2002 [3]. European papers include 14 patients reported by Terzi et al. in 2004 and 13 patients by Spaggiari et al. in 1996 [4,5]. There is a great deal of uncertainty regarding surgical mortality and morbidity in this group of patients; their functional results as well as long-term survival rate. Many physicians consider resection of a lesion in the remaining lung contraindicated. The purpose of our report on the largest European series was to present our experience of subsequent resection for lung cancer after pneumonectomy with particular attention to long-term survival rate and functional results. Presented at the 15th European Conference on General Thoracic Surgery, Leuven, Belgium, June 3 6, * Corresponding author. Tel.: ; fax: address: grodzki@grodzki.szczecin.pl (T. Grodzki). 2. Material and methods Between January 1, 1981 and September 30, 2002, 18 patients were treated at our department by subsequent /$ see front matter # 2008 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved. doi: /j.ejcts

2 494 T. Grodzki et al. / European Journal of Cardio-thoracic Surgery 34 (2008) resection of the lung cancer involving the contralateral lung remaining after previously performed pneumonectomy due to non-small cell lung cancer (NSCLC). These amounted to 0.3% of all lung tissue resections performed at our department during that time. At the same time 82 patients with lung cancer detected in the remaining lung after pneumonectomy were refused surgery for three reasons: due to symptoms of dissemination of the disease, due to central localization of the tumor in the contralateral lung or due to functional contraindications (poor reserve). Our acceptance rate of patients with lung cancer in the contralateral lung after previously performed pneumonectomy was 18%. The files of these patients were analyzed for age, sex, pulmonary function, tumor nodulus metastatis (TNM) status, WHO status, time interval between surgeries, early (within 30 days after operation) or late mortality and perioperative morbidity. Survival was estimated by the Kaplan Meier method using the date of the pulmonary resection after pneumonectomy as the starting point and the date of death as the end-point [8]. The log-rank test was used to compare survival curves. The pulmonary function tests (PFT) results were expressed as mean SD and were compared by means of the Tukey HSD test. Statistical tests were considered significant if p was less than The analysis was performed by using the Statistica 7.1 (StatSoft Inc. Tulsa, OK, USA) software. No patients were lost from follow-up. Our department is the single regional center for thoracic surgery so all patients treated surgically are controlled on site. Additionally, our assistants consult three local pulmonology centers treating our patients postoperatively so it enables the follow-up system to be tightly maintained. All lesions in the remaining lung were detected in the asymptomatic phase during regular follow-up after pneumonectomy based on repeated chest X-rays (every 3 months during the first 2 years after pneumonectomy, every 6 months during the next 3 years and annually afterwards). Preoperative examinations before surgery of the contralateral lung included: CT, sonography, echocardiography, spirometry based on forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and maximal voluntary ventilation (MVV) with exercise testing in borderline patients, bronchofiberoscopy, brain CTand/or bone scintigraphy if necessary (in case of any kind of skeletal pains or complaints) and routine preoperative lab tests. Fifteen patients (83%) underwent fine needle aspiration biopsy (FNAB) of the lesion; 14 (77%) were confirmed preoperatively as lung cancer of the single remaining lung. All others were confirmed intraoperatively. PFT were measured before pneumonectomy, before second resection and 5 6 months after second resection during a control visit. Patients were considered eligible for resection following previously performed pneumonectomy if their PFT exceeded 40% of the predicted values (according to Morris Koski tables for adult population), WHO status was O or 1, CT did not reveal mediastinal lymph nodes larger than 10 mm, bronchofiberoscopy did not reveal signs of intrabronchial malignancy, echocardiography did not indicate symptoms of pulmonary hypertension or right ventricle hypertrophy and there was no detectable extrathoracic disease. Only single peripheral lesions with intention for wedge resection were accepted for surgery; necessity of two or more wedge resections was an exclusion criterion. Exercise test (treadmill) was considered normal if the patient was able to maintain workload equivalent of 100 W for 3 min without exceeding 85% of the predicted heart rate (in accordance with Bruce protocol). PET or PET/CT was not available in Poland at the time of the study ( ). Mediastinoscopy was not performed because all patients did not reveal enlarged mediastinal lymph nodes >1 cm on CT scans. Pneumonectomy was always performed through posterolateral incision with standard mediastinal lymphadenectomy. The bronchial stump was sutured manually by Klinkenbergh modification. No drain was placed in the postpneumonectomy cavity. Intensive rehabilitation was applied from the first postoperative day. At the time of the second surgery performed using the contralateral postero-lateral approach (incision was usually shorter than for pneumonectomy and was 7 12 cm long) anesthesia was based on single lumen tube intubation with FiO % ventilation. The last two patients were ventilated with support of jet ventilation. Cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) was ready to use on site if necessary. The lung was kept in at least a semi-inflated position. Surgical technique was typical for wedge resection with use of surgical staplers. Lymph node sampling was performed in every case. A single drain was placed in a standard manner from the apex to VIIth intercostal space in mid-axillary line. Postoperative care was typical for wedge resection with special attention to potential respiratory and circulatory insufficiency. All patients were extubated at the operating theatre and intensively rehabilitated from the first hours after surgery. 3. Results All patients were treated by wedge resection not larger than single segmentectomy. Additionally, two patients had the 5 cm of single rib (4th and 6th) resected due to suspicion of chest wall invasion confirmed postoperatively (described as parietal pleura infiltration on an area of 2 4 cm 2 ). There were no early postoperative deaths. There was no need to use CPB or ECMO at the time of surgery. No differences were observed in the postoperative period in patients treated previously by right or left pneumonectomy. Clinical data of the patients are presented in Table 1. Patients with pn2 disease after pneumonectomy received radiotherapy 60 Gy 4 6 weeks after surgery. All four patients verified postoperatively as N2 presented micrometastases only in station 4 or 5; station 7 was always negative. Their preoperative CT before pneumonectomy did not reveal mediastinal lymph nodes >1 cm. They were subjected to additional resection because the control CT before second surgery did not reveal any enlarged mediastinal lymph nodes as well. The sampling during wedge resection was negative (obviously the mediastinal lymph nodes were taken from the opposite site). Additionally, three more patients revealed N2 disease at the time of second surgery on the contralateral lung. They were all staged pn0 after pneumonectomy. Two of them were subsequently radiated 54 Gy, one refused radio-

3 T. Grodzki et al. / European Journal of Cardio-thoracic Surgery 34 (2008) Table 1 Characteristics of 18 patients Number of patients 18 (15M, 3F) Age (years) (mean 57) Pneumonectomy side 11 right, 7 left Time interval between surgeries months (mean 26) Type of additional resection 16 wedge, 2 wedge + chest wall ptnm status after pneumonectomy 10 IIB, 8 IIIA pn status after pneumonectomy 14 N0 N1, 4 N2 pn status after additional resection 11 N0 N1, 7 N2 Histology after pneumonectomy 12 squamous cell ca, 6 adenoca Histology after additional resection 12 squamous cell ca, 6 adenoca Mean spirometry before pneumonectomy FEV1 97% (20%), FVC 93% (17%), MVV 99% (16%) Mean spirometry after pneumonectomy FEV1 63% (14%), FVC 61% (15%), MVV 68% (24%) Mean spirometry after additional resection FEV1 56% (13%), FVC 56% (12%), MVV 63% (15%) WHO status before pneumonectomy 0 18 pts WHO status after pneumonectomy 0 15 pts, 1 3 pts WHO status after additional resection 0 8 pts, 1 7 pts, 2 3 pts FEV1, forced expiratory volume in 1 s; FVC, forced vital capacity; MVV, maximal voluntary ventilation. Presented as % of the predicted value SD (standard deviation). therapy due to personal reasons. Consulting oncologist did not recommend chemotherapy because of the potential risk of side effects for the patients with less than one lung remaining and suggested chemotherapy in case of recurrence only. Four out of seven (57%) patients who died due to cancer relapse received chemotherapy at the time of detected recurrence, three out of seven (43%) were assessed not eligible for this therapy by oncologists. Histology of the lesions removed during second operation was the same as after pneumonectomy in all patients. Morbidity after second surgery was minor and comparable to the situation after wedge resection in patients with both lungs intact (Table 2). WHO status after additional resection remained the same in 8 (44%) patients and worsened in 10 (56%) but only 3 (16.5%) patients were assessed as WHO 2. PFT values deteriorated both after pneumonectomy and after additional resection (Figs. 1 3). The decrease of the PFT values was greater after pneumonectomy then after second resection but nevertheless all differences were significant for all three parameters (FVC, FEV1, MVV). The mean observation time for eight living patients was 141 months. The mean survival time for all those who died was 33 months. It was slightly longer for patients who died due to cardiovascular disorders but the difference was not statistically significant. The overall actual survival is presented in Fig. 4. Overall actual 2-year survival was 61% and 5-year survival reached 44%. Seven patients (70% of all deaths) died due to cancer progression. All others (three patients) died due to circulatory or respiratory insufficiency. One patient died due to exacerbation of the coronary arteries disease 49 months Fig. 1. Evolution of FEV1 after pneumonectomy and additional resection of the contralateral lung. Table 2 Complications after second surgery Complication Number of patients (%) Prolonged air leak >7 days 2 (11) Prolonged wound healing 1 (5.5) Sputum retention (treated by bronchial aspiration) 2 (11) Post-thoracotomy pain syndrome >6 months 1 (5.5) Atrial fibrillation 1 (5.5) Fig. 2. Evolution of FVC after pneumonectomy and additional resection of the contralateral lung.

4 496 T. Grodzki et al. / European Journal of Cardio-thoracic Surgery 34 (2008) Fig. 3. Evolution of MVV after pneumonectomy and additional resection of the contralateral lung. Fig. 4. Survival rate for the entire group (Kaplan Meier survival curve). after second surgery, one due to cerebral stroke 19 months after wedge resection and one due to exacerbated symptoms of cor pulmonale 89 months after second surgery. They were all N0 at the time of both surgeries. There was significant difference in the survival rate between patients with N0 N1 disease and those with N2 disease. Sixty-three percent (7 out of 11 patients) with N0 N1 disease survived 5 years or more vs 14% (1 out of 7 patients) with N2 disease (Fig. 5). There was also a strongly significant difference ( p < 0.004) in survival between patients treated by both surgeries in an interval shorter than 12 months (mean survival time 19 months) and patients treated after an interval longer than 12 months (mean survival time 89 months) (Fig. 6). Fig. 5. Long-term survival rate for N0 N1 vs N2 patients (Kaplan Meier survival curves compared). becomes more complicated if the previous surgery was pneumonectomy, which usually has a significant negative impact on pulmonary reserve. Many specialists still consider pneumonectomy as an absolute contraindication for subsequent additional pulmonary resection despite papers published by Donnington et al., Terzi et al. and Spaggiari et al. where a relatively good survival rate was presented [3 5]. Donnington reported a 40% 5-year survival rate in a group of 24 patients, Terzi achieved 30% 5-year survival in a group of 14 patients. Spaggiari limited observation to 3 years and reported 46% 3-year survival. This group of patients is considered prone to other malignancies; there are reports about incidence ranging from 1% to 4% per patient year to 25% of patients developing secondary primary tumor [10,11]. We have to keep in mind that those patients are staged IV by TNM system, so 5-year survival much beyond 3 7% should be considered above expectations but from the other side there are reports criticizing current TNM staging underestimating patients prospects for long-term survival after radical 4. Discussion Surgery for stage IV NSCLC is generally contraindicated with few exceptions for single metachronous or metastatic lesion in the central nervous system, adrenal gland or contralateral lung. The reason for this conservative approach is predominantly poor long-term survival [7]. The risk of developing new lung cancer for patients after complete resection is approximately 5 10% [9]. The situation Fig. 6. Long-term survival regarding interval between surgeries (Kaplan Meier survival curves compared).

5 T. Grodzki et al. / European Journal of Cardio-thoracic Surgery 34 (2008) resection [12,13]. Particularly, patients with solitary metastasis in the contralateral lung, brain or adrenal gland benefit from surgical resection and/or chemoradiotherapy, achieving long-term survival ranging from 20% up to 40% [3,14 16]. The American College of Chest Physicians (ACCP) in its guidelines issued in 2007 recommends resection of the solitary metastatic disease in the brain or adrenal gland in selected patients [17]. We focused our study on both actual long-term survival and functional results. According to the literature, long-term survival of patients previously treated by pneumonectomy is better if the second resection is limited to solitary wedge excision vs segmentectomy, multiple wedge or lobectomy [3]. There is a trend towards better survival for metachronous vs metastatic disease, however the above authors admit that it is difficult if not impossible to differentiate preoperatively whether the lesion is a metastatic tumor or a metachronous primary cancer [3,5]. The criteria of differences between these two cancers described by Martini (a lesion should be considered metachronous when the cell type of two lesions is different, the time interval between the two lesions exceeds 2 years and there are no other distant metastases) are somehow arbitrary and cannot serve as ultimate criterion [6]. In our series the mean interval time between surgeries exceeded 2 years (26 months) and in some cases was as long as 106 months so we should consider lesions as metachronous primary cancer rather than metastases. The second criterion regarding cell type suggests metastasis because the histology of the second lesion was always the same as the first one which is typical for metastatic tumors. Regarding the third criterion of long-term survival rate, our actual 5-year survival (44%) suggests metachronous rather than a metastatic nature of the second lesion. We have to remember that in the period our acceptance rate for second surgery was only 18% for this particular group of patients. Careful selection of potential candidates for remaining lung surgery with special attention to functional respiratory and cardiovascular reserve resulted in good early postoperative results (0% early mortality) and seems crucial for long-term beneficial effect. We consider it necessary to perform at least PFT, standardized exercise test and echocardiography in all candidates for this borderline surgery. We have found two predictors of poor prognosis: N2 status (14% 5-year survival rate vs 63% for N0 N1 patients) and the time interval between surgeries shorter than 12 months; mean survival time was 19 months vs 89 months for patients with a time interval longer than 12 months. We tried to obtain cytological diagnosis before the second operation to avoid surgery for small cell cancers, therefore the majority of our group (15 patients, 83%) underwent FNAB and 14 (77%) of them were confirmed preoperatively. Three of them (20%) presented hemoptysis after FNAB which resolved spontaneously while two (13%) experienced iatrogenic small pneumothorax (distance from the lung to the chest wall 1 2 cm) of the single lung. Both patients did not require drainage and we treated it as a kind of prognostic factor and proof of good pulmonary reserve. All our patients were in good physical condition and had suitable pulmonary reserve. PFT after pneumonectomy decreased significantly in comparison to the pre-pneumonectomy values but still ranged between 61% and 68% of predicted values (based on Morris Koski tables). They also decreased significantly again after the second procedure despite its limited nature (wedge resection) and ranged between 56% and 63% of predicted values. This is unusual if the wedge resection is performed in a patient with both lungs intact. It confirms the thesis that limited resection of the contralateral lung after pneumonectomy has a negative impact on pulmonary reserve comparable to this achieved after lobectomy in patients with both lungs. We strongly agree with suggestions by Donnington et al. that limited resection should be the method of choice for lesions of the single lung remaining after pneumonectomy. WHO status of the patients decreased more frequently after the second procedure than after pneumonectomy. It suggests that good physical status after non-complicated pneumonectomy followed by proper rehabilitation is fragile and sensitive to additional stress. Usually wedge resection does not influence physical status significantly while wedge resection after pneumonectomy decreases WHO status in the majority of patients. However, these changes are not dramatic and usually move the patients only one grade down. Selecting patients with good pulmonary reserve and excluding patients with dissemination of the disease as well as meticulous surgical manipulation and intensive perioperative rehabilitation seem to be the best guarantee of a positive long-term result. We can conclude that additional pulmonary resections performed after pneumonectomy due to NSCLC are rare procedures but with an acceptable perioperative risk. These interventions are surgically possible. However, the second procedure should be limited to wedge resection. The prognosis is poor for patients with N2 status and for those treated by second surgery earlier than 12 months after the first procedure. References [1] Rzepecki W. Is partial pulmonary resection after contralateral pneumonectomy in pulmonary tuberculosis feasible and indicated? Acta Med Pol 1960;1: [2] Wodała E, Sedlaczek A. Następowe wycięcie płuca po uprzednim drugostronnym wycięciu tkanki płucnej z powodu gruźlicy. Pol Przegl Chir 1969;41: [3] Donington JE, Miller DL, Rowland CC, Deschamps C, Allen MS, Trastek VF, Pairolero PC. Subsequent pulmonary resection for bronchogenic carcinoma after pneumonectomy. Ann Thorac Surg 2002;74: [4] Terzi A, Lonardoni A, Scanagatta P, Pergher S, Bonadiman C, Calabro F. Lung resection for bronchogenic carcinoma after pneumonectomy: a safe and worthwhile procedure. Eur J Cardiothorac Surg 2004;25: [5] Spaggiari L, Grunenwald D, Girard P, Baldeyrou P, Filaire M, Dennewald G, Saint-Maurice O, Tric L. Cancer resection on the residual lung after pneumonectomy for bronchogenic carcinoma. Ann Thorac Surg 1996;62: [6] Martini N, Melamed M. Multiple primary lung cancers. J Thorac Cardiovasc Surg 1975;70: [7] Mountain CF. Revisions in the international system for staging lung cancer. Chest 1997;111: [8] Kaplan E, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958;53: [9] Pairolero PC, Williams DE, Bergstrahl EJ, Piehler GM, Bernatz PE, Payne WS. Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984;38: [10] Rice D, Kim HW, Sabichi A, Lippman S, Lee JJ, Williams B, Vaporciyan A, Smythe WR, Swisher S, Walsh G, Putnam JB. The risk of second primary tumors after resection of stage I non-small cell lung cancer. Ann Thorac Surg 2003;76:

6 498 T. Grodzki et al. / European Journal of Cardio-thoracic Surgery 34 (2008) [11] Duchateau CS, Stokkel MP. Second primary tumors involving non-small cell lung cancer: prevalence and its influence on survival. Chest 2005;127: [12] Vansteenkiste JF, De Belie B, Deneffe GJ, Demedts MG, De Leyn PR, Van Raemdonck DE, Lerut TE, Leuven Lung Cancer Group. Practical approach to patients presenting with multiple synchronous suspect lung lesions: a reflection on the current TNM classification based on 54 cases with complete follow-up. Lung Cancer 2001;34: [13] Battafarrano RJ, Force SD, Meyers BF, Bell J, Guthrie TJ, Cooper JD, Patterson GA. Benefits of resection for metachronous lung cancer. J Thorac Cardiovasc Surg 2004;127: [14] Lucchi M, Dini P, Ambrogi MC, Berti P, Materazzi G, Miccoli P, Mussi A. Metachronous adrenal masses in resected non-small cell lung cancer patients: therapeutic implications of laparoscopic adrenalectomy. Eur J Cardiothorac Surg 2005;27: [15] Mercier O, Fadel E, Mussot S, Fabre D, Chataigner O, Chapelier A, Dartevelle P. Is surgery required for patients with isolated adrenal metastasis of non-small cell lung carcinoma? Presse Med 2007; 36: [16] Mintz A, Perry J, Spithoff K, Chambers A, Laperriere N. Management of single brain metastasis: a practice guideline. Curr Oncol 2007;14: [17] Shen KR, Meyers BF, Larner JM, Jones DR, American College of Chest Physicians. Special treatment issues in lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest 2007;132(3 Suppl.): 290S 305S.