Anales de la RANM

18 A N A L E S R A N M R E V I S T A F U N D A D A E N 1 8 7 9 TRATAMIENTO NEOADYUVANTE DEL CÁNCER DE PULMÓN Mariano Provencio Pulla An RANM · Año 2019 · número 136 (01) · páginas 17 a 24 around 40% advanced (3) disease. The cure is unlikely in patients with NSCLC and locally advanced stage who are not surgical candidates, with a 3-year survival rate of 27% in those patients receiving chemotherapy and concomitant radiotherapy (4). On the contrary, in localized stages (stage I, II, IIIA) with surgical resection and cytostatic therapy, a survival of 5 years of 51% (5) is achieved and those with an absolute benefit in survival at 5 years of 5.4%, especially in patients with good performance status (PS) (6). At diagnosis, at least 40% of patients are diagnosed at an advanced stage and a third locally advanced disease (stage III). We understand as locally advanced disease when the tumor exceeds the lung structures, but without clinical evidence of distant spread, and are a very heterogeneous group of patients with a controversial treatment based on a combination of surgery, chemotherapy and radiotherapy. In the past, radiation therapy was considered standard therapy for patients with stage IIIA and IIIB but presented poor survival with poor local control and early development of distant disease. Patients with inoperable stage III treated with chest radiation therapy alone, had a median survival of 11.9 months, survival at 2 years of 10-20% and 3 years 5-10% (7). Currently, there is no consensus on the best standard treatment and it has been demonstrated that the experience of the therapeutic team plays an important role in the decisions to take. Only 25-30% of the NSCLC are candidates for curative-intent surgery. The rest are advanced local tumors or widespread metastases. Survival at 5 years depends, among other factors, on the size of the tumor and lymph node involvement. But even without mediastinal involvement, less than half of the patients survive more than 5 years and the majority dies of disseminated metastases. Patients with stage IIIA disease with clinically evident N2 nodal spread have an overall 5-year survival rate of only 10%-15%, although this fall to 2%-5% in those with bulky mediastinal N2 involvement. The surgical management of stage IIIA NSCLC remains highly controversial and most patients with stage IIIB disease are generally considered inoperable. The aims of therapy in stage III NSCLC are to increase both locoregional and systemic control of the disease. As a matter of fact, it is reported that at least 80% of patients treated with local modalities alone will have micrometastases and will relapse. These aims could in some way be in conflict and may require different combined modality therapy sequencing strategies. Success in achieving them is measured in time of progression, survival and cure rate. Strategies that have been investigated include induction chemotherapy, concomitant chemoradiotherapy, intensified radiotherapy and adjuvant treatment. Since distant metastases remain the major site of failure, it is likely that more effective cytotoxic or other anti-tumor agents will be required further to improve current levels of response and survival (8). Meta- analysis has suggested that cisplatin-based induction chemotherapy prior to surgery reduces risk of death by 13 % and increased absolute 5-year survival rates by 5% (9). Neoadjuvant therapy has theoretical advantages: in vivo assessment of response to chemotherapy helps identify patients who will potentially benefit from adjuvant chemotherapy, early treatment of micrometastatic disease, reduction in drug resistance by early exposure to treatment and downstaging with improved resectability. Potential disadvantages include: delay in local therapy secondary to toxicity, risk progression in chemoresistant patients and pre- operative complications. Several newly available chemotherapeutic agents are both highly active against NSCLC and potent radiosensitizers. The results of stage IIIA with induction treatment of clinical practice outside the clinical trial show a median survival of 22 months and a 3-year survival rate of 34% (10). An EORTC study (11) with carboplatin and paclitaxel used as induction regimen in patients with biopsy-proven stage N2 non-small cell lung cancer of the 52 eligible patients, 33 patients responded, one CR and 32 PR, for an overall response rate of 64% (95% CI, 48%- 76%). In addition, there were 10 patients with no changes (10%) and 9 with progressive disease (17%). The median duration of survival was 20.5 months (95% CI, 16.1-31.2 months) with an estimated 1-year survival rate of 68.5% (95% CI, 55.2-81.7). Furthermore, phase II neoadjuvant studies of docetaxel alone, in combination with cisplatin or carboplatin, or in combination with platinum and gemcitabine have produced promising results, with more recently reported RRs ranging from 44 to 82% and rates of complete resection raging from 67 to 79% (12) Complete surgical resection (13,14), tumor downstaging and pathologic complete response are predictors of long-term survival following neoadjuvant therapy. Pathologic complete response after induction chemotherapy generally ranges from 0% to 9.5%. Others higher complete response: one Martini (15) with 16.7% and one Kumar with 15% (16) are rare. Andre analyzed a cohort of 702 patients with resected N2 disease and identified four negative factors: preoperative clinical N2 status, involvement of multiple lymph node levels, pathological T3 or T4 disease, and absence of preoperative chemotherapy (17). Choi et al (18), reviewed cases of pathologic proven N2 disease, complete resection rate was 83,2% and overall 5-year was 23,3%. Five-year recurrence – free survival was 19,6%. Among 19 clinicopathological prognostic factors, incomplete resection and non- BACKGROUND NEOADJUVANT TREATMENTS PROGNOSTIC FACTORS AFTER NEOADJUVANT THERAPY