Christopher G. Wang

Incomplete Intrapulmonary Lymph Node Retrieval After Routine Pathologic Examination of Resected Lung Cancer

PURPOSE Pathologic nodal stage affects prognosis in patients with surgically resected non-small-cell lung cancer (NSCLC). Unlike examination of mediastinal lymph nodes (LNs), which depends on surgical practice, accurate examination of intrapulmonary (N1) nodes depends primarily on pathology practice. We investigated the completeness of N1 LN examination in NSCLC resection specimens and its potential impact on stage. PATIENTS AND METHODS We performed a case-control study of a special pathologic examination (SPE) protocol using thin gross dissection with retrieval and microscopic examination of all LN-like material on remnant NSCLC resection specimens after routine pathologic examination (RPE). We compared LNs retrieved by the SPE protocol with nodes examined after RPE of the same lung specimens and with those of an external control cohort. RESULTS We retrieved additional LNs in 66 (90%) of 73 patient cases and discovered metastasis in 56 (11%) of 514 retrieved LNs from 27% of all patients. We found unexpected LN metastasis in six (12%) of 50 node-negative patients. Three other patients had undetected satellite metastatic nodules. Pathologic stage was upgraded in eight (11%) of 73 patients. The time required for the SPE protocol decreased significantly with experience, with no change in the number of LNs found. CONCLUSION Standard pathology practice frequently leaves large numbers of N1 LNs unexamined, a clinically significant proportion of which harbor metastasis. By improving N1 LN examination, SPE can have an impact on prognosis and adjuvant management. We suggest adoption of the SPE to improve pathologic staging of resected NSCLC.

Cytotoxic chemotherapy in the contemporary management of metastatic castration‐resistant prostate cancer (mCRPC)

For several years, docetaxel was the only treatment shown to improve survival of patients with metastatic castration‐resistant prostate cancer (mCRPC). There are now several novel agents available, although chemotherapy with docetaxel and cabazitaxel continues to play an important role. However, the increasing number of available agents will inevitably affect the timing of chemotherapy and therefore it may be important to offer this approach before declining performance status renders patients ineligible for chemotherapy. Patient selection is also important to optimise treatment benefit. The role of predictive biomarkers has assumed greater importance due to the development of multiple agents and resistance to available agents. In addition, the optimal sequence of treatments remains undefined and requires further study in order to maximize long‐term outcomes. We provide an overview of the clinical data supporting the role of chemotherapy in the treatment of mCRPC and the emerging role in metastatic castration‐sensitive prostate cancer. We review the key issues in the management of patients including selection of patients for chemotherapy, when to start chemotherapy, and how best to sequence treatments to maximise outcomes. In addition, we briefly summarise the promising new chemotherapeutic agents in development in the context of emerging therapies.

Response to editorial titled 'Intrapulmonary lymph node retrieval: unclear benefit for aggressive pathologic dissection'.

The TNM staging system is currently our best prognostic tool in lung cancer, but poor application of this tool is an increasingly recognized worldwide problem in thoracic oncology (1-3). The main deficiency appears to be suboptimal pathologic lymph node staging, an important problem because lymph node metastasis is the gravest prognostic feature in patients without distant metastasis, who are candidates for curative surgical intervention. The statistics are startling: 17% of lung cancer resections in the US have no lymph nodes examined (pNX) (4), 40-50% of all resections (67% of resections with ‘pN0/pN1’ disease) have no mediastinal lymph nodes examined (5,6), 12% of patients have no hilar/intrapulmonary (N1) lymph nodes examined (7), the median total lymph node count is only 4-5 and less than 15% of patients have more than 10 lymph nodes examined (8-10).

Number and location of examined lymph nodes (LN) and survival after resection of node negative non-small cell lung cancer (NSCLC).

e17516 Background: LN metastasis profoundly affects prognosis of patients with resectable NSCLC. Variation in LN examination practice may impact staging accuracy. Evidence from other cancers suggests that patients with fewer examined LN have worse outcome. There is no established threshold number of LN to accurately determine node negativity in NSCLC. The AJCC 7 staging system suggests examination of at least 6 LN, others have suggested 11 to 16. Furthermore, we previously found inferior survival in N1 disease patients without mediastinal LN examination. We examined the impact of varying levels of LN examination in a surgical resection cohort. METHODS Review of all resections for NSCLC in Memphis, TN from 1/1/04 - 12/31/09. Preoperatively treated, pNx, LN-positive, margin positive patients were excluded. Patients were grouped according to AJCC 7 T-stage and sorted by number of examined LN and also by the presence of mediastinal LN in the pathology specimen. Survival was estimated by the Kaplan-Meier method and survival curves were compared by the log-rank test. RESULTS Majority of resections did not meet the AJCC LN minimum, fewer achieved the 11 lymph node standard (Table). T1 resections with <4 LN had inferior survival (p<0.04). There was a trend towards improvement with examination of greater than 6 and 10 lymph nodes (p>0.05 for all analyses). About 30% of patients of all T-stages had no mediastinal LN examined (Table 1). Patients with T2 and no mediastinal LN examination had significantly worse 5-year survival than those who had mediastinal LN examination (p<0.04). CONCLUSIONS We found no clear association between number of examined LN and survival in this LN-negative resection cohort. The low number of resections attaining high numbers of examined LN may have limited our dataset. In patients with T2N0 disease, resection without mediastinal LN examination significantly impairs survival. [Table: see text].