Missed Intrapulmonary Lymph Node Metastasis and Survival After Resection of Non-Small Cell Lung Cancer.

BACKGROUND: Pathologic nodal stage is a key prognostic factor for patients with surgically resected lung cancer. We previously described the extent of missed intrapulmonary nodal metastasis in a cohort of patients treated at institutions in metropolitan Memphis, TN. With long-term follow-up, we now quantify the survival impact of missed nodal metastasis. METHODS: We conducted a prospective cohort study to evaluate inadvertently discarded lymph nodes in re-dissected remnant lung resection specimens from lung cancer patients. Retrieved material was histologically examined and classified as lymph nodes with and without metastasis. Survival information was obtained from hospital cancer registries. We plotted survival distributions with the use of the Kaplan-Meier method and evaluated them with proportional hazards models that controlled for important demographic and clinical factors. RESULTS: The study included 110 patients who were 54% women and 69% white. Discarded lymph nodes with metastasis were found in 25 patients (23%). Patients with missed lymph node metastasis had an increased risk of death with an unadjusted hazard ratio of 2.0 (p = 0.06) and an adjusted hazard ratio of 1.4 (p = 0.45) compared with patients without missed lymph node metastasis. Patients with more than 2 missed lymph nodes with metastasis had 4.8 times the hazard of death (p = 0.0005) compared with patients without missed lymph node metastasis (adjusted hazard ratio 6.5, p = 0.0001). CONCLUSIONS: Metastasis to inadvertently discarded intrapulmonary lymph nodes from lung cancer resection specimens was associated with reduced survival. A more rigorous gross dissection protocol for lung cancer resection specimens may provide prognostically useful information.

Corticosteroids in the management of prostate cancer: a critical review.

Corticosteroids have been used in the management of prostate cancer for over 30 years. Although daily oral corticosteroids have frequently used in conjunction with chemotherapy for metastatic castration-resistant prostate cancer, their independent impact on survival is unclear. However, corticosteroids confer palliative benefits and are associated with objective responses and circulating tumor cell (CTC) and PSA declines in a small minority of patients, although toxicities such as osteoporosis and immunosuppression complicate long-term use. Following the demonstration of a palliative benefit for mitoxantrone combined with corticosteroids compared with corticosteroids alone, subsequent trials that demonstrated a benefit for first-line docetaxel over mitoxantrone, and second-line cabazitaxel over mitoxantrone, administered concurrent daily oral corticosteroids with all of these agents to maintain uniformity. Conversely, improved outcomes were demonstrated with docetaxel without corticosteroids for metastatic castration-sensitive prostate cancer. Daily oral corticosteroids are routinely combined with abiraterone to mitigate symptoms of mineralocorticoid excess. In contrast daily corticosteroids are not essential when administering enzalutamide or radium-223, and there is a concern of deleterious immune effects concurrently with sipuleucel-T. Given emerging evidence for promotion of resistance mechanisms, routine administration of daily oral corticosteroids in settings other than abiraterone administration and palliation of symptoms is probably not required.

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.

Size and histologic characteristics of lymph node material retrieved from tissue discarded after routine pathologic examination of lung cancer resection specimens.

Redissection of discarded lung resection specimens after routine pathology examination reveals missed lymph node metastasis. We sought to determine if size can be used to grossly select lymph nodes for microscopic examination. This is a prospective cohort study of lymph nodes retrieved from discarded lung resection specimens. The association between size and histologic characteristics of retrieved material was compared by the Wilcoxon-Mann-Whitney test. We retrieved 1094 grossly 'lymph node-like" tissue from 112 remnant lung resection specimens, of which 345 (32%) proved not to be lymph nodes and 71 (9%) of 749 lymph nodes had metastasis. Metastasis was present in discarded nodes in 26 (23%) of 112 patients. The non-lymph node tissue was significantly smaller than lymph nodes (P < .0001); lymph nodes with metastases were significantly larger than those without metastases (P < .0001). However, there was significant size overlap between the 3 types of grossly lymph node-like tissue. Thirty-two percent of nodes with metastasis were less than 1 cm; 15% of patients had at least 1 lymph node less than 1 cm with metastasis. The size difference between lymph nodes with and without metastasis is clinically unhelpful because of broad overlap. Size is insufficiently discriminatory and cannot be relied on to select materials for histologic examination. A third of grossly retrieved material was non-lymph node tissue. This probably occurs during routine pathologic examination and likely contributes to the low N1 lymph node count.

Dual intervention to improve pathologic staging of resectable lung cancer.

BACKGROUND: Detection of lymph node metastasis is of immense prognostic value in patients with resectable non-small cell lung cancer (NSCLC), but routine pathologic nodal staging is suboptimal. To determine the impact on the rate of detection of nodal metastasis, we tested dual intervention with a prelabeled lymph node specimen collection kit to improve intraoperative node dissection and a fastidious gross dissection of the lung resection specimen for intrapulmonary lymph nodes. METHODS: We matched dual-intervention cases with controls staged using standard surgical specimen collection and pathologic examination protocols. Controls were hierarchically matched for extent of resection, laterality, surgeon, pathologist, and T stage. All statistical comparisons were made with exact conditional logistic regression, to account for the matched case-control design. RESULTS: One hundred dual-intervention cases were matched with 100 controls. The dual interventions resulted in approximately a 3-fold increase in the number of lymph nodes examined and the number of lymph nodes with metastasis detected; they also increased the proportion of patients with lymph node metastasis from 21% to 35% (p = 0.02). There were strong trends toward higher aggregate stage distribution, and eligibility for postoperative adjuvant chemotherapy in the dual-intervention cases. CONCLUSIONS: The combination of interventions improved the thoroughness and accuracy of pathologic nodal staging. A prospective randomized trial to test the survival impact of the dual interventions is warranted.

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.

Use of a surgical specimen-collection kit to improve mediastinal lymph-node examination of resectable lung cancer.

INTRODUCTION: Pathologic examination of mediastinal lymph nodes (MLNs) after resection of non-small-cell lung cancer is critical in the determination of prognosis and postoperative management. Although systematic nodal dissection is recommended, the quality of pathologic lymph-node staging often falls short of recommendations in practice. We tested the feasibility of improving pathologic lymph-node staging of resectable non-small-cell lung cancer by using a prelabeled specimen-collection kit. METHODS: Case-control study with comparison of 51 resections, using a special lymph-node collection kit, with 51 controls matched for surgeon, extent of resection, pathologist, and T category. Appropriate statistical methods were used for all comparisons. RESULTS: The median number of MLNs examined increased from one in the control group, to six in the case group (p < 0.001). The percentage of resections attaining the National Comprehensive Cancer Network-recommended quality of MLN examination, and the proportion that would have been eligible for recent landmark postresection adjuvant therapy trials increased significantly (p < 0.001). The duration of surgery and postoperative complication rates were similar between cases and controls. Eighteen percent of kit cases had positive MLN, compared with 8% of controls. CONCLUSIONS: The use of a specialized specimen-collection kit for MLN examination was feasible, markedly improved MLN staging, and showed a trend toward increased detection of patients with MLN metastasis, with only a modest increase in duration of surgery, and no increase in perioperative morbidity, mortality, or hospital length of stay.