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Results for “Neoadjuvant therapy”

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PubMed1996

Optimal duration of neoadjuvant androgen withdrawal therapy before radical prostatectomy in clinically confined prostate cancer.

Experimental studies have shown that neoadjuvant androgen therapy dramatically reduces the rate of local recurrence after tumor excision. In the clinical setting, a 3-month course of neoadjuvant therapy before radical prostatectomy has been shown to significantly reduce positive margin rates, but follow-up is too short to assess the impact of such therapy on biochemical and clinical recurrence rates. A phase II study using an ultrasensitive assay showed that 8 months of neoadjuvant therapy were required before prostate-specific antigen (PSA) levels to reach their nadir in 84% of study participants. The positive margin rate in this study was substantially lower than those reported in the literature. Importantly, restaging of specimens after prostatic acid phosphatase (PAP) immunostaining did not upstage or increase positive margin rates. In addition, prolonged neoadjuvant therapy did not appear to result in progression of androgen-independent clones. A randomized phase III trial has been initiated to determine whether an 8-month course of neoadjuvant hormonal therapy is superior to a 3-month course in reducing positive margin rates and biochemical recurrences in patients with clinically confined prostate cancer.

Adult↗

PubMed2000

[Predictive factors of locally advanced disease in patients with prostatic cancer treated with neoadjuvant hormone therapy and radical prostatectomy].

AIM: To analyze the predictors of local adverse pathological findings (positive surgical margins and seminal involvement) in prostate cancer patients treated with neoadjuvant hormonotherapy and radical prostatectomy. PATIENTS AND METHODS: We studied seventy-eight patients treated with neoadjuvant androgen blockade prior to radical prostatectomy between 1995 and 1998. Age, PSA, prostate volume determined by transrectal ultrasound and/or magnetic resonance imaging, clinical stage, Gleason score, duration of blockade, pathological stage and tumoral volume were analyzed. RESULTS: 34.6% of patients (27/78) had adverse pathology (odds: 0.53). No significant differences were found in age, PSA, prostate volume, duration of blockade and Gleason score between organ-confined and locally advanced patients. Differences were found in tumor volume (p = 0.0001) but this was not different in order to positive or negative digital rectal examination (p = 0.5334). The efficacy for predicting pathological adverse findings was represented by ROC curves (PSA: 0.628, clinical stage: 0.612 and Gleason score: 0.545). Predictive table of extracapsular disease for different PSA levels, clinical stage and Gleason score were developed. No variable predicted positive margins in logistic regression model. CONCLUSIONS: Clinical variables do not predict locally advanced disease in prostate cancer patients treated with neoadjuvant androgen blockade. This is associated with higher tumor volumes. The probability of positive margins or seminal involvement increases with PSA level and Gleason score.

Aged↗

PubMed2002

Initial decline in hemoglobin during neoadjuvant hormonal therapy predicts for early prostate specific antigen failure following radiation and hormonal therapy for patients with intermediate and high-risk prostate cancer.

BACKGROUND: Declines in serum hemoglobin (Hgb) levels occur from the use of androgen suppression therapy (AST) in the treatment of prostate cancer patients. We studied whether time to prostate specific antigen (PSA) failure following external beam radiation therapy (RT) and AST could be predicted by the rate of decline in the Hgb level following the administration of neoadjuvant AST or by the Hgb level at presentation or at the start of RT. METHODS: The study cohort comprised 110 intermediate or high-risk prostate cancer patients who were managed using three-dimensional conformal RT (70 Gy) and 6 months of AST (2 months neoadjuvant, concurrent, and adjuvant). A Cox regression multivariable analysis was performed to evaluate the ability of the rate of decline of the Hgb from baseline to the start of RT, baseline PSA level, Gleason score, percent positive biopsies, and T-category to predict time to PSA failure. RESULTS: A decline in the Hgb level of 1 g/dL or more during the first month of AST was the only significant predictor of time to PSA failure (P = 0.02) on multivariable analysis. The relative risk of PSA failure (95% confidence interval) for patients with a decline in Hgb level during the first month (> or = 1 g/dL vs. < 1 g/dL) was 6.3 (2.4, 8.3) and the 3-year estimate of PSA outcome was 66% versus 82% (P = 0.04), respectively. There were no imbalances in the pretreatment prognostic factors or length of follow-up in each of these groups. CONCLUSION: A decline of 1 g/dL or more in Hgb level during the first month of neoadjuvant AST was a predictor of early PSA failure following RT and AST in intermediate and high-risk prostate cancer patients.

Aged↗

PubMed1997

Neoadjuvant androgen withdrawal therapy decreases local recurrence rates following tumor excision in the Shionogi tumor model.

PURPOSE: The role of neoadjuvant androgen withdrawal before radical prostatectomy continues to be defined and remains investigational. It is unknown whether decreases in positive margin rates will translate into lower biochemical and local recurrence rates until long-term followup is available. We determined whether local recurrence rates after tumor excision were less with neoadjuvant compared to adjuvant androgen ablation in the Shionogi tumor model. Androgen withdrawal in this model triggers apoptosis and complete tumor regression but rapidly growing androgen independent tumors inevitably recur after 1 month. Conceptually, the ideal time for excision is after maximal castration induced tumor involution but before outgrowth of androgen resistant clones. MATERIALS AND METHODS: Shionogi tumors were allowed to grow to 1 to 2 gm. before mice were randomly assigned to group 1-tumor excision with wide margins and castration at tumor recurrence and group 2-neoadjuvant castration for 10 days followed by wide excision of the regressed tumor. RESULTS: Tumors recurred locally in 87% of group 1 mice after a median of 17 days (range 6 to 24) and all regressed completely with adjuvant castration. However, androgen independent tumors recurred in 92% of mice after a median of 36 days. In group 2 androgen independent disease recurred in 44% of mice after a median of 40 days. Tumor-free survival was significantly greater in group 2 than in group 1 (56 versus 20%, respectively, p <0.05). Inked surgical resection margins were positive in two-thirds of group 1 and one-third of group 2 mice. CONCLUSIONS: Neoadjuvant androgen withdrawal decreases local recurrence and positive margin rates by 50% after tumor excision in the Shionogi tumor model. Although this model cannot address the issue of effect of neoadjuvant therapy on subclinical metastases, extrapolation of these results to the clinical disease suggests that neoadjuvant therapy may help to decrease not only the positive margin rates but also the subsequent risk of local recurrence following radical prostatectomy.

Animals↗

PubMed1993

Hormone ablation therapy as neoadjuvant treatment to radical prostatectomy.

Two hundred consecutive patients with presumed localized prostate cancer had radical prostatectomy alone (n = 119) or were treated for an average period of 3 months with combination therapy using the antiandrogen flutamide and one luteinizing hormone-releasing hormone (LHRH) agonist (Lupron or Zoladex). The positive margins decreased from 35.3% in the group undergoing prostatectomy alone to 11.5% in the group of men who received combination therapy before radical prostatectomy. In 41 apical tumors, the incidence of positive margins decreased from 50% in the control group to 18.6% in the combination therapy group. In stage C disease, the incidence of positive tumor showed a tendency to decrease with the extended duration of endocrine treatment with a rate of 37.5% after 3 months and 16.7% after 6 months. Whether the decreased incidence of positive surgical margins will all translate into prolonged survival remains to be verified by long-term follow-up of these patients. However, the initial results obtained in the present study are very encouraging.

Aged↗

PubMedDate not supplied

[Rectal cancer: locoregional recurrence in relation to surgical and complementary treatment].

Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant therapy. On the other hand, improvements in surgical techniques, as the total mesorectal excision, have apparently reduced the risk of LR. Furthermore, in selected cases, neoadjuvant therapy seems to reduce much more the incidence of LR. A list of prognostic factors which affect the onset of LR, other than the different procedures, was considered. To investigate such evidences a retrospective analysis was undertaken in our series, focusing on examination of the employed techniques as potential predictors of local recurrence. Thus, in a 18-yr-period (1986-2003), two hundred and ninety-five patients who had undergone elective curative surgical resection of rectal cancer were included in the study. The demographic, operative and follow-up data were collected retrospectively. All patients underwent total mesorectal excision, whereas neoadjuvant therapy was performed in a selected series of patients, according to defined entry criteria patterns. Results evidenced LR in 7.1% of patients and occurred between 6 months to 8 year following surgery. Comparisons were made between patients who had different surgical procedures; indeed sphyncter saving procedures correlated with a higher incidence of LR rather than abdomino-perineal resection. Pelvic recurrences were observed more frequently compared to the anastomotic ones. A limited number of patients with LR underwent surgery due to the associated condition of metastatic lesions; the follow-up related to such series evidenced a mortality rate of 57% within 3 year from reoperation. A low local recurrence rate can be achieved after total mesorectal excision (TME) without preoperative radiotherapy. Our results suggest that preoperative radiotherapy may be employed only for those patients who are at a higher risk for local recurrence.

Combined Modality Therapy↗

PubMed2002

[Adjuvant and neoadjuvant radiochemotherapy of rectal carcinoma].

Adequate surgical treatment is a prerequisite for any adjuvant and neoadjuvant therapy of rectal cancer. Randomized studies have investigated the role of radiotherapy for more than 20 years. At least two conclusions can be drawn from the data available by now: 1. Radiotherapy combined with 5-FU-chemotherapy is more effective than radiotherapy alone in the adjuvant setting. This prompted a National Cancer Institute Consensus Conference in the USA in 1990 and a German Cancer Society Consensus Conference in 1999 to recommend postoperative combined radiochemotherapy for patients with UICC-stage II and III rectal cancer as standard treatment outside clinical trials. 2. Preoperative radiotherapy is highly effective and can result in marked tumor shrinkage. In T4-tumors primarily not amenable to radical surgery (R0) and in locoregional recurrent disease preoperative radiotherapy in conventional fractionation with concurrent chemotherapy is standard of care in many institutions. Intensive, short-course preoperative radiotherapy according to the swedish concept (5 x 5 Gy) is now used frequently in patients with resectable rectal cancer due to short overall treatment time and early operation. However, major radio- and tumor biological shortcomings have also prompted criticism. Current studies investigate the role of preoperative short-course radiotherapy when surgery is optimized by total mesorectal excision and the role of combined preoperative as compared to postoperative radiochemotherapy for resectable stage II and III rectal cancer.

Chemotherapy, Adjuvant↗

PubMed1995

Neoadjuvant hormonal therapy before radical prostatectomy decreases the number of positive surgical margins in stage T2 prostate cancer: interim results of a prospective randomized trial. The Belgian Uro-Oncological Study Group.

PURPOSE: We investigated the effect of neoadjuvant treatment before radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 130 patients with stages T2b and T3 prostate cancer was randomized in a multicenter study: 62 underwent immediate radical prostatectomy and 65 received 560 mg. estramustine phosphate daily for 6 weeks preoperatively. RESULTS: For clinical stage T2b tumors the neoadjuvant treatment resulted in a significant decrease in positive surgical margins compared to the nonpretreated group. This difference was not found for clinical stage T3 tumors. The impact on progression and survival still must be analyzed. CONCLUSIONS: Neoadjuvant treatment can be beneficial for clinical stage T2 prostate cancer. Optimal treatment for stage T3 tumors remains controversial.

Aged↗

PubMed2026

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction ≥0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD↗

PubMed1996

Androgen receptor modulation in benign human prostatic tissue and prostatic adenocarcinoma during neoadjuvant endocrine combination therapy.

Modulation of androgen receptor (AR) expression during neoadjuvant endocrine therapy in human prostates of patients with localized prostate cancer was investigated by immunohistochemistry. In 8 of 15 untreated prostatectomy specimens, the majority of prostatic glandular cells displayed nuclear immunostaining for AR, whereas only 1 of 26 pretreated cases displayed a similar glandular AR expression. Expression of AR in the prostatic stromal compartment of nontreated cases proved to be quite heterogeneous, since 4 of the 15 (27%) examined specimens did not show stromal AR expression. After preoperative neoadjuvant therapy, this value was 68%, although this difference did not reach statistical significance. Prostatectomy specimens of the treated patients contained carcinomas with a higher Gleason score than those of untreated patients. AR expression in carcinomas of treated patients was diminished (P= 0.05), which may be attributed to their relatively lower differentiation grade. The data strongly suggest that neoadjuvant hormone therapy reduces AR expression by nonneoplastic prostatic glandular cells and carcinoma cells by a selective, but incomplete, elimination of AR-positive cells.

Adenocarcinoma↗

PubMed1997

[Neoadjuvant combined therapy in stage IIIA if non-small-cell bronchial cancer].

BACKGROUND AND OBJECTIVE: The overall prognosis of patients with stage IIIA non-small-cell lung cancer is unfavourable (median survival time 12 months). Tolerance to and efficacity of a multimodal neoadjuvant treatment was assessed in a prospective study. PATIENTS AND METHODS: 25 patients (median age 59 [37-69] years), with histologically confirmed mediastinal lymph node metastases, underwent chemotherapy. Immediately after two cycles with carboplatin/Ifosfamid (dimethoate)/etoposide they received hyperfractionated accelerated radiotherapy (45 Gy; 2 x 1.5 Gy daily) with simultaneous administration of carboplatin and vindesine. This was followed by tumour resection. RESULTS: After conclusion of the neoadjuvant treatment 19 of 25 patients (76%) had a remission. Of the 20 operated patients complete resection (R0) was possible in 17 (85%) and 14 of the 20 patients with resection (70%) had histologically demonstrated marked tumour regression. Critical toxicity consisted of pneumonitis and bronchial stump problems. Median survival time of all patients was 24.8 months and for patients with R0 resection 35.9 months. CONCLUSION: Neoadjuvant multimodal treatment of stage IIIA non-small-cell lung cancer can achieve prolongation in survival time. The place of radiotherapy or radiotherapy with chemotherapy in such a treatment concept will need to be defined in a randomized study.

Adult↗

PubMed2005

The role of luteinizing hormone-releasing hormone therapy in locally advanced prostate cancer and biochemical failure: considerations for optimal use.

BACKGROUND: More patients are being diagnosed with prostate cancer at an earlier age with earlier stage disease because of advances in screening and detection. Investigators continue to explore the use of hormone therapy, particularly luteinizing hormone-releasing hormone (LHRH) analogues, earlier in the course of disease. OBJECTIVE: This review summarizes clinical evidence regarding the safety and efficacy of LHRH analogues in the treatment of locoregional disease or following biochemical failure. METHODS: Relevant information from clinical studies was identified through a MEDLINE search of the medical literature published in English in the last 5 years (search terms: LHRH and prostate cancer). The search included prospective and retrospective clinical studies on LHRH therapy in locally advanced prostate cancer. Additional relevant publications published before 1999 were identified from citations in the resulting articles. RESULTS: The available clinical evidence suggests that the use of LHRH analogues as adjuvant or neoadjuvant therapy in conjunction with radiation therapy may improve survival outcomes. Few studies have evaluated the use of LHRH analogues after biochemical failure. However, several related studies indicate that initiating hormone therapy earlier rather than later may provide some clinical benefit. When considering early initiation of LHRH therapy, the potential risks of long-term treatment must be considered. Physiologic changes, such as deterioration of body composition and bone quality, may have important effects on the risk of developing cardiovascular disease and osteoporosis. CONCLUSIONS: Although some clinical evidence supports the use of LHRH analogues as adjuvant or neoadjuvant therapy or following biochemical failure, further study is needed. In the meantime, clinicians should carefully weigh the potential benefits and risks of early hormone therapy when making treatment decisions.

Chemotherapy, Adjuvant↗

PubMed2003

Mature survival results with preoperative cisplatin, protracted infusion 5-fluorouracil, and 44-Gy radiotherapy for esophageal cancer.

PURPOSE: To assess the long-term survival results after cisplatin, protracted infusion 5-fluorouracil, and concurrent radiotherapy (RT) followed by surgical resection of esophageal cancer. METHODS AND MATERIALS: Ninety-two patients with esophageal cancer (65 with adenocarcinoma and 27 with squamous cell carcinoma) were treated in two sequential protocols of preoperative chemoradiotherapy. The patients had tumor confined to the esophagus and regional nodes, including celiac nodes for middle and distal lesions. In trial A (1989-1994), 50 patients were treated with 44 Gy RT (2 Gy/d) along with concurrent 5-fluorouracil 300 mg/m(2)/d given by protracted venous infusion on Days 1-30 and cisplatin 26 mg/m(2) on Days 1-5 and 26-30. In trial B (1995-1997, 42 patients), the chemotherapy dosages during RT were reduced to 5-fluorouracil 225 mg/m(2)/d protracted venous infusion and cisplatin 20 mg/m(2)/d on Days 1-5 and 16-30; three cycles of paclitaxel 135 mg/m(2)and cisplatin 75 mg/m(2) were given postoperatively. Surgery generally occurred 4-6 weeks after completion of the planned preoperative therapy. Transhiatal resection was performed whenever possible. RESULTS: Of the 92 patients, 86 (93%) underwent surgery (1 refused, 2 died preoperatively, and 3 developed evidence of metastatic disease). Of the 92 patients, 80 (87%) had complete resections with negative margins (3 had positive margins and 3 had distant metastases discovered at surgery). The pathologic complete response rate was 33% (30 of 92). The median follow-up was 63.5 months. The median survival and disease-specific survival for all enrolled patients was 35 and 59 months, respectively. The 5-year survival and disease-specific survival rate was 40% and 49%, respectively. Patients with a pathologic complete response had a 67% survival rate at 5 years (median not reached), and the remainder of patients had a 5-year survival rate of 27% (median 21 months; p <0.001). For 21 patients alive after 5 years (60-121 months), 2 died of their disease and all others were disease free. Eight patients with pathologic Stage I tumor at the time of surgery had survival similar to those with a complete response to preoperative therapy. The median survival for patients with pathologic Stage IIA, IIB, III, and IV disease at the time of surgery was 22, 13.5, 18, and 4.9 months, respectively. The pattern of initial failure was local/regional alone in 6% (5 of 90), local/regional plus distant in 3% (3 of 90), and distant alone in 47% (42 of 90). No differences were noted in survival or response rate between those with adenocarcinoma or squamous cell carcinoma. CONCLUSION: The promising 5-year survival results and low rate of late cancer-related deaths suggest that these regimens of intensive neoadjuvant therapy may improve the overall cure rate. The pathologic stage after neoadjuvant therapy is an important predictor of survival and may be useful in selecting patients for novel adjuvant therapies. Isolated local failure is uncommon, indicating that efforts to improve the therapeutic outcome should focus on optimizing systemic therapy rather than intensifying the RT. Additional randomized data are needed to assess the benefits of this therapeutic approach fully.

Adenocarcinoma↗

PubMedDate not supplied

Resection of stage III non-small cell lung cancer following induction therapy.

Approximately 25%-30% of all patients with non-small cell lung cancer (NSCLC) present with stage III tumors. Except for specific subsets, these tumors are not usually amenable to complete surgical resection and are associated with a 5-year survival of 10% or less. Because patients with stage III NSCLC die of distant metastases, recent efforts to improve the prognosis of these tumors have focused on neoadjuvant therapy using chemotherapy or chemoradiotherapy as induction treatment and subsequent surgical resection for local control. Many trial have now shown the feasibility of neoadjuvant therapy and suggest that overall survival is approximately double that seen after surgical resection or radiation alone. Future clinical trials will define whether surgical resection after induction therapy provides better local and control and survival than chemotherapy and high-dose radiation alone.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1995

[Surgical therapy of locally advanced non-small cell lung carcinoma].

Experience during the past 10 years has shown up different opinions on the surgical treatment of patients with stage III non-small cell lung cancer. In the light of high resectability and survival rates (respectively 80.8% and 40% at 2 years in the experience of the Southwest Oncology Group) produced with neoadjuvant therapy (followed by surgery) it appears to be an appealing therapeutic option. Until recently, there have been no large prospective randomized phase III trials to answer the question of whether neoadjuvant therapy is superior to other treatment modalities (surgical resection alone; non-surgical treatment).

Carcinoma, Non-Small-Cell Lung↗

PubMed2002

Prognoses of T4 breast cancer subsets.

BACKGROUND: The relative prognoses of subsets of patients with T4 breast tumors, since the advent of neoadjuvant therapy, are unknown, although inflammatory carcinoma (T4d) is considered to have the worst prognosis. METHODS: Subsets of T4 patients were analyzed for the incidence of distant metastases at presentation (M1; n = 263). T4M0 patients treated with neoadjuvant therapy (n = 126) were analyzed for relapse-free survival (RFS). T4d tumors with (Cut/CW+) and without (Cut/CW-) skin nodules, posterior fixation, or both were analyzed separately. RESULTS: Fewer patients with T4d (Cut/CW-) tumors had distant metastases at presentation than T4d (Cut/CW+) patients or T4b and T4c patients (P =.001,.001, and.009, respectively). RFS was longer for T4b patients than for T4c patients (P =.018) or T4d (Cut/CW+) patients (P =.003). RFS of the T4d (Cut/CW+) patients was shorter than for T4d (Cut/CW-) patients (P =.050). CONCLUSIONS: The incidence of distant metastases at presentation was lowest, and RFS was longest, for patients with T4d tumors not grossly involving the skin or posterior structures. Patients whose tumors grossly invaded both skin and posterior structures (T4c) or those with T4d tumors grossly invading either most frequently presented with distant metastases and had the shortest RFS.

Breast Neoplasms↗

PubMed1994

Neoadjuvant intra-arterial chemotherapy in locally advanced breast cancer: a prospective randomized study. Osaka Breast Cancer Study Group.

A prospective randomized study of neoadjuvant chemotherapy was carried out on 73 patients with locally advanced breast cancer. Group A (n 26) received no neoadjuvant therapy, group B (n22) received intra-arterial infusions of epirubicin and group C (n25) received intravenous epirubicin. The regression of the primary tumor was significantly higher in group B than in group C (68.2 vs 36.0%, P < 0.05). The post-operative survival of responders to neoadjuvant therapy was better than that of non-responders. Side effects were milder in group B than in group C. There was, however, no difference among the three groups in terms of overall and disease-free survivals. Thus, neoadjuvant intra-arterial chemotherapy was effective for achieving loco-regional control of locally advanced breast cancer with a low toxicity, but could not improve survival.

Aged↗

PubMed2005

Detection of disseminated tumor cells in mediastinoscopic lymph node biopsies and lymphadenectomy specimens of patients with NSCLC by quantitative RT-PCR.

OBJECTIVE: Detection of disseminated tumor cells in mediastinoscopic biopsies could improve staging and might be helpful concerning indications for neoadjuvant therapy regimens. This prospective study was performed to evaluate a simple and observer-independent polymerase chain reaction (PCR)-based method for the detection of disseminated tumor cells in regional lymph nodes. METHODS: Lymph nodes of 32 consecutive patients without neoadjuvant therapy were removed by systematic lymphadenectomy during resection of primary NSCLC. One hundred of these lymph nodes were cut into two equal halves which were examined using either routine histopathology or quantitative reverse transcriptase PCR (qRT-PCR). qRT-PCR amplification of cytokeratin 19 (CK19) transcripts was applied for the detection of tumor cell-specific RNA. We differentiated between illegitimate marker gene transcription and cancer-specific expression by using a cut-off value that was obtained from the analysis of 18 lymph nodes of patients with benign lung diseases. Subsequent to the evaluation of qRT-PCR, a pilot project with five additional patients was conducted to examine 19 mediastinoscopic biopsies, which were cut into two equal halves and proceeded as described above. RESULTS: Ninety-four (94%) lymph nodes were tumor-free by histopathology. qRT-PCR detected disseminated tumor cells in 26 (28%) of these lymph nodes. All of the remaining six lymph nodes that were judged by the pathologist to contain tumor cells exhibited CK19 transcripts. Twenty-three patients had a pN0 status. qRT-PCR detected disseminated tumor cells in 13 (56%) of these pN0 patients. The mediastinoscopic biopsies showed disseminated tumor cells in four (21%) out of 19 histopathologically tumor-free samples. CONCLUSIONS: CK19 qRT-PCR is a sensitive and specific tools for the detection of disseminated tumor cells in regional lymph nodes of patients with operable NSCLC. Further studies are required to asses if this molecular method might improve mediastinoscopic staging.

Aged↗