If we were discussing this case before he had the lung biopsy, we should analyze the differential diagnosis of pulmonary nodules on a prostate cancer patient (benign lesion, metastasis, or primary bronchogenic carcinoma). The presence of multiple lung nodules is much more common to metastasis. On the other hand, the likelihood that a solitary pulmonary nodule represents a primary bronchogenic carcinoma or a metastasis depends on the primary location of the extrapulmonary tumor. For cancers of the prostate, urinary bladder, breast, uterine cervix, ovary, common bile duct, esophagus, and stomach, a patient with a solitary pulmonary nodule is much more likely to have a primary bronchogenic carcinoma than a lung metastasis. Cancers of the colon, kidney, and uterus have a fairly even chance of demonstrating a primary lung cancer versus a metastasis. Patients with melanomas, bone tumors and soft tissue sarcomas, or testicular cancers are much more likely to have a solitary metastasis than a primary lung cancer (CAHAN; SHAH; CASTRO, 1978; QUINT; PARK; IANNETTONI, 2000). However, the patient did have lung biopsy that showed adenocarcinoma, confirming two different neoplasms. So, he has an aggressive and metastatic prostate cancer that should be treated with hormone therapy, and a potentially curable lung cancer for which local resection should be considered. Of course, there is no indication for radical local prostate cancer therapy (neither surgery, nor radiotherapy). The L4 lesion should be followed, and local radiotherapy may be necessary if he continues with back pain or develops signs of spinal cord compression.

Dear Dr Frederico Romero.

Thank you so much for the nice information.

This patient was referred to us after he already received radiotherapy to the L4 lesion. We discussed the case in the thoracic and genitourinary multidisciplinary clinics. Almost all of us believe that the metastatic cancer is the prostate given the high Gleason score, seminal vesicle invasion and the high PSA, in addition to the early (intra-thoracic stage) for the NSCLC; T1 N0. However, some of the members suggested that a biopsy of the L4 lesion is needed because in rare situations you can have an oligometastatic NSCLC with early intra-thoracic stage, and because management would change dramatically if that was the case.

I am not sure if a biopsy of the L4 lesion will help after he already received radiotherapy to that lesion. We will treat this patient with lobectomy (for the NSCLC), and with bilateral subcapsular orchidectomy.

Do you think that biopsy of the L4 lesion is indicated ?

I'd say that added information in a case may be proven futile, but rarely if ever is harmful. The L4 lesion has already received RT, and as another therapy choice may be orthopedic surgery on the vertebra, the surgical procedure would allow obtaining histologic material from the bone metastasis, if it comes from the LC, you may know if it has an EGFR mutation, pointing to an specific targeted therapy.

Bisphosphonate therapy may be considered in this patient, and there's a drug that has an approved indication in both Prostate Cancer and NSCLC -Docetaxel, ChemoTherapy can be envisaged that includes this drug, if you're to use a Pt compound, you know that the oral drug SatraPlatin showed some efficacy in Prostate Ca, thus, the use of a TP combination CT would probably improve this patient.

I attach a document on the use of AntiAndrogen therapy switch plus UFT in Prostate Ca, and as UFT has shown activity in NSCLC, it may be an option worth considering. Regading UFT, you know that it can be modulated by LV, that when using LV to modulate a FluoroPyrimidine, LV should be dosed at least 30-60 min before FP to allow its metabolization, and a bid UFT dosing was shown producing a better AUC than the originally proposed tid dosing schedule.

Please keep us aware of how the patient is doing. Thanks. Salut †

1. Int J Oncol. 2013 Sep;43(3):713-20. doi: 10.3892/ijo.2013.1997. Epub 2013 Jun 28.

Substitution of anti-androgens and tegafur-uracil combination therapy for

castration-resistant prostate cancer: Results of a multi-center randomized phase

II study.

Takahashi M, Kawabata R, Kawano A, Murakami Y, Sutou Y, Inai T, Akazawa S, Hamao

T, Hayashi H, Fukawa T, Takemura M, Yamamoto Y, Yamaguchi K, Izaki H, Fukumori T,

Kanayama H.

Department of Urology, Institute of Health Biosciences, The University of

Tokushima Graduate School, Tokushima 770-8503, Japan.

We conducted this study to determine whether substitution with anti-androgen

(SOA) and tegafur-uracil (a pro‑drug of 5-FU) combination therapy is more

effective than SOA alone after relapse from initial hormonal therapy. Patients

who were histologically confirmed and relapsed after initial hormonal therapy

were included. All patients were randomly allocated into two groups: SOA alone

(group A) or SOA combined with tegafur-uracil (group B). The mRNA expression of

four enzymes, including thymidylate synthase (TS), dihydropyrimidine

dehydrogenase (DPD), orotate phospho-ribosyltransferase (OPRT) and thymidine

phosphorylase (TP), in prostate cancer cells was analyzed by quantitative

reverse-transcription polymerase chain reaction. Fifty-two patients were enrolled

in this study. The median age was 77 (range: 47-92) years. The PSA response rate

in group B (61.5%) tended to be higher compared to that in group A (34.6%)

(p=0.095). Group B (median: 15.9 months) had a significantly longer time to PSA

progression (TTP) compared to group A (6.4 months) (p=0.014). In patients with a

lower TS expression or a higher OPRT expression, group B demonstrated a higher

PSA response rate compared to group A (p=0.019 and p=0.041, respectively). In

addition, in the patients with a lower TS expression, group B demonstrated a

significantly longer TTP compared to group A (p=0.018). There were no severe

adverse events in either treatment group. After relapse from initial hormonal

therapy, SOA combined with tegafur-uracil is effective and well tolerated. The TS

mRNA expression level may be a predictive factor for this combination therapy.

PMID: 23817692 [PubMed - in process]

Dear Jose,

As always, I am impressed with the data you present. Nevertheless, and from a clinical prospective, we assume that this patient has early stage NSCLC, and if this stage is confirmed following lobectomy and mediastinal LN dissection, and if LN turned to be negative, then there is no need for any adjuvant therapy for the NSCLC (that include Docetaxel), additionally, for his metastatic prostate cancer (which is the likely case), there is no need to start chemotherapy. We usually start with surgical or medical castration (through bilateral orchidectomy or an LHRH analogue). Some physicians may recommend adding an anti androgen (bicalutamide) as a combined androgen blockade strategy although the impact of this strategy on overall survival is unclear.

I agree with you that probably surgical resection and pathologic diagnosis of the vertebral metastases may be better than radiotherapy as it provides pathologic daignosis, and in the rare situation of oligometastatic NSCl, this may be associated with prolonged survival if the mediastinal LN following lobectomy are negative (Ref: Murakami H, Kawahara N, Demura S. Total en bloc spondylectomy for lung cancer metastasis to the spine. J Neurosurg Spine 2010;13(October (4)):

414–7) (ref: Salah S, et al. Metastatectomy for extra-cranial extra-adrenal non-small cell lung cancer solitary metastases: systematic review and analysis of reported cases. Lung Cancer. 2012 Jan;75(1):9-14. ) (Ref: Gomez DR, et al. Oligometastatic disease at presentation or recurrence for nonsmall cell lung cancer. Pulm Med. 2012;2012:396592).

Regarding the use of Tegafur-uracil in addition to anti-androgen, we do not have Tegafur in our country, and it is not a standard therapy for metastatic prostate cancer up to the best of my knowledge. Furthermore, most of the evidence about the benefit from Tegafur came from Japanese studies. Of course I am impressed with the Japanese studies, however; I am always concerned with the probability that there are racial differences. Remember for example that the Japanese showed in a randomized trial that combined androgen blockade with bicalutamide and LHRH analogue is associated with improvement time to progression, time to treatment failure, and OS compared to LHRH alone (Akaza H, et al. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol 2004; 34: 20–8). Unfortunately, this was not confirmed in other studies conducted on caucasian populations. For that reason, I will not recommend Tegafur, and would not extrapolate data from Japanese patients and apply it on our patients.

I agree with you about the surgery for the L4 lesion, this option should had been discussed before the patient was treated with radiotherapy, and even in the worst clinical scenario (if the metastatic cancer is the NSCLC, which is the less likely possibility), there is some evidence that surgery may improve the outcome and may be associated with long term survival, Please see the attached reference.

I will keep you updated about the patient.

I really appreciate all the comments. This is not an easy case to manage, and for that reason sharing opinions is really important.

http://www.ncbi.nlm.nih.gov/pubmed/20887137

Here's to you the publication of the Japanese trial of Adjuvant UFT in stage I NSCLC, pointing better results in AdenoCa, as there is some literature about the activity of UFT in Prostate Ca, you may point to two birds with the same shot

1. Ann Oncol. 2005 Jan;16(1):75-80.

A randomized phase III trial of adjuvant chemotherapy with UFT for completely

resected pathological stage I non-small-cell lung cancer: the West Japan Study

Group for Lung Cancer Surgery (WJSG)--the 4th study.

Nakagawa M, Tanaka F, Tsubota N, Ohta M, Takao M, Wada H; West Japan Study Group

for Lung Cancer Surgery.

Department of Thoracic Surgery, Kyoto University, Kyoto, Japan.

PURPOSE: To examine the efficacy of UFT, an oral 5-fluorouracil derivative agent,

as post-operative adjuvant therapy for pathologic (p-) stage I non-small-cell

lung cancer (NSCLC), because a previous randomized study had suggested it was

efficacious for early-stage NSCLC patients.

PATIENTS AND METHODS: Patients with completely resected p-stage I, adenocarcinoma

or squamous cell carcinoma were eligible. A total of 332 patients were randomized

to the surgery-alone group (control group) and the treatment group (UFT 400

mg/m(2) for 1 year after surgery, UFT group) after stratification by the

histologic types.

RESULTS: For all patients, the 5- and 8-year survival rates for the UFT group

were 82.2% and 73.0%, and those for the control group were 75.9% and 61.2%,

respectively; no statistically significant improvement of survival was achieved

by UFT administration (P=0.105). For Ad patients, the 5- and 8-year survival

rates of the UFT group (n=120) were 85.2% and 79.5%, respectively, which seemed

better than those of the control group (n=121) (79.2% and 64.0%, respectively;

P=0.081). For squamous cell carcinoma patients, there was also no difference in

survival between the control group (n=48) and the UFT group (n=43) (P=0.762). For

all pT1 patients, the 5- and 8-year survival rates of the UFT group were 83.6%

and 82.1%, respectively, significantly better than those of the control group

(77.9% and 57.6%, respectively, P=0.036); UFT was not significantly effective for

pT2 patients. For pT1 adenocarcinoma patients, UFT administration markedly

improved the survival (P=0.011).

CONCLUSION: Post-operative UFT administration did not significantly improve

post-operative survival of p-stage I NSCLC patients. Subset analyses suggested

that UFT might be effective in pT1N0M0 adenocarcinoma patients.

PMID: 15598942 [PubMed - indexed for MEDLINE]

1. J Surg Oncol. 2002 Oct;81(2):87-92.

Predictive value of dihydropyrimidine dehydrogenase expression in tumor tissue,

regarding the efficacy of postoperatively administered UFT (Tegafur + Uracil) in

patients with p-stage I nonsmall-cell lung cancer.

Nakagawa T, Tanaka F, Takata T, Matsuoka K, Miyahara R, Otake Y, Yanagihara K,

Fukushimab M, Wada H.

Department of Thoracic Surgery, Faculty of Medicine, Kyoto University, Sakyo-ku,

Kyoto, Japan.

BACKGROUND AND OBJECTIVES: Dihydropyrimidine dehydrogenase (DPD) activity in

tumor cells has been suggested to be one of the factors determining the

effectiveness of 5-fluorouracil (5-FU). In the present study, we analyzed DPD

expression in tumors and investigated retrospectively the relationship between

the efficacy of UFT (Tegafur + Uracil) as adjuvant chemotherapy and DPD

expression in nonsmall-cell lung cancer (NSCLC).

METHODS: DPD expression of 166 resected p-stage I NSCLC was examined

immunohistochemically. Patients who were administered UFT alone as adjuvant

therapy comprised the UFT group (n = 54), and those who underwent only surgery

comprised the control group (n = 112). DPD expression was categorized as either

high or low, according to intensity of staining.

RESULTS: DPD expression was high in 98 patients (59.0%) and low in 68 patients

(41.0%). Patients with low-DPD tumors who were administered UFT had a

significantly better prognosis than those who did not receive adjuvant treatment

(P = 0.021). No significant difference was found between the two groups of

patients with high-DPD tumors (P = 0.598).

CONCLUSIONS: DPD expression may predict the efficacy of UFT after surgery for

p-stage I NSCLC. A prospective study is needed to confirm the role of DPD

expression as a predictor of UFT efficacy.

Copyright 2002 Wiley-Liss, Inc.

PMID: 12355409 [PubMed - indexed for MEDLINE]

1. Br J Cancer. 2001 Jan;84(2):263-9.

Apoptosis and p53 status predict the efficacy of postoperative administration of

UFT in non-small cell lung cancer.

Tanaka F, Otake Y, Yanagihara K, Yamada T, Miyahara R, Kawano Y, Li M, Inui K,

Wada H.

Department of Thoracic Surgery, Faculty of Medicine, Kyoto University,

Shogoin-kawahara-cho 54, Sakyo-ku, Kyoto, 606-8397, Japan.

To examine whether efficacy of postoperative oral administration of UFT, a

5-fluorouracil derivative chemotherapeutic agent, may be influenced by incidence

of apoptosis (apoptosis index) or apoptosis-related gene status (p53 and bcl-2)

of the tumour, a total of 162 patients with pathologic stage I non-small cell

lung cancer were retrospectively reviewed. UFT was administrated postoperatively

to 44 patients (UFT group), and not to the other 118 patients (Control group).

For all patients, 5-year survival rate of the UFT group (79.9%) seemed higher

than that of the Control group (69.8%), although without significant difference

(P = 0.054). For patients with higher apoptotic index, 5-year survival rate of

the UFT group (83.3%) was significantly higher than that of the Control group

(67.6%, P = 0.039); for patients with lower apoptotic index, however, there was

no difference in the prognosis between these two groups. Similarly, UFT was

effective for patients without p53 aberrant expression (5-year survival rates:

95.2% for the UFT group and 74.3% for the Control group, P = 0.022), whereas not

effective for patients with p53 aberrant expression. Bcl-2 status did not

influence the efficacy of UFT. In conclusion, apoptotic index and p53 status are

useful factors to predict the efficacy of postoperative adjuvant therapy using

UFT.

Copyright 2001 Cancer Research Campaign.

PMCID: PMC2363717

PMID: 11161386 [PubMed - indexed for MEDLINE]

Int J Clin Oncol. 2005 Jun;10(3):157-64.

Postoperative adjuvant therapy for completely resected early-stage non-small cell

lung cancer.

Kato H, Tsuboi M, Kato Y, Ikeda N, Okunaka T, Hamada C.

Department of Surgery, Tokyo Medical University, 6-7-1 Nishi-shinjuku, Tokyo

160-0023, Japan.

Consensus on adjuvant therapy for completely resected non-small cell lung cancer

until 2002 was as follows. (1) There was no significant impact of postoperative

adjuvant chemotherapy based on meta-analysis and previous clinical trials. (2)

Confirmatory studies are necessary in large-scale prospective clinical trials.

However, recent mega trials have introduced epoch-making changes for

postoperative adjuvant chemotherapy in clinical practice since ASCO 2003. The

effectiveness of UFT in N0 patients was confirmed. Patients with completely

resected stage I non-small cell lung cancer, especially T2N0 adenocarcinoma, will

benefit from adjuvant chemotherapy with UFT. The results of the International

Adjuvant Lung Trial (IALT) have confirmed the meta-analysis in 1995. Also, both

the JBR10 and Cancer and Leukemia Group B (CALGB) 9633 studies have also

confirmed positive IALT results of the benefit for postoperative platinum-based

chemotherapy in completely resected non-small cell lung cancer. Adjuvant

chemotherapy for pathological stage IB to II, completely resected non-small cell

lung cancer is standard care based on clinical trials. UFT showed the strongest

evidence for IB in Japan. Platinum doublet chemotherapy with third-generation

anticancer agents is also recommended. Adjuvant chemotherapy should be offered as

standard care to patients after completely resected early stage non-small cell

lung cancer. However, there is no evidence of the feasibility and efficacy for

adjuvant chemotherapy with the platinum-based regimen in Japan. Careful

management should be necessary in such treatment.

PMID: 15990962 [PubMed - indexed for MEDLINE]

J Clin Oncol. 2005 Aug 1;23(22):4999-5006.

Meta-analysis of postoperative adjuvant chemotherapy with tegafur-uracil in

non-small-cell lung cancer.

Hamada C, Tanaka F, Ohta M, Fujimura S, Kodama K, Imaizumi M, Wada H.

Faculty of Engineering, Tokyo University of Science, Shinjuku-ku, Tokyo 162-8601,

Japan. [email protected]

PURPOSE: Recent clinical trials have shown the efficacy of platinum-based

adjuvant chemotherapy for completely resected non-small-cell lung cancer (NSCLC).

In Japan, many clinical trials of adjuvant chemotherapy with tegafur-uracil (UFT)

have been conducted, and some trials showed positive results while others showed

negative results. Thus, we performed a meta-analysis to assess the efficacy of

postoperative adjuvant chemotherapy with UFT in NSCLC.

METHODS: Among nine trials of postoperative adjuvant UFT-containing chemotherapy,

six trials comparing surgery alone with surgery plus UFT were identified. Of six

trials, two were three-arm trials including cisplatin-based chemotherapy followed

by UFT, and data from that arm were not included in the meta-analysis.

RESULTS: Of 2,003 eligible patients, most (98.8%) had squamous cell carcinoma or

adenocarcinoma, and most had stage I disease; the tumor classification was T1 in

1,308 (65.3%), T2 in 674 (33.6%), and the nodal status was N0 in 1,923 (96.0%).

The two treatment groups did not differ significantly in major prognostic

factors. The median duration of follow-up was 6.44 years. The survival rates at 5

and 7 years were significantly higher in the surgery plus UFT group (81.5% and

76.5%, respectively) than in the surgery alone group (77.2% and 69.5%,

respectively; P = .011 and .001, respectively). The overall pooled hazard ratio

was 0.74, and its 95% CI was 0.61 to 0.88 (P = .001).

CONCLUSION: This meta-analysis showed that postoperative adjuvant chemotherapy

with UFT was associated with improved 5- and 7-year survival in a Japanese

patient population composed primarily of stage I adenocarcinoma patients.

PMID: 16051951 [PubMed - indexed for MEDLINE]

J Thorac Oncol. 2009 Dec;4(12):1511-6. doi: 10.1097/JTO.0b013e3181bbf1f2.

Effect of postoperative adjuvant chemotherapy with tegafur-uracil on survival in

patients with stage IA non-small cell lung cancer: an exploratory analysis from a

meta-analysis of six randomized controlled trials.

Hamada C, Tsuboi M, Ohta M, Fujimura S, Kodama K, Imaizumi M, Wada H.

Faculty of Engineering, Tokyo University of Science, Tokyo, Japan.

[email protected]

BACKGROUND: The Seventh Edition of the Tumor, Node, Metastasis Classification of

Malignant Tumors in non-small cell lung cancer (NSCLC) proposes a more detailed

classification of primary tumor diameter. Stage IA T1 disease is subdivided into

two groups: T1a disease (tumor diameter, < or = 2 cm) and T1b disease (tumor

diameter, >2 to < or = 3 cm). Tegafur-uracil (UFT) improves survival in patients

with stage I NSCLC. However, whether it is effective in patients with T1 disease

(stage IA) remains controversial.

METHODS: Data from a 2005 meta-analysis of UFT were reanalyzed to evaluate the

effectiveness of UFT according to T1a and T1b tumors as proposed by the new

tumor, node, metastasis classification in patients who had T1 tumors with no

lymph-node metastasis.

RESULTS: Data from 1269 patients were analyzed: 670 (52.8%) had T1a tumors and

599 (47.2%) had T1b tumors. In the surgery-alone group, survival rates at 5 years

were 85% in patients with T1a tumors and 82% in those with T1b tumors after

surgery alone and 87% in patients with T1a tumors and 88% in those with T1b

tumors after surgery followed by adjuvant treatment with UFT. In patients with

T1b tumors, the survival rate was significantly higher in the UFT group than in

the surgery-alone group (hazard ratio = 0.62; 95% confidence interval, 0.42-0.90;

log-rank p = 0.011). The hazard ratio for death in the UFT group when compared

with the surgery-alone group was 0.84 for those with T1a disease (95% confidence

interval, 0.58-1.23). The results of a test for interaction between treatment

response and T1 subgroup were not significant (p = 0.30).

CONCLUSIONS: UFT significantly improves survival in patients with stage IA T1b

NSCLC compared with surgery alone.

PMID: 19875974 [PubMed - indexed for MEDLINE]

Anticancer Res. 2007 Jul-Aug;27(4C):2641-8.

Predictive value of thymidylate synthase and dihydropyrimidine dehydrogenase

expression in tumor tissue, regarding the efficacy of postoperatively

administered UFT (tegafur+uracil) in patients with non-small cell lung cancer.

Miyoshi T, Kondo K, Toba H, Yoshida M, Fujino H, Kenzaki K, Sakiyama S, Takehisa

M, Tangoku A.

Department of Oncological and Regenerative Surgery, Institute of Health

Bioscience, University of Tokushima Graduate School, Kuramoto-cho, Tokushima,

Japan.

BACKGROUND: UFT (tegafur + uracil) has been reported to be effective as an

adjuvant in postoperative chemotherapy for non-small cell lung cancer (NSCLC) in

a randomized prospective study. Thymidylate synthase (TS) and dihydropyrimidine

dehydrogenase (DPD) expression were investigated in resected tumors and the

relationship between their expression and clinical factors in NSCLC patients was

examined.

PATIENTS AND METHODS: Fifty-four NSCLC patients had undergone complete surgical

resection and lymph node dissection, and had been administered UFT post-surgery.

The TS and DPD expression in the tumor tissues was evaluated by

immunohistochemical staining. The relationship between TS and/or DPD expression

and clinicopathological factors was examined.

RESULTS: There were 38 TS-negative and 16 TS-positive cases, and 22 DPD-negative

and 32 DPD-positive cases. There was no significant difference between the

patients with TS or DPD and those without TS or DPD in age, gender, histological

type or p-stage. The 5-year survival rates of patients positive and negative for

TS were 50.0 and 89.5%, while 10-year survival rates were 23.3 and 79.7%,

respectively (p

Don't know why, but I have a feeling that the Bone mts in this patient may come from the Lung Cancer, but an 'exjuvantibus' diagnotic approach may be considered, if the Bone lesion improves with AntiAndrogen therapy, it came from the Prostate.

You're right when saying that a Stage I NSCLC may be spared Adjuvant CT, but one millimeter would make a difference, for some a T1aN0M0 NSCLC is not worth giving Adjuvant CT, but a T2N0M0 or a T1bN1M0 may have a benefit from Adj CT, and a T1a is a lump equal or lesser than 2 cm, and a T2 is more than 3 cm but equal or less than 5 cm.

Pathology after Surgery will give a hint about LN condition, and in a case of a woman with Brain mts attending my office, her Oncologist (not me) referred the patient for a Mediastinoscopy, apparently with staging purposes. Would this patient benefit from a PET/TAC? If Positive Nodes are pointed, patient can be spared Surgery on the primary, and just a LN biopsy would suffice for planning therapy.

How reliable are common imaging procedures in assessing the T in a NSCLC before surgery or other primary tumor therapy? I haven't focused on this.

I'd check Vit D levels, eventually correct it, and then, after, let us say 10 days, have a Bone Scintigraphy or a Bone Turnover Markers assessment, or both, if not done before, to have data about the baseline situation of bone disease in this patient, Dr Kaniklidis made elsewhere in this site a throrugh and very practical review of available methods of Bone Disease Assessment in Cancer patients.

An Skeletal survey by MRI may signal other occult lesions, and mark a target for biopsy of metastatic disease.

A male, with a history of heavy smoking is not probably the person that would harbor EGFR mutations, but the more information you collect about the tumor biology in an individual case, the more chances you'll have of personalizing therapy, even when we know that from the very beginning, Cancer Cells in the primary tumor are not homogeneous in its Biology and/or Drug sensitivity, that changes may exist from primary to metastatic deposits, and even a tumor in a single place may have a different biology depending on the time the biopsy was made, this idea of heterogeneity of tumors, that was the subject of a lectura in e-eso.net, has been in the basis of the concept of switching drugs in maintenance ChemoTherapy of NSCLC, in those cases having achieved a CR, PR or SD after the first 4-6 courses of CT in an advanced NSCLC cases.

Tegafur-Uracil and S-1 are not too different, and there is the case published by C Mendiola et al in Clin Trans Oncol, abstract is elsewhere in this site, who obtained good response with Capecitabine in a woman with metastatic Lung AdenoCarcinoma; after Prog on Cape, patient received another type of drugs, and when Prog was observed again, and Cape re-introduced as single agent therapy, patient had again a response lasting several months.

When Napoleon, once called 'The biggest of astres' and then 'the biggest disaster' was introduced a general with the purposes of considering giving him a power position, he always asked: Well, but, is he lucky?

Dear Jose,

Thank you for all the interesting data and references. really interesting !

However, I have some comments regarding the interpretation of these studies and whether to apply the findings in our practice.

The results of Japanese studies assessing the efficacy of adjuvant UFT are conflicting, some of the positive findings are are based on an exploratory analysis and not on pre-planned analysis, these methodologies require confirmation in other studies. Another issue, I can't imagine why patients with pT1N0 will benefit from adjuvant UFT as was shown in the exploratory sub-analysis as opposed to patients with a higher stage.This is unusual finding if we consider the concept of adjuvant therapy were the benefit is usually identified for the higher risk group.

Another important issue is that these are studies on Japanese patients and we have to be aware that there are possible racial differences, so what applies to Japanese does not necessarily apply to other races.

The data that you presented about predictive markers (DPD expression, mitotic index...etc) for efficacy of adjuvant UFT are really interesting and as you mentioned not all stage 1 NSCLC have the same biology. I think that future studies will focus on identifying subgroups within stage 1 disease that may be candidates for adjuvant therapy.

Regarding LN staging for NSCLC, I think that mediastinoscopy is still standard especially for those with clinical N2 disease when we have to be sure about the nodal status because that may affect therapeutic decisions (surgery or concurrent CRT). There is no doubt that PET scan increased the sensitivity of identifying clinically involved LN, however; the suspected nodal status have to be confirmed through EBUS biopsy or mediastinoscopy before operation. Some patients who are clinically N0 will be upstaged to N2 disease following lobectomy and LN dissection resulting in upstaging of patients from stage 1 to stage 3 disease. For that reason we have to do mediastinal LN dissection from many stations in all NSCLC patients considered for lobectomy because identifying such patients will have not only prognostic, but also therapeutic implications; if a patient with N0 disease on pre-thoracotomy PET scan is upstaged to N2, then that patient will benefit from adjuvant chemotherapy and mediastinal irradiation.