Pseudomyxoma peritonei.

Pseudomyxoma peritonei (PMP) is a rare condition, which is known for its high mortality when not treated properly. The first step to improve prognosis of these patients is to recognize this clinical syndrome preferably in an early stage. Knowledge of pathogenesis and common diagnostic tools is essential in this regard. Treatment strategy for PMP should pursue complete cytoreduction and prevention of recurrence or progression. Combined modality treatment, consisting of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, seems very efficient in this regard. This approach is currently carried out in many centers throughout the world with promising results and seems to win ground as the standard treatment approach.

Learning curve of combined modality treatment in peritoneal surface disease.

BACKGROUND: Cytoreductive surgery with intraperitoneal chemotherapy has emerged as a new standard approach for peritoneal surface disease. This study investigated the learning curve of this combined modality treatment at a single institute. METHODS: Variables analysed over three consecutive treatment periods (1996-1998, 1999-2002 and 2003-2006) included number of abdominal regions affected, Simplified Peritoneal Cancer Index (SPCI) score, result of cytoreduction, morbidity, duration of hospital stay and survival. RESULTS: A total of 323 procedures were performed between January 1996 and June 2006, 184 for peritoneal carcinomatosis of colorectal cancer origin and 139 for pseudomyxoma peritonei (PMP), including second procedures in 11 patients with PMP. The mean SPCI score decreased significantly over the study period (P < 0.001), but the number of regions affected did not. The rate of complete cytoreductions increased from 35.6 to 65.1 per cent (P = 0.012). The postoperative morbidity rate decreased from 71.2 to 34.1 per cent (P < 0.001). The median duration of hospital stay decreased from 24 to 17 days. The peak of the learning curve, graded by the percentage of complete cytoreductions, was reached after approximately 130 procedures. CONCLUSION: The learning curve of combined modality treatment for peritoneal surface disease is long, and reflects patient selection and treatment expertise.

[Pseudomyxoma peritonei; a rare tumour that can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy]. / Pseudomyxoma peritonei; een zeldzame tumor, te behandelen met cytoreductieve chirurgie en hypertherme intraperitoneale chemotherapie.

Three patients, men aged 47 and 30 and a woman aged 48 years, presented with appendicitis-like symptoms, progressive abdominal distension, and an ovarian pelvic mass, respectively. All three were diagnosed with pseudomyxoma peritonei. Treatment consisted of cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC). After a mean follow-up of 64 months (range: 19-89) after initial treatment, the second patient had died of disease progression but the other two were alive and free of disease. Pseudomyxoma peritonei is a rare disease, characterised by progressive intraperitoneal accumulation of mucinous ascites, produced by a mucinous tumour mass on the peritoneal surfaces. The primary tumour is usually a mucinous adenoma of the appendix. Treatment by cytoreductive surgery and HIPEC can result in a 5-year survival rate of more than 80%, depending on the histopathology and the completeness of the cytoreduction. Recognising pseudomyxoma peritonei in an early stage, when complete cytoreduction is still achievable, may result in a considerable improvement in survival.

Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.

AIMS: To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. METHODS: A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. RESULTS: The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. CONCLUSIONS: Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.

Preoperative computed tomography and selection of patients with colorectal peritoneal carcinomatosis for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

AIM: A survival benefit has been observed for colorectal cancer patients with peritoneal carcinomatosis treated by cytoreductive surgery with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). However, this treatment modality is associated with a considerable morbidity and mortality and in a significant number of patients survival is not improved. We studied whether poor survivors could be identified on preoperative computed tomography (CT), in order to avoid unnecessary surgery. PATIENTS AND METHODS: Films of abdominopelvic CT scans from 25 such patients treated by cytoreductive surgery and HIPEC were retrospectively analysed by two radiologists separately. A simplified peritoneal cancer index (SPCI) was used to determine the extent of peritoneal involvement. Correlation between the on preoperative CT based SPCI-scores as well as number of involved abdominopelvic areas (N) and survival was examined with the log-rank test. The relation between each affected region and survival was evaluated with Cox regression analysis. RESULTS: The preoperative SPCI- and N-scores of one of the radiologists had no statistically significant prognostic value, while for the second radiologist SPCI > or = 7 and N > or = 4 were associated with particularly poor outcome. Additionally, the presence of ileocaecal region involvement and, depending on the radiologist, the occurrence of tumour deposits in the left subdiaphragmatic area on CT appeared to be unfavourable prognostic signs. CONCLUSIONS: The prognostic value of preoperative conventional CT appeared to be radiologist dependent and may, therefore, be of limited value in selecting colorectal cancer patients with peritoneal carcinomatosis who will not benefit from extensive cytoreductive surgery followed by HIPEC.

Harm and benefits of short-term pre-operative radiotherapy in patients with resectable rectal carcinomas.

AIM: To weigh the harms and benefits of short-term pre-operative radiotherapy in the treatment of resectable rectal cancer. METHODS: The benefits (reduction of local recurrence) and harm (increase of short-term complications) of short-term pre-operative radiotherapy are balanced using a model which classifies patients in one of five outcome combinations; 1-benefit without additional harm, 2-benefit with additional harm, 3-no benefit, no additional harm, 4-no benefit but additional harm, 5-mortality due to combined treatment. The results of four randomised clinical trials (RCT) which study the addition of short-term pre-operative radiotherapy in rectal cancer were classified according to this model. RESULTS: Five to thirteen percent of the patients have benefit without additional harm of pre-operative radiotherapy, while 0-2% have benefit with additional harm; 74-87% has neither benefit nor additional harm and 6-11% have no benefit but additional harm. A small percentage of patients (1-6%) dies post-operatively as a result of the addition of radiotherapy. CONCLUSION: This model provides a transparent appreciation of the harmful and beneficial effects of any treatment modality investigated by means of a randomised clinical trial. As for short-term pre-operative radiotherapy in resectable rectal cancer is shown, a small percentage of patients benefits from such treatment. Most patients have neither benefit nor additional harm, while a small percentage suffers from additional harm while not receiving any benefit.

Conventional surgery and systemic chemotherapy for peritoneal carcinomatosis of colorectal origin: a prospective study.

AIMS: To report the results of standard therapy for peritoneal carcinomatosis of colorectal origin, which consists of conventional surgery and systemic chemotherapy. METHOD: In a prospective study 50 patients with proven peritoneal carcinomatosis of colorectal origin were treated with conventional surgery combined with 5-fluorouracil and leucovorin, or irinotecan in patients treated by 5-fluorouracil within 12 months prior to entry. Survival and progression-free survival were studied and prognostic factors were analysed. RESULTS: The median survival time was 12.6 months. The median time to progression was 7.6 months. Location of primary tumour and result of conventional surgery and systemic chemotherapy were prognostic factors related to survival. CONCLUSION: The survival time of patients with peritoneal carcinomatosis of colorectal origin seems to be increased in patients treated by conventional surgery and systemic chemotherapy when compared to minimal treatment.

Transverse colon volvulus in children: A case series and a review of the literature.

Volvulus of the transverse colon is very rare in children. Three cases that occurred in a short time span are described and the scarce literature is reviewed. All patients presented with colonic obstruction and in all three the condition was diagnosed at laparotomy, as CT-scanning is not an available option in either of the two institutions. The transverse colon had not become gangrenous but was resected after detorsion for redundancy. The postoperative course was complicated and relaparotomy had to be performed for reobstruction in all cases. Only if the 'reverse' bean sign is recognized on the preoperative plain abdominal radiograph this rare diagnosis can be suspected.

Rationale and techniques of intra-operative hyperthermic intraperitoneal chemotherapy.

BACKGROUND: In recent years surgical cytoreduction followed by intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced as treatment modality in patients with peritoneal surface malignancy. In the current review the rational for this approach, the prerequisites and the different techniques used are discussed. METHODS: A literature search through PubMed was performed. RESULTS: Pharmacokinetic studies have shown an important dose advantage for intraperitoneal versus intravenous application. Hyperthermia enhances the penetration of cytostatic drugs into tumour tissue and also shows synergism with various cytostatic drugs. The penetration depth of drugs into tissue is limited, therefore HIPEC can only be effective in patients with minimal residual disease after (aggressive) surgery. HIPEC can be conducted in various ways, without clear proven advantage of one method over the others. Local complications after this combined treatment approach are mainly surgery related. Intraperitoneal chemotherapy may cause systemic toxicity, dependent on the drug used. In randomised studies cytoreductive surgery followed by HIPEC has proven its value in the prevention of peritoneal dissemination in gastric cancer. Phase II data on HIPEC in peritoneal carcinomatosis of colorectal origin and pseudomyxoma peritonei are promising, but randomised studies are still not available. CONCLUSION: Aggressive surgical cytoreduction and HIPEC in patients with peritoneal surface malignancy has a clear rational and seems to have clinical value.

Adjuvant chemotherapy in a new metastasizing caecum tumor model.

A metastasizing tumour model in which a non-immunogenic tumor (Lewis lung carcinoma) is implanted in the caecum of syngeneic mice, is described. The most interesting property of this model is the formation of spontaneous hepatic and transperitoneal metastases. Resection of the caecum tumor 14 days after implantation leaves micrometastases in liver, peritoneum and lungs. This gives the opportunity for the study of adjuvant therapy. Adjuvant chemotherapy with cyclophosphamide cured a significant percentage of animals with micrometastases in liver and peritoneum. Cyclophosphamide therapy had no effect on micrometastases in liver and peritoneum when the primary tumor was left in place. This finding underlines the importance of aggressive treatment of the primary tumor before adjuvant chemotherapy can be effective in colorectal cancer.

Patterns of failure following treatment of pseudomyxoma peritonei of appendiceal origin.

Pseudomyxoma peritonei is a rare disease caused by a perforated adenoma of the appendix. It results in extensive accumulation of mucinous tumour at specific locations within the abdomen and pelvis. The study was undertaken to examine patterns of recurrence in patients with grade I disease treated by cytoreductive surgery and early postoperative intraperitoneal chemotherapy. After a median follow-up of 1.9 years (range 0.5-7.4 years) 42 out of 118 patients had recurred. In 32 patients, detailed information regarding the anatomical location of recurrent tumour from CT-scan and second-look laparotomy were available and these form the basis of this study. The volume of recurrent tumour was recorded at eight abdominal sites, the laparotomy scar and at suture lines. Patient, tumour and treatment factors were analysed for possible relationship with the pattern of recurrence. With recurrence, true metastatic disease was observed in 3 patients and a distinctly higher grade of intraperitoneal tumour in another patient. Pleural spread of pseudomyxoma was found in 6 patients, always related to entering the pleural cavity during cytoreduction (P = 0.000031). Two abdominal sites consistently had an increase in tumour deposits at re-operation as compared to the initial cytoreduction. Small bowel had large deposits at re-operation in 17% versus 3% at initial cytoreduction and retroperitoneal surfaces 10% versus 0%. Recurrences were most frequent in the left subhepatic/lesser omentum area (28%), while the right subdiaphragmatic area (3%) was least involved. Pseudomyxoma peritonei recurrence in the laparotomy scar was found in 15/29 patients (52%), significantly more frequent if tumour had been present at former laparotomy scars during cytoreduction (P = 0.042). In 15/25 (60%) of patients, recurrences were found at suture lines. Differences in the completeness of cytoreduction, inadequate distribution of intraperitoneal chemotherapy to upper abdominal and small bowel surfaces, and entrapment of tumour within suture lines were thought to be causal factors consistent with this pattern of recurrence. Consequences for future treatment strategies are discussed.

Double dynamic graciloplasty and coloperineal pull-through after abdominoperineal resection.

In patients with a very low rectal carcinoma, an abdominoperineal resection with the creation of a permanent colostomy is the surgical treatment of choice. Creation of a colostomy can be avoided without compromise to oncological safety. The distal colon is pulled through to the perineum and both gracilis muscles are used to create a new sphincter and pelvic floor. These muscles are electrically stimulated by an implanted neurostimulator. Contraction is then no longer dependent upon volition and, due to fibre transformation, the muscle will become fatigue-resistant. The outcome in 11 patients was assessed. After a mean follow-up of 1.3 years, continence was achieved in 7 patients, and 2 patients are awaiting completion of the therapy. In 2 patients, necrosis of the distal colon led to failure of the technique. There was no local recurrence, but 2 patients had distant metastasis. Double dynamic graciloplasty after abdominoperineal resection proves to be an oncologically safe procedure with a reasonable chance of continence and a life without a stoma in the majority of patients.

Breast conserving therapy in patients with relatively large (T2, T3) breast cancers by preoperative irradiation and myocutaneous LD flap reconstruction. A new technique in breast conservation.

We investigated the feasibility of breast conserving treatment (BCT) in patients with large (T2, T3) breast cancers, by combining preoperative radiotherapy and tissue replacement after wide excision by a myosubcutaneous flap transposition. The treatment consisted of 50 Gy whole breast irradiation followed by a 15-25 Gy iridium implant to the primary tumour with 2 cm margins. Four weeks after completion of the radiotherapy, wide excision of the original tumour area with a 1 cm margin and an axillary dissection was performed. In the same session the breast was reconstructed with an ipsilateral latissimus dorsi transposition flap. The treatment results in the first 6 patients are encouraging with respect to treatment toxicity and cosmetic outcome. The clinical tumour response after radiotherapy was difficult to evaluate. However, microscopic evaluation showed residual tumour in all specimens with (focal) involvement of the surgical margins in two. With a minimum follow-up of over 2.5 years no tumour recurrences in the breast have occurred.

Management of bowel obstruction in patients with advanced ovarian cancer.

In a retrospective study, 58 patients with bowel obstruction due to advanced ovarian cancer were analysed. In a forward stepwise proportional hazard regression analysis, we looked for factors influencing bowel obstruction-free survival. Patients who presented with bowel obstruction as the first sign of ovarian cancer and those with a longer interval between last cancer treatment and bowel obstruction did better. Patients with ascites did worse. No other independent factors were found. Based on these data, we classified patients into a favourable prognosis group (no previous treatment or interval since last treatment exceeding 6 months; no ascites) and a poor prognosis group (interval since last treatment shorter than 6 months; ascites). Patients from the favourable prognosis group had a median bowel obstruction-free survival of 8 months, compared to 1 month for the poor prognosis group (P < 0.001). Surgery had a marginally significant positive effect on bowel obstruction-free survival when compared to medical treatment in the favourable prognosis group (P = 0.052). Surgery had no effect at all in the poor prognosis patients.

Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin.

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.

Intraperitoneal cisplatin with regional hyperthermia in advanced ovarian cancer: pharmacokinetics and cisplatin-DNA adduct formation in patients and ovarian cancer cell lines.

The purpose of this study was to investigate the influence of hyperthermia on cisplatin pharmacokinetics and DNA adduct formation. The latter was investigated both in tumour cell lines in vitro and in tumour cells and buccal cells from cancer patients. The patients had advanced ovarian carcinoma and were entered into a phase I study for cytoreductive surgery followed by hyperthermia in combination with intraperitoneal cisplatin administration. The cisplatin-DNA modifications in vivo and in vitro were studied by an immunocytochemical method with the polyclonal antiserum NKI-A59. The patient samples for pharmacokinetic determinations were analysed by flameless atomic absorption spectrometry. In vitro, the combination of hyperthermia and cisplatin enhanced cell killing compared with either treatment alone, such that the cisplatin-resistant ovarian cell line A2780/DDP became almost as sensitive as the parent A2780 cell line (resistance factor reduced from 30 to 2 at the IC50). In addition, increased cisplatin-DNA adducts were observed in the resistant cell line after the combined treatment compared with cisplatin alone. A good correlation was found between nuclear staining density and surviving fraction for all groups, indicating that the DNA adducts generated are an important determinant of toxicity and that the mechanism by which hyperthermia enhances kill is by increasing adduct levels. In the patients, the ratio of drug concentration in the peritoneal perfusate compared with that in plasma was found to be approximately 15, indicating a favourable pharmacokinetic ratio. Cisplatin-DNA adduct formation in tumour cells from patients was higher than in buccal cells, reflecting this higher drug exposure, i.e. local plus systemic versus systemic only. In addition, the tumour cells but not buccal cells were exposed to hyperthermia. The higher number of tumour adducts also suggests that a favourable therapeutic ratio could be achieved. Platinum-DNA adduct formation was found to decrease with distance from the surface of the tumour nodules. However, at a distance of 3-5 mm, the nuclear staining density levels were still measurable and higher than in buccal cells. In conclusion, the combined pharmacokinetic and adduct data in patients support the advantages of the intraperitoneal route for drug administration, and the addition of heat.

Thymidylate synthase expression in patients with colorectal carcinoma using a polyclonal thymidylate synthase antibody in comparison to the TS 106 monoclonal antibody.

Colorectal cancer is one of the most common human cancers, for which 5-fluorouracil (5FU) is usually part of the treatment. Thymidylate synthase (TS), the target enzyme for 5FU, can be predictive for the outcome of 5FU-based therapy. TS levels in tumor samples can be determined with radiochemical enzyme assays, RT-PCR, and immunohistochemical staining. We validated TS immunohistochemistry with a polyclonal rabbit anti-human TS antibody using the avidin-biotin method. This antibody can be used on paraffin-embedded, formalin-fixed material using an antigen retrieval method with citrate buffer and microwave treatment. The antibody shows a granular cytosolic staining pattern. The reproducibility in cross-sections from colorectal tumors from 50 patients was 90% and the interobserver variability was acceptable with a kappa of 0.45. On Western blotting it detects purified TS at 36 kD, while in 5FU-treated cells the ternary complex between FdUMP, TS, and 5, 10-methylene-tetrahydrofolate is clearly visible at 38 kD, with no other interfering bands. In a separate set of tumors, immunostaining was compared with enzyme levels; Western blots correlated with enzyme levels. Because both this polyclonal antibody and the monoclonal antibody TS-106 are being used for large-scale studies, we also determined whether they could be used interchangeably. No differences were observed. This polyclonal antibody is specific and gives reproducible results. A study on a larger scale is ongoing to determine the role of TS as a predictive parameter in patients with colorectal cancer treated either with postoperative adjuvant 5FU/levamisole or with surgery only.

Coagulopathy following major liver resection: the effect of rBPI21 and the role of decreased synthesis of regulating proteins by the liver.

This prospective study investigated the role of reduced hepatic synthesis of regulating proteins in coagulopathy after partial hepatectomy (PH) compared with major abdominal surgery (MAS) without involvement of the liver. Furthermore, we studied the effect of rBPI21, an endotoxin-neutralizing agent, on coagulopathy after PH was studied. Compared with MAS, PH resulted in significantly elevated levels of thrombin-antithrombin-III and plasmin-alpha2-antiplasmin complexes. Levels of antithrombin-3, alpha2-antiplasmin, fibrinogen, plasminogen, alpha2-macroglobulin (alpha2-M), and C1-inhibitor remained lower following PH. Treatment with rBPI21 led to significantly lower levels of tissue-type plasminogen activator (t-PA). Post-operative disseminated intravascular coagulation (DIC) was associated with significantly higher bilirubin and t-PA plasma levels and significantly lower levels of alpha2-M. This study indicates that PH induced hepatic failure results in decreased synthesis of hepatic regulating plasma proteins and subsequent activation of coagulation and fibrinolysis. Prevention of t-PA release by rBPI21 may have important clinical implications. Decreased availability of alpha2-M may be a factor in post-operative DIC.

Pulmonary resection for metastases of colorectal origin.

STUDY OBJECTIVE: To develop selection criteria for pulmonary metastasectomy in patients with metastases of colorectal cancer confined to the lungs. DESIGN: A retrospective study. SETTING: Medical records of all patients operated on for this condition in the Netherlands in the period 1982 to 1992 (n = 38). INTERVENTION: Evaluation by means of Cox's proportional hazards regression analysis of factors, which might relate to postthoracotomy disease-free survival and/or postthoracotomy survival. MEASUREMENTS AND RESULTS: The 5-year disease-free survival was 31%, and the overall 5-year survival was 43% (Kaplan-Meyer). Multivariately, a number of three or fewer metastases (p = 0.012) and a short delay between detection of pulmonary metastases and resection (p = 0.05) related to a longer postthoracotomy disease-free interval. A longer interval between resection of the primary tumor and detection of lung metastases related to a longer postthoracotomy survival (p = 0.021). CONCLUSIONS: Patients with three or less pulmonary metastases of colorectal origin may benefit from resection; once metastases have been detected, resection should not be postponed.

The prognostic significance of a previous malignancy in operable non-small cell lung cancer.

There is little data in literature on survival of patients with lung cancer as a second primary (SP) malignancy. This retrospective study was undertaken to investigate whether a previous malignancy has prognostic significance in operable non-small cell lung cancer (NSCLC). Sixty-six patients with SP NSCLC were compared with 75 'first primary' (FP) NSCLC patients without a previous malignancy. All the 141 patients had been surgically treated with curative intent at The Netherlands Cancer Institute (NKI) between 1977 and 1996. Patients who had undergone resections for lung metastases were excluded. Clinical and pathological characteristics were collected and a multivariate analysis on all the 141 patients was carried out. All the previous malignancies were invasive cancers associated with metastatic potential and predominantly located in the aerodigestive tract. Female-male ratio was higher in the SP group (29 vs. 15%, P = 0.06). Tumour diameter was smaller in the SP group (3.0 vs. 4.7 cm, P < 0.0001). Pneumonectomy was performed less frequently in the SP group. Five-year survival rate was higher in the SP group (61 vs. 34%, P = 0.04). Univariate favourable prognostic factors were; small tumour diameter, female gender, favourable pTNM-stage, favourable pT-stage, favourable cTNM-stage, no post-operative radiotherapy and a history of previous malignancy. Multivariate analysis showed tumour diameter, female gender and pTNM-stage to be the major potential confounders. When adjustments were made for these three variables, the prognostic advantage of the SP group disappeared. It was concluded that SP NSCLC has a similar prognosis when compared with FP NSCLC. NSCLC diagnosed during the follow-up of a previous malignancy, and deemed operable, therefore, warrants the same diagnostic and therapeutic approach as NSCLC as first malignancy.