Two characteristics associated with the main colon tumor were discovered to be highly prognostic of survival following recurrence within the analyses from the ACCENT data set presented within this report: initial stage and interval to recurrence. Stage II patients without proof of regional lymph node metastases during the time of diagnosis had longer survival following tumor recurrence when compared with stage III patients. One possible reason behind this observation is the fact that patients with nodal participation during the time of initial diagnosis might be more prone to have subclinical metastases at other sites when compared with individuals without nodal spread. Alternatively, initial regional lymph node participation may signal a biologically different, more aggressive tumor that runs its course more rapidly once recurrence is identified. Your final alternative explanation is the fact that nodal participation during the time of initial diagnosis may reflect the patient is later within the natural good reputation for disease, and also the resulting poorer prognosis is transported forward into prognosis carrying out a recurrence.
Much like tumors that originally present as stage II disease, tumors that don’t recur for lengthy amounts of time following initial management of the main disease have a tendency to behave inside a more indolent fashion following tumor recurrence. The observation that stage III patients who’ve tumor recurrence inside a short time cash shorter survival following recurrence shows that optimal techniques for advanced disease management may vary because of the disparate clinical behavior of the subgroups. It is really an issue that may be resolved by prospective numerous studies. These 4 elements also needs to be taken into consideration within the design and analysis of numerous studies of recent therapies for recurrent cancer of the colon, because the median survival difference of 5.7 several weeks found between patients with initial stage II and stage III disease is bigger than any distinction between regimens studied in phase III first-line trials in advanced colorectal cancer.6-8 Our findings also highlight the significance of sufficient resolution of the lymph node status for patients with early-stage colon cancers.
Patients who have been allotted to receive adjuvant FU-based chemotherapy following surgical resection from the stage II or III cancer of the colon had poorer survival rates following tumor recurrence than did chemotherapy-naïve patients. This can be as a result of selection effect (more aggressive tumors might be determined to recur after adjuvant therapy), a sensitivity effect (tumors relapsing after adjuvant therapy may be not as likely to reply to further treatment during the time of recurrence), or perhaps an imbalance in using chemotherapy after relapse in patients who formerly received adjuvant therapy because of physician desire not to reuse exactly the same chemotherapy then the individual had relapsed. Several caveats should be stored in your mind when thinking about the outcome of prior adjuvant therapy on subsequent clinical course, however. First, our observations relate simply to FU-based adjuvant therapy. No patients within this analysis received adjuvant regimens with newer cytotoxic agents for example oxaliplatin or irinotecan, or targeted therapy with agents for example bevacizumab or cetuximab. Merely a minority of patients within our study had accessibility newer cytotoxic and targeted agents available these days to treat recurrent disease, as reflected within the short survival time following recurrence within this study when compared with expectations in additional contemporary treatment settings. Thus, it’s possible that non–cross-resistant therapy during the time of recurrence might mitigate the negative effects of prior adjuvant therapy we noticed in our study. Later on, investigators may decide to subdivide patients enrolled into advanced disease numerous studies with metachronous metastatic disease into separate strata based on prior receipt of adjuvant chemotherapy, having a third stratum for individuals patients who usual to advanced disease during the time of initial diagnosis.
Survival following recurrence continuously improved from 1978 to 1999, possibly associated with improvement in surgical technique, supportive care, the supply of irinotecan and oxaliplatin to treat recurrent disease in the newest era, or any other factors for example improved diagnostic techniques leading to some lead-time bias. This emphasizes the significance of concurrently randomized numerous studies to evaluate the advantage of new therapies for recurrent disease. Using the current accessibility to several new agents (irinotecan, oxaliplatin, bevacizumab, cetuximab and panitumumab) effective to treat metastatic cancer of the colon6-10 that have been introduced into clinical practice following the timeframe from the ACCENT numerous studies, as well as an growing focus on surgical resection of limited metastatic disease which could prolong survival,11,12 we anticipate that survival following tumor recurrence will improve in the 13.30 days median survival noticed in this analysis. Actually, the lately printed benefits from the GERCOR C96.1 adjuvant therapy medical trial,13 that is incorporated within the ACCENT database, reported an average survival of 24 several weeks from tumor relapse, likely reflecting the outcome of both newer agents and surgical resection to treat metastatic disease.
The analyses presented within this report demonstrate the need for the ACCENT data set to judge clinical prognostic factors in patients with cancer of the colon. It will likely be helpful to include newer adjuvant studies towards the database which include agents for example capecitabine, oxaliplatin, irinotecan, bevacizumab, and cetuximab to make sure that future ACCENT studies will stay highly relevant to contemporary clinical practice.