Recently an approach of waiting after high dose radio-chemotherapy (RTx/CTx) in distal rectal cancer patients (0 to 6 cm ab ano) was reported. The authors discuss this as an option for patients with rectal cancer, please find below the abstract and citation for convenience:
key points:
-n=51 pts
-primary resectable T2-3, N0-1 distal rectal cancer (0-6cm ab ano)
-RTx primary tumor: 60 Gy (in 30 fractions)
-RTx lymph nodes 50 Gy in 30 fractions & 5Gy boost)
-CTx: oral tegafur-uracil 300 mg/m² every weekday for 6 weeks
-Median Follow-up 23.9 months
-local recurrence rate 15.5%
Background
Abdominoperineal resection is the standard treatment for patients with distal T2 or T3 rectal cancers; however, the procedure is extensive and mutilating, and alternative treatment strategies are being investigated. We did a prospective observational trial to assess whether high-dose radiotherapy with concomitant chemotherapy followed by observation (watchful waiting) was successful for non-surgical management of low rectal cancer.
Methods
Patients with primary, resectable, T2 or T3, N0–N1 adenocarcinoma in the lower 6 cm of the rectum were given chemoradiotherapy (60 Gy in 30 fractions to tumour, 50 Gy in 30 fractions to elective lymph node volumes, 5 Gy endorectal brachytherapy boost, and oral tegafur-uracil 300 mg/m2) every weekday for 6 weeks. Endoscopies and biopsies of the tumour were done at baseline, throughout the course of treatment (weeks 2, 4, and 6), and 6 weeks after the end of treatment. We allocated patients with complete clinical tumour regression, negative tumour site biopsies, and no nodal or distant metastases on CT and MRI 6 weeks after treatment to the observation group (watchful waiting). We referred all other patients to standard surgery. Patients under observation were followed up closely with endoscopies and selected-site biopsies, with surgical resection given for local recurrence. The primary endpoint was local tumour recurrence 1 year after allocation to the observation group. This study is registered with ClinicalTrials.gov, number NCT00952926. Enrolment is closed, but follow-up continues for secondary endpoints.
Findings
Between Oct 20, 2009, and Dec 23, 2013, we enrolled 55 patients. Patients were recruited from three surgical units throughout Denmark and treated in one tertiary cancer centre (Vejle Hospital, Vejle, Denmark). Of 51 patients who were eligible, 40 had clinical complete response and were allocated to observation. Median follow-up for local recurrence in the observation group was 23·9 months (IQR 15·3–31·0). Local recurrence in the observation group at 1 year was 15·5% (95% CI 3·3–26·3). The most common acute grade 3 adverse event during treatment was diarrhoea, which affected four (8%) of 51 patients. Sphincter function in the observation group was excellent, with 18 (72%) of 25 patients at 1 year and 11 (69%) of 16 patients at 2 years reporting no faecal incontinence at all and a median Jorge-Wexner score of 0 (IQR 0–0) at all timepoints. The most common late toxicity was bleeding from the rectal mucosa; grade 3 bleeding was reported in two (7%) in 30 patients at 1 year and one (6%) of 17 patients at 2 years. There were no unexpected serious adverse reactions or treatment-related deaths.
Interpretation
High-dose chemoradiotherapy and watchful waiting might be a safe alternative to abdominoperineal resection for patients with distal rectal cancer.
Appelt AL, Pløen J, Harling H, Jensen FS, Jensen LH, Jørgensen JC, Lindebjerg J, Rafaelsen SR, Jakobsen A: High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015 Jul 3.
http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00120-5/abstract
Björn Brücher Prof.of Surgery
Maybe someone may would say and / or ask, ….
1.
Is it acceptable having high recurrence rates such as 15% in a patient population in rectal cancer patients as the Danish group? This would mean, the report in terms of a therapy strategy would step backwards during the days of local recurrence rates of the regular MILES procedure(?)
2.
Did the Danish group wrongly took into account patients of distal rectal cancer with location between 2-6cm, a patient group which can be treated very effectively and radical by ultra deep anterior resection (?)
3.
Even if scientists would take into account 0-4cm they still would include patients of 4-6cm wrongly into their patient population(?)
4.
Would this be due to improving the results of this trial(?)
5.
The follow up is too short, but let’s stay honest: we all know that the recurrence rates of 90% in CRC patients occur during the first 2 years
6.
But on the other hand their lower range started 15.3 months postoperatively (range: 15.3-31) (?)
7.
Even someone may say, that a lot of cancer centers declare rectal cancer operations as deep anterior resections, although these had not been performed, because the cost pressure is immense: the DRG for deep anterior resection significantly increases the benefit for a hospital (?)
I think that a 15% of local recurrence for distal rectal cancer is too high and worse tah that observed after a radical surgery associated to a neoadjuvant radio-chemotherapy, especially, if it takes in account that all these patients had a complete clinical regression and some of them had a T2 rectal cancer.
Also the rectal function after radiotherapy seems less rhan optimal probably related to an actinic proctitis.
Furthermore, I agree that in the mojority of the patients that respond to the neoadjuvant therapy a sphincter-saving surgery is possible and advisable.
The rational behind the wasteful watching principle in patients complete regression following neoadjuvant radiation and chemotherapy for mid and low rectal cancer is truly alluring. However, a series of issues still need to be addressed with regard with this treatment option.
First:
Thanks to @Francesco and @Peter for your valuable insights, highly appreciated. Of course we have doing anything we can avoiding a rectal exstirpation, however, the radicality may not be overseen and the other undervalued aspect is:
complete response by endoscopy can be masked as tumor cell nests usualy (we learned that in upper GI cancers) are later on within the specimen and a negative biopsy taken after neoadjuvant therapy does not mean there is no tumor rest
There have been a number of publications considering the outcomes of relative survival analysis in such cases. Here, for older patients, with more co morbidity, the higher risk of local recurrence is taken into consideration along with the other competing causes of death. This allows an equipoise to be achieved between the better oncological outcome of radical surgical and the morbidity and mortality of radical surgery. Endreseth and other Scandinavian groups have published widely on this topic. See Outcomes of Rectal Cancer Treatment - Influence of Age in Int J Colorectal Disease (2014) 29:825-834
I think there are some points which I have some difficulties to understand. all you stated that recurrence rate was very high to run with that study. We all know that radical surgery after RCT (APR w/posterior approach, described by Holms) has give less tha 5% recurrence rate. the other one is to make a desicion if complete response has been done in pathologic manner. that is not an easy to be stated without pathologic exam. some series have stated "wach and wait procedure in the patients with T1-T2 tumors or the tumor depth regressed by RCT. the last thing is in my mind a toxicity. in our patient population we have had serious toxicity in the course of regular RT with chemosnsitizer 5FU orally. may be there is lots of things could be written .But it is enough to say at least.
- Badges
- Science topic
- Similar topics
- Geoscience
- Asia
- India