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F. F. Quezada-Diaz and J. J. Smith
Given higher rates of tumor response with some NAT modalities, the need of
TME in patients who achieve a pCR has been questioned, especially when surgery
is associated with late bowel, sexual and genitourinary sequelae that signicantly
impairs the QoL of patients [5, 6].
A Watch-and-Wait strategy (WW) for rectal cancer has been advocated as a treatment alternative for selected LARC patients who achieved a clinical complete
response (i.e., absence of detectable macroscopic tumor by clinical means, cCR).
The implementation of a WW strategy depends on solving current challenges such
as how to correctly identify the best candidates without compromising oncologic safety.
PICO table
Patients
Patients with locally
advanced rectal cancer
treated with
Neoadjuvant Therapy
Intervention Comparator
Clinical and
Pathological
Complete Response
(cCR & pCR)
Total
Mesorectal
Excision
Outcomes
Organ preservation, overall/
disease specic survival, rate
of local/systemic recurrence,
quality of life
Search Strategy
A comprehensive literature search of Cochrane Database of Collected Research,
EMBASE, MEDLINE, and PubMed was performed to identify all the Englishlanguage publications related to locally advanced rectal cancer treated with neoadjuvant therapy and watch and wait/organ preservation strategy from January 2004
until February 2023. The search term strategy included “rectal cancer”, “neoadjuvant treatment”, “organ preservation”, “complete clinical response”, “watch and
wait” and “quality of life”. We excluded studies that did not inform rates of watch
and wait/organ preservation and included only rate of pathological complete
response.
The references of the included studies were reviewed to identify additional studies that were incorporated as appropriate.
Results
Over the last 2 decades, several studies have reported a WW strategy for patients
with LARC after NAT.Most of the data are retrospective case series with the methodological limitations associated with these types of studies [7–15]. A randomized
controlled trial that compares a WW strategy versus TME after achieving a cCR
after NAT is unlikely to be completed or accepted by patients, mainly due the higher
rate of patients that refuse to undergo TME after achieving a cCR.According to
patient-perspective focused studies, 83% of patients would consider a WW strategy
if they achieved a cCR in spite of the potentially higher rate of local regrowth during
the rst 2years of follow-up [16], with up to 30% of patients willing to sacrice
rates of long-term oncological cure in comparison with clinicians [17].
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Several denitions of cCR and pCR exist and have been utilized in both case
series and trials. While stricter criteria may increase the accuracy of individual
patients selected for the WW strategy, more liberal criteria may risk worsening
oncological outcomes. There is only one RCT that validated the use of a three-tier
regression schema to assess response after NAT [18], including digital rectal exam,
magnetic resonance imaging (MRI), and endoscopy. All 3 modalities combined
report an accuracy of 98% to predict absence of tumor [19].
Enhancing response rates to NAT may be associated with higher number of
patients undergoing WW. There is no consensus about which is the best way to
enhance NAT response in LARC.Potential strategies that can be used include: (1)
dose escalation of preoperative radiation therapy, (2) increasing the interval period
after NAT and surgery and (3) administering consolidation chemotherapy after
LCRT or SCRT rather than induction chemotherapy followed by LCRT.
Radiotherapy dose escalation strategies have utilized external beam radiotherapy, brachytherapy, contact radiotherapy and proton/iron beam radiotherapy. A
report of nearly 3300 patients showed that the dose of NAT was a predictor of pCR
[20]. Additionally, neoadjuvant brachytherapy or external radiation therapy boost
did not add a signicant benet in survival or local recurrence when given after
standard NA treatment and TME [21, 22]. The recent phase III OPERA trial that
included early low rectal cancer (cT2, cT3a, cT3b with nodes smaller 8 mm),
showed a 3-year organ preservation rate of 68% (CI 95% 54% to 85%) for tumors
greater that 3cm when treated with chemoradiotherapy and a prior boost of contact
x-ray brachytherapy versus external beam boost [23]. A higher rate of 3-year organ
preservation rate (97%) was observed in smaller tumors (<3cm), but the benet
over local excision alone must be evaluated. In addition, this local therapy is associated with signicant brachytherapy-induced rectal bleeding which requires local
ablative intervention during the rst 3years post-treatment.
A longer delay interval between NAT and surgery is associated with higher rates
of pCR/cCR.The Stockholm III trial showed that waiting 4 to 8weeks after SCRT
was associated with similar tumor regression rates compared to LCRT [24]. An
analysis of a National Cancer Database including stage II and III rectal cancer
patients undergoing LCRT suggested that any surgery interval longer than 8weeks
had higher odds of pCR (odd ratio 1.12, 95% CI 1.01 to 1.25) [25].
The concept of Total Neoadjuvant Therapy (TNT) implies the use of either SCRT
or LCRT and moving the adjuvant dose of systemic chemotherapy into the realm of
NA treatment. It seems that using a consolidation chemotherapy- based total neoadjuvant therapy (TNT) approach is associated with higher rates of response and organ
preservation than using induction chemotherapy. The phase II German trial CAO/
ARO/AIO-12 compared 4cycles of FOLFOX before (induction) or after (consolidation) LCRT.They reported 17% (induction) and 25% (consolidation) pathological complete response rates, respectively [26]. Long term follow-up of this cohort
showed similar results in favor of LCRT followed by consolidation chemotherapy
as the preferred TNT sequence, especially if organ preservation is a priority [27].
Although no WW was offered, patients in the experimental arm of the RAPIDO
Trial (SCRT followed by consolidation systemic chemotherapy) had higher rates of
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F. F. Quezada-Diaz and J. J. Smith
pCR (27.7% vs 13.8%, p-value<0,001) [28]. Updated 5-year data on the RAPIDO
Trial showed that the experimental arm was associated with an increased risk of
locoregional recurrence (10 vs 6%, p= 0.027) whereas the reduction in diseaserelated treatment failure and distant metastases remained similar [29]. The OPRA
trial, in which patients were randomized to induction or consolidation TNT and then
proceeded to surgery or WW depending on response, showed higher rates of organ
preservation in the consolidation arm (58% vs 43%; P 0.01) [18]. These data suggest that higher rates of patients managed with WW may be achieved if consolidation chemotherapy is used over induction chemotherapy followed by LCRT.There
is scarce evidence about the use of SCRT and consolidation chemotherapy as a WW
strategy. In the STELLAR Trial which compared LARC patients treated with SCRT
plus 4 cycles of CAPOX versus chemoradiation, 11.1% of patients in the TNT
group had a cCR with almost all of them (9.4%) undergoing WW [30]. The early
data of the phase II STAR-TREC Trial that compares TME vs SCRT-based organ
preservation vs LCRT-based organ preservation strategies showed promising results
with a 60% of organ preservation at 12months [31]. A non-randomized single arm
trial demonstrated that SCRT followed by 8cycles of FOLFOX was associated with
68% a cCR at 1year follow up [15]. Mismatch repair decient tumors are have
demonstrated better rates of response to NAT specically to PD-1 blockade used in
place of cytotoxic chemotherapy [32]. A summary of the most relevant WW studies
incorporating a WW approach is presented in Table23.1.
Neoadjuvant treatment, especially pelvic radiotherapy, may signicantly affect
the QoL in WW patients. In the Memorial Sloan Kettering published experience,
WW patients report better bowel function when measured by the Memorial Sloan
Kettering Cancer Center Bowel Function Instrument [33]. Hupkens etal., compared
47 WW patients with 41 patients after NAT and TME, showed that QoL was better
in the WW group [34], but a third of the WW patients experienced major low anterior resection syndrome (LARS) as measured by the LARS Score.
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Quality of
evidence
Overall survival, (WW
vs TME)
2 (3%) 100% vs 88% Low
Low
6 (18.8%) 97% vs 100% Low
71 (26.8%) cCR
28 (31%) WW only
32 cCR vs
57 pCR
Moderate
OS: 91% DFS: 68%
OS: 100% DFS: 70%
9 (22.5%) WW Only
2(11%) 1005 vs 92.3% Low
90 (49%) cCR
cCR
18 WW vs 26 cCR
TME
Low
OS: 96.6% DFS: 80.6%
15(15%) WW Only
Retrospective
82 (82%)
61 initial cCR
21 initial nCR
Low
44(34%) 96% vs 87% Moderate
222 (25.2%) WW only
129 WW
Low
OS: 85% DFS: 94%
22 (19.5%) 73% vs 94% Low
808 cCR included
Retrospective
113 WW vs
2 (6%) 5-year overall survival
136 pCR
Retrospective
(continued)
HR 0.212 (95% CI
0.26-1.71, p=NS)
32 cCR
n NAT strategy Study design Regrowth, n(%)
265 LCRT Retrospective
79 LCRT Retrospective
Study
Habr-Gama etal.,
2004 [7]
Smith etal., 2012
Table 23.1 Summary of important WW studies for LARC patients treated with NAT
[8]
183 LCRT Retrospective
51 LCRT (includes brachytherapy) Prospective 40(78.4%)
Habr-Gama etal.,
2014 [9]
Appelt etal., 2015
[43]
LCRT Retrospective
Lai etal., 2016 [11] 44
SCRT: 5%
cCR
100 LRCT: 95%
Martens etal., 2016
[10]
259 LCRT Propensity Match
1009 LCRT: 91% Retrospective
249 LCRT: 31(27%)
Rebehan etal.,
OnCore, 2016 [44]
IWWD Consortium,
2018 [12]
Smith etal., 2019
Induction: 47(42%)
Consolidation: 33 (29%)
Chemotherapy alone: 2(2%)
(FOLFOX)+LCRT
88 TNT Induction Chemotherapy
[13]
Jimenez-Rodriguez
etal., 2021 [14]
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Quality of
evidence
Overall survival, (WW
vs TME)
High
DFS: 78% (Induction)
vs 77% (Consolidation)
Comparable OS
High
100%
(follow up 6 to 25
months)
F. F. Quezada-Diaz and J. J. Smith
98% both groups High
5 (33.3%) 93% vs 67% Very Low
Retrospective
15 cCR
chemotherapy
n NAT strategy Study design Regrowth, n(%)
75
Induction: 42/105
Consolidation:
4 TME
RCT
225 cCR
Induction group: 105
Induction
Chemotherapy+LCRT: 146
304 TNT
33/120
NA DFS 75.1% vs 91.2% High
Consolidation group:
120
RCT
TNT LCRT + consolidation
chemotherapy: 158
120 Organ Preservation: 80 (LCRT:
Organ Preservation:
48(60%)
40/SCRT:40)
TME: 40
None (follow up 6 to
25 months)
12 cCR (100%), only
12 Immunotherapy (Dorstalimab) RCT
23% External Beam
15% Contact X-Ray
Brachytherapy:
MMR decient tumors
RCT
External Beam Boost:
59%
Contact X-Ray
Brachytherapy: 81%
Boost: 74
LCRT+Contact X-Ray
Brachytherapy: 74
148 LCRT+External Beam
Study
Table 23.1 (continued)
Kim etal., 2021 [15] 19 TNT SCRT+Consolidation
Garcia-Aguilar
etal., OPRA Trial,
2022 [18]
Bach etal.,
STAR-TREC Phase
II, 2022 [31]
Cercek etal., 2022
[45]
Gerard etal.,
OPERA Trial, 2023
[23]
SCRT Short Course Radiotherapy, LCRT Long Course Radiotherapy, OS Overall Survival, DFS Disease Free survival, IWWD International Watch and Wait
Database, TNT Total Neoadjuvant Therapy
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Recommendation
WW should be part of the treatment discussion of LARC, considering increasing
rates of cCR with new modalities of NAT, potential quality of life gains, avoidance
of surgical morbidity, and patient preferences (evidence quality moderate, strong
recommendation).
WW should be offered ideally in the context of a prospective trial, if possible,
with a strict protocol and objective assessment standards (evidence quality moderate, strong recommendation). Currently,there are four ongoing trials incorporating
WW for mismatch repair procient tumors in the US, Europe, South America and
Japan [35–37] (Table23.2).
A standardized method for LARC response after NAT should be used, preferably
the three-tiered regression schema from the OPRA trial which includes digital rectal
exam, MRI and endoscopy (evidence quality moderate, weak recommendation).
For patients with LARC who want to maximize the rate of organ preservation,
TNT-based on chemoradiation followed by consolidation chemotherapy should be
recommended (evidence quality high, strong recommendation).
Patients with LARC and MMR-decient tumors, immunotherapy should be considered as part of initial treatment with all patients with rectal cancer undergoing
Table 23.2 Ongoing rectal cancer Phase III RCT with cCR and WW approach as primary
outcomes
Estimated
Study
Yoshino et
al.,
ENSEMBLE
Trial [35]
Smith et al.
(JANUS
Trial [36]
Rödel et al.,
ACO/ARO/
AIO 18.1.
Trial [37]
Habr-Gama
A & Perez
RO et al.,
CCHOWW
Trial [45]
SCRT Short Course Radiotherapy, LCRT Long Course Radiotherapy, OS Overall Survival, DFS
Disease Free survival, TNT Total Neoadjuvant Therapy, cCR complete clinical response, TME
Total Mesorrectal excision, QoL Quality of Life
enrollment Study design
608 TNT
(SCRT+consolidation
CAPOX vs
SCRT+consolidation
CAPOXIRI)
312 TNT
(LCRT+consolidation
mFOLFOX6 vs
LCRT+consolidation
mFOLFIRINOX)
702 TNT
(SCRT+Consolidation
chemotherapy vs
LCRT+Consolidation
chemotherapy)
216
patients
TNT (LCRT +
consolidation 4 cycles
mFOLFOX6 or
XELOX vs LCRT +
consolidation 4 cycles
capecitabine)
Primary
outcome
Organ
Preservation
adapted DFS
at 3 years
cCR rate at 5
years
Organ
preservation
at 3 years
Decision to
WW due to
cCR/
near-complete
response at
18weeks
from last date
radiation
Secondary outcome
ccR rate,
recurrence(type), OS,
distant metastases rate,
QoL
DFS, Organ
Preservation, OS,
adverse events
DFS, cCR, rate TME,
local regrowth, rate
salvage TME, local
recurrence after TME,
QoL
Surgery-free survival,
TME-free survival,
distant metastases free
survival at 3years,
local regrowth-free
survival and
colostomy-free
survival (all at 3years)
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molecular determination of mismatch repair status prior to starting neoadjuvant
therapy (evidence quality high, strong recommendation).
F. F. Quezada-Diaz and J. J. Smith
Personal View
Organ preservation is a valid treatment strategy for patients, who are willing to
accept potentially worse oncological outcomes to achieve this goal. This approach
is also in demand by patients and should be part of the modern colorectal surgeon’s
lexicon when treating and managing patients with rectal cancer.
Our strong preference is that a WW approach is completed in the context of a
clinical trial if possible. Typical WW candidates usually are patients with mid-todistal rectal adenocarcinomas considered for abdominoperineal resections preoperatively or very low stapled/handsewn colorectal/coloanal anastomoses which may
signicantly alter their QoL due to post-operative bowel dysfunction or permanent
colostomy [38].
Currently, the most important challenge in WW is the correct selection of patients
with cCR after NAT.In the perfect scenario, the correlation between patients with a
pCR and cCR should be highly accurate before undergoing TME to safely offer
WW.Real world data shows that up to 25–30% of patients with a cCR experienced
a regrowth of the primary tumor [12], most of them during the rst 2years of follow
up. Notably, up to 15% of patients with an cCR end up having a pCR [7, 19] in the
pathology report.
One of the major uncertainties of WW is the long-term oncologic results [39].
Systematic reviews showed a local regrowth rate between 15.7% and 30% and that
surgical salvage was not feasible in less that 5–8% of the patients [40, 41]. The
International Watch and Wait Database (IWWD) [12] reported a 2-year cumulative
incidence of local regrowth of 25.2%, with most of them diagnosed within the initial
2years of surveillance. The available data from the OPRA trial shows that salvage
surgery for those with local regrowth is feasible, that the oncologic outcomes are
similar for those who underwent TME upfront versus at salvage for regrowth and that
sphincter preservation rates were similar whether patients underwent TME upfront
vs. at salvage (ref OPRA here)– the 5-year updates for this trial show stability on all
outcomes reported at 3 years (data reported at ASCO 2023, Verheij F et al.).
An important concern in patients with apparent cCR, is a potential higher rate of
distant metastasis after tumor regrowth. Data from a 10-year experience at Memorial
hospital suggest a higher rate of distant metastases in patients with local regrowth
when compared to those without local regrowth [13]. Data from the IWWD suggests the same pattern between local regrowth and distant metastases [12]. JimenezRodriguez etal. reported a lower rate of local regrowth (6%) in patients treated with
induction TNT by a single surgeon that actively performed WW [14]. Another publication from the IWWD showed that development of local regrowth at any time is
a risk factor for distant metastases with this risk remaining higher for 5years after
development of local regrowth [42]. Still, whether removing the primary tumor after
completion of NAT would have mitigated this risk is unknown, but this nding
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urges us to develop a WW strategy as part of a standardized clinical protocol. Data
from prospective trials will better inform us on this subject and it is notable that the
introduction of a WW strategy in OPRA was not associated with any oncologic
detriment for the patients in either arm.
WW is a valid and feasible strategy for selected LARC patients, with the challenge still to identify sustained responders by clinical assessment. The OPRA trial
was the rst to integrate WW into a TNT strategy aimed at increasing response
rates, but most of the current evidence for WW is retrospective, making prospectively collected data of great value. NOM or WW strategies should be part of the
treatment discussion of LARC, considering patient interest, patient preference and
acceptance of risk, along with the possible reduction in morbidity with avoidance of
TME.Currently, the best way for patients to utilize WW strategies is in the context
of a prospective trial, if possible, with a strict protocol and objective assessment
standards.
References
1. National Comprehensive Cancer Network. NCCN guidelines: rectal cancer. [Internet]. [cited
2019 Jan 11]. Available from: www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.
2. Smith JJ, Chow OS, Gollub MJ, Nash GM, Temple LK, Weiser MR, etal. Organ preservation
in rectal adenocarcinoma: a phase II randomized controlled trial evaluating 3-year diseasefree survival in patients with locally advanced rectal cancer treated with chemoradiation plus
induction or consolidation chemotherapy, and total mesorectal excision or nonoperative management. BMC Cancer. 2015;15:767.
3. Garcia-Aguilar J, Chow OS, Smith DD, Marcet JE, Cataldo PA, Varma MG, etal. Effect of
adding mFOLFOX6 after neoadjuvant chemoradiation inlocally advanced rectal cancer: a
multicentre, phase 2 trial. Lancet Oncol. 2015;16:957–66.
4. Maas M, Nelemans PJ, Valentini V, Das P, Rödel C, Kuo L-J, etal. Long-term outcome in
patients with a pathological complete response after chemoradiation for rectal cancer: a pooled
analysis of individual patient data. Lancet Oncol. 2010;11:835–44.
5. Ho VP, Lee Y, Stein SL, Temple LKF. Sexual function after treatment for rectal cancer: a
review. Dis Colon Rectum. 2011;54:113–25.
6. Chen TY-T, Wiltink LM, Nout RA, Meershoek-Klein Kranenbarg E, Laurberg S, Marijnen
CAM, etal. Bowel function 14 years after preoperative short-course radiotherapy and total
mesorectal excision for rectal cancer: report of a multicenter randomized trial. Clin Colorectal
Cancer. 2015;14:106–14.
7. Habr-Gama A, Perez RO, Nadalin W, Sabbaga J, Ribeiro U, Silva e Sousa AH, etal. Operative
versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg. 2004;240:711–7; discussion 717–718
8. Smith JD, Ruby JA, Goodman KA, Saltz LB, Guillem JG, Weiser MR, etal. Nonoperative
management of rectal cancer with complete clinical response after neoadjuvant therapy. Ann
Surg. 2012;256:965–72.
9. Habr-Gama A, Gama-Rodrigues J, São Julião GP, Proscurshim I, Sabbagh C, Lynn PB, etal.
Local recurrence after complete clinical response and watch and wait in rectal cancer after
neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat
Oncol Biol Phys. 2014;88:822–8.
10. Martens MH, Maas M, Heijnen LA, Lambregts DMJ, Leijtens JWA, Stassen LPS, etal. Longterm outcome of an organ preservation program after neoadjuvant treatment for rectal cancer.
J Natl Cancer Inst. 2016;108:djw171.
278
https://t.me/medicina_free
11. Lai C-L, Lai M-J, Wu C-C, Jao S-W, Hsiao C-W. Rectal cancer with complete clinical
response after neoadjuvant chemoradiotherapy, surgery, or “watch and wait”. Int J Color Dis.
2016;31:413–9.
12. van der Valk MJM, Hilling DE, Bastiaannet E, Kranenbarg EM-K, Beets GL, Figueiredo NL,
et al. Long-term outcomes of clinical complete responders after neoadjuvant treatment for
rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study. Lancet. 2018;391:2537–45.
13. Smith JJ, Strombom P, Chow OS, Roxburgh CS, Lynn P, Eaton A, etal. Assessment of a
Watch-and-Wait Strategy for Rectal Cancer in Patients With a Complete Response After
Neoadjuvant Therapy. JAMA Oncol. 2019;5:e185896.
14. Jimenez-Rodriguez RM, Quezada-Diaz F, Hameed I, Kalabin A, Patil S, Smith JJ, etal. Organ
preservation in patients with rectal cancer treated with total neoadjuvant therapy. Dis Colon
Rectum. 2021;64:1463–70.
15. Kim H, Pedersen K, Olsen JR, Mutch MG, Chin R-I, Glasgow SC, etal. Nonoperative rectal
cancer management with short-course radiation followed by chemotherapy: a nonrandomized
control trial. Clin Colorectal Cancer. 2021;20:e185–93.
16. Gani C, Gani N, Zschaeck S, Eberle F, Schaeffeler N, Hehr T, et al. Organ preservation in
rectal cancer: the patients’ perspective. Front Oncol. 2019;9:318.
17. Kennedy ED, Borowiec AM, Schmocker S, Cho C, Brierley J, Li S, etal. Patient and physician
preferences for nonoperative management for low rectal cancer: is it a reasonable treatment
option? Dis Colon Rectum. 2018;61:1281–9.
18. Garcia-Aguilar J, Patil S, Gollub MJ, Kim JK, Yuval JB, Thompson HM, etal. Organ preservation in patients with rectal adenocarcinoma treated with total neoadjuvant therapy. J Clin
Oncol. 2022;40:2546–56.
19. Maas M, Lambregts DMJ, Nelemans PJ, Heijnen LA, Martens MH, Leijtens JWA, et al.
Assessment of clinical complete response after chemoradiation for rectal cancer with digital rectal examination, endoscopy, and MRI: selection for organ-saving treatment. Ann Surg
Oncol. 2015;22:3873–80.
20. Hall MD, Schultheiss TE, Smith DD, Fakih MG, Wong JYC, Chen Y-J. Effect of increasing
radiation dose on pathologic complete response in rectal cancer patients treated with neoadjuvant chemoradiation therapy. Acta Oncol. 2016;55:1392–9.
21. Appelt AL, Vogelius IR, Pløen J, Rafaelsen SR, Lindebjerg J, Havelund BM, etal. Longterm results of a randomized trial inlocally advanced rectal cancer: no benet from adding a
brachytherapy boost. Int J Radiat Oncol Biol Phys. 2014;90:110–8.
22. Couwenberg AM, Burbach JPM, Berbee M, Lacle MM, Arensman R, Raicu MG, et al.
Efcacy of dose-escalated chemoradiation on complete tumor response in patients with locally
advanced rectal cancer (RECTAL-BOOST): a phase 2 randomized controlled trial. Int J Radiat
Oncol Biol Phys. 2020;108:1008–18.
23. Gerard J-P, Barbet N, Schiappa R, Magné N, Martel I, Mineur L, et al. Neoadjuvant chemoradiotherapy with radiation dose escalation with contact x-ray brachytherapy boost or external beam radiotherapy boost for organ preservation in early cT2-cT3 rectal adenocarcinoma
(OPERA): a phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2023; https://
doi.org/10.1016/S2468- 1253(22)00392- 2.
24. Pettersson D, Lörinc E, Holm T, Iversen H, Cedermark B, Glimelius B, etal. Tumour regression in the randomized Stockholm III trial of radiotherapy regimens for rectal cancer. Br J
Surg. 2015;102:972–8. discussion 978
25. Probst CP, Becerra AZ, Aquina CT, Tejani MA, Wexner SD, Garcia-Aguilar J, etal. Extended
intervals after neoadjuvant therapy inlocally advanced rectal cancer: the key to improved
tumor response and potential organ preservation. J Am Coll Surg. 2015;221:430–40.
26. Fokas E, Allgäuer M, Polat B, Klautke G, Grabenbauer GG, Fietkau R, etal. Randomized
phase II trial of chemoradiotherapy plus induction or consolidation chemotherapy as total
neoadjuvant therapy for locally advanced rectal cancer: CAO/ARO/AIO-12. J Clin Oncol.
2019;37:3212–22.
F. F. Quezada-Diaz and J. J. Smith
23 Watch andWait Versus Conventional Surgical Treatment inRectal Cancer
https://t.me/medicina_free
27. Fokas E, Schlenska-Lange A, Polat B, Klautke G, Grabenbauer GG, Fietkau R, et al.
Chemoradiotherapy plus induction or consolidation chemotherapy as total neoadjuvant
therapy for patients with locally advanced rectal cancer: long-term results of the CAO/ARO/
AIO-12 Randomized Clinical Trial. JAMA Oncol. 2021;8:e215445.
28. Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM-K, etal.
Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME)
versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy inlocally
advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol.
2021;22:29–42.
29. Dijkstra EA, Nilsson PJ, Hospers GAP, Bahadoer RR, Meershoek-Klein Kranenbarg E,
Roodvoets AGH, et al. Locoregional failure during and after short-course radiotherapy followed by chemotherapy and surgery compared to long-course chemoradiotherapy and surgery– a ve-year follow-up of the RAPIDO trial. Ann Surg. 2023; https://doi.org/10.1097/
SLA.0000000000005799.
30. Jin J, Tang Y, Hu C, Jiang L-M, Jiang J, Li N, etal. Multicenter, randomized, phase III trial
of short-term radiotherapy plus chemotherapy versus long-term chemoradiotherapy inlocally
advanced rectal cancer (STELLAR). J Clin Oncol. 2022;40:1681–92.
31. Bach SP, de Wilt JHW, Peters F, Spindler K-LG, Appelt AL, Teo M, et al. STAR-TREC
phase II: can we save the rectum by watchful waiting or transanal surgery following (chemo)
radiotherapy versus total mesorectal excision for early rectal cancer? JCO Wolters Kluwer.
2022;40:3502.
32. de Rosa N, Rodriguez-Bigas MA, Chang GJ, Veerapong J, Borras E, Krishnan S, etal. DNA
mismatch repair deciency in rectal cancer: benchmarking its impact on prognosis, neoadjuvant response prediction, and clinical cancer genetics. J Clin Oncol. 2016;34:3039–46.
33. Quezada-Diaz FF, Smith JJ, Jimenez-Rodriguez RM, Wasserman I, Pappou EP, Patil S, etal.
Patient-reported bowel function in patients with rectal cancer managed by a watch-and-wait
strategy after neoadjuvant therapy: a case-control study. Dis Colon Rectum. 2020;63:897–902.
34. Hupkens BJP, Martens MH, Stoot JH, Berbee M, Melenhorst J, Beets-Tan RG, etal. Quality
of life in rectal cancer patients after Chemoradiation: watch-and-wait policy versus standard
resection– a matched-controlled study. Dis Colon Rectum. 2017;60:1032–40.
35. Yoshino T.A multicenter randomized phase iii study of short-term radiotherapy plus CAPOX
and short-term radiotherapy plus CAPOXIRI as preoperative treatment for locally advanced
rectal cancer [Internet]. clinicaltrials.gov; 2022 Dec. Report No.: NCT05646511. Available
from: https://clinicaltrials.gov/ct2/show/NCT05646511
36. Alliance for Clinical Trials in Oncology. The Janus Rectal Cancer Trial: a randomized phase
ii trial testing the efcacy of triplet versus doublet chemotherapy to achieve clinical complete
response in patients with locally advanced rectal cancer [Internet]. clinicaltrials.gov; 2022 Nov.
Report No.: NCT05610163. Available from: https://clinicaltrials.gov/ct2/show/NCT05610163
37. Rödel PD med C.Short-course radiotherapy versus chemoradiotherapy, followed by consolidation chemotherapy, and selective organ preservation for mri-dened intermediate and highrisk rectal cancer patients [Internet]. clinicaltrials.gov; 2022 Dec. Report No.: NCT04246684.
Available from: https://clinicaltrials.gov/ct2/show/NCT04246684
38. Emmertsen KJ, Laurberg S. Rectal cancer function study group. Impact of bowel dysfunction on quality of life after sphincter-preserving resection for rectal cancer. Br J Surg.
2013;100:1377–87.
39. Park IJ, You YN, Agarwal A, Skibber JM, Rodriguez-Bigas MA, Eng C, etal. Neoadjuvant
treatment response as an early response indicator for patients with rectal cancer. J Clin Oncol.
2012;30:1770–6.
40. Dossa F, Chesney TR, Acuna SA, Baxter NN.A watch-and-wait approach for locally advanced
rectal cancer after a clinical complete response following neoadjuvant chemoradiation: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol. 2017;2:501–13.
41. Martin ST, Heneghan HM, Winter DC.Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer.
Br J Surg. 2012;99:918–28.
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