Non Operative Management of Patients with Rectal Cancer

Dear Colleagues,

For patients with rectal cancer, cure has been improved in recent decades with the introduction of total mesorectal excision (TME) combined with neoadjuvant radiation therapy, either short or long-course chemoradiotherapy using external beam radiation (n-CTRT). However, for survivors who undergo rectal removal with a permanent colostomy, long-term functional sequelae, including sexual and urinary dysfunction, are documented. In addition, 40% of patients with bowel continuity preservation report a significant reduction in their quality of life (QoL). They also have altered bowel habits in the form of frequency, unpredictability, and fecal incontinence [1–4] for up to 14 years after completion of treatment. More than 20 years ago, in an effort to improve patient quality of life, Habr-Gama pioneered the "watch and wait" (W&W) strategy [5] after n-CTRT for patients with a complete clinical response (cCR) in a cohort of patients bound to have a permanent stoma. This study demonstrated the safety of this method through long-term follow-up data [6], as well as local relapses that can be saved by subsequent surgery, with no apparent negative impact on survival. This treatment paradigm is of growing interest among colorectal cancer specialists worldwide. Validation of its results has since been ongoing.

Two strategies for NOM can be distinguished: one opportunistic, when radio (chemo)therapy is needed as preoperative treatment anyway; the other for small cancers, when preoperative radio (chemo)therapy is not routinely indicated, and the goal of radiation therapy is NOM [7]. While the former strategy is increasingly accepted worldwide, the latter is considered experimental due to lack of data. 

Promising new approaches for improving the rate of patients treated with NMW are emerging—namely, adding a brachytherapy boost (either contact x-ray or HDR) to external beam radiation therapy [8,9,10] or using total neoadjuvant therapy (i.e., adding 3–4 months of sequential neoadjuvant chemotherapy to neoadjuvant radio(chemo)therapy) [11]. Mature data displaying the results of these new approaches are awaited as they will be of utmost importance to patients, especially the elderly with co-morbidities, but also any patient who does not wish to undergo major surgery that could result in a permanent colostomy and/or bowel and sexual dysfunction. These alternative treatment strategies could offer a safe cure with fewer complications.

This Special Issue is dedicated to the most recent strategies with modern chemotherapy regimens and innovative technologies that have explored the NOM avenue, in a joint multidisciplinary effort to improve patient quality of life for a specific patient population using quality imaging.

Prof. Dr. Te Vuong
Dr. Krzysztof Bujko
Guest Editors

References

1. Pucciarelli, S.; Del Bianco, P.; Efficace, F.; Serpentini, S.; Capirci, C.; De Paoli, A.; Amato, A.; Cuicchi, D.; Nitti, D. Patient-reported outcomes after neoadjuvant chemoradiotherapy for rectal ancer: a multicenter prospective observational study. Surg. 2011, 253, 71–77.
2. Nesbakken, A.; Nygaard, K.; Bull-Njaa, T.; Carlsen, E.; Eri, L.M. Bladder and sexual dysfunction after mesorectal excision for rectal cancer. BJS 2000, 87, 206–210, https://doi.org/10.1046/j.1365-2168.2000.01357.x.
3. Peeters, K.; van de Velde, C.; Leer, J.; Martijn, H.; Junggeburt, J.; Kranenbarg, E.K.; Steup, W.; Wiggers, T.; Rutten, H.; Marijnen, C. Late Side Effects of Short-Course Preoperative Radiotherapy Combined With Total Mesorectal Excision for Rectal Cancer: Increased Bowel Dysfunction in Irradiated Patients—A Dutch Colorectal Cancer Group Study. Clin. Oncol. 2005, 23, 6199–6206, https://doi.org/10.1200/jco.2005.14.779.
4. Wiltink, L.M.; Chen, T.Y.; Nout, R.A.; Kranenbarg, E.M.-K.; Fiocco, M.; Laurberg, S.; van de Velde, C.J.; Marijnen, C.A. Health-related quality of life 14years after preoperative short-term radiotherapy and total mesorectal excision for rectal cancer: Report of a multicenter randomised trial. J. Cancer 2014, 50, 2390–2398, https://doi.org/10.1016/j.ejca.2014.06.020.
5. Habr-Gama, A.; Perez, R.O.; Sabbaga, J.; Nadalin, W.; Julião, G.P.S.; Gama-Rodrigues, J. Increasing the Rates of Complete Response to Neoadjuvant Chemoradiotherapy for Distal Rectal Cancer: Results of a Prospective Study Using Additional Chemotherapy During the Resting Period. Colon Rectum 2009, 52, 1927–1934, https://doi.org/10.1007/dcr.0b013e3181ba14ed.
6. Habr-Gama, A.; Gama-Rodrigues, J.; Julião, G.P.S.; Proscurshim, I.; Sabbagh, C.; Lynn, P.B.; Perez, R.O. Local Recurrence After Complete Clinical Response and Watch and Wait in Rectal Cancer After Neoadjuvant Chemoradiation: Impact of Salvage Therapy on Local Disease Control. J. Radiat. Oncol. 2014, 88, 822–828, https://doi.org/10.1016/j.ijrobp.2013.12.012.
7. Gérard, J.-P.; Barbet, N.; Benezery, K. Organ preservation for T2-T3 rectal cancer: opportunistic or planned strategy. Oncotarget 2019, 10, 3431–3432, https://doi.org/10.18632/oncotarget.26916.
8. Appelt, A.L.; Pløen, J.; Harling, H.; Jensen, F.S.; Jensen, L.H.; Jørgensen, J.C.R.; Lindebjerg, J.; Rafaelsen, S.R.; Jakobsen, A. High-dose chemoradiotherapy and watchful waiting for distal rectal cancer: a prospective observational study. Lancet Oncol. 2015, 16, 919–927, https://doi.org/10.1016/s1470-2045(15)00120-5.
9. Benezery, K.; Montagne, L.; Evesque, L.; Schiappa, R.; Hannoun-Levi, J.M.; Francois, E.; Thamphya, B.; Gerard, J.P. Clinical response assessment after contact X-Ray brachytherapy and chemoradiotherapy for organ preservation in rectal cancer T2-T3 M0: The time/dose factor influence. Transl. Radiat. Oncol. 2020, 24, 92–98.
10. Garant, A.; Magnan, S.; Devic, S.; Martin, A.-G.; Boutros, M.; Vasilevsky, C.-A.; Ferland, S.; Bujold, A.; DesGroseilliers, S.; Sebajang, H.; et al. Image Guided Adaptive Endorectal Brachytherapy in the Nonoperative Management of Patients With Rectal Cancer. J. Radiat. Oncol. 2019, 105, 1005–1011, https://doi.org/10.1016/j.ijrobp.2019.08.042.
11. Garcia-Aguilar, J.; Patil, S.; Kim, J.K.; Yuval, J.B.; Thompson, H.; Verheij, F.; Lee, M.; Saltz, L.B.; on behalf of the OPRA Consortium Preliminary results of the organ preservation of rectal adenocarcinoma (OPRA) trial. Clin. Oncol. 2020, 38, 4008, https://doi.org/10.1200/jco.2020.38.15_suppl.4008.

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