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Introduction
There are over 42,000 new cases of colorectal can- cer (CRC) diagnosed every year in the UK alone, with a third of those being rectal in origin1. Although there has been significant progress in terms of sur- gical technique through total mesorectal excision (TME)2, magnetic resonance imaging (MRI) staging and the multidisciplinary approach overall 5-year survival can still be as low as 17%3. It is estimated that approximately 25% of patients will have he- patic metastases alone at the time of diagnosis4, with 30% having metastatic disease at one or more sites5. Although the management of hepatic metas- tases has advanced with techniques such as radiof- requency ablation6, surgical resection that would not achieve a R0 resection due to locally advanced disease or aggressive metastatic disease renders a patient into a palliative setting.
The World Health Organization (WHO) defines palliative care as an approach that improves the quality of life (QoL) of patients and their families facing the problems associated with life threatening illness through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other prob- lems, physical, psychosocial and spiritual7. The goal of any palliative intervention is to improve the QoL of the patient and / or their family.

Palliative treatment strategies for advanced rectal cancer are often tailored to symptoms, including the potential options of stenting, a defunctioning stoma, localised radiotherapy, laser or argon photocoag- ulation and depending on patient fitness and choice, chemotherapy5. Unlike colonic tumours, they are un- able to be distally bypassed. The decision making for such patients is complex and a multidisciplinary team approach is needed for the choice of treat- ment based on the patients’ symptoms, age, extent of disease and performance status. The gold stand- ard treatment for locally advanced T4 rectal tu- mours is long-course chemoradiotherapy (LCRT) in an attempt to achieve clear surgical margins, fol- lowed by resection.8 This, however, is associated with the high morbidity of pelvic dissection, impact on urinary and sexual function, anastomotic dehis- cence and significant QoL factors, and so is often avoided in patients with palliative advanced meta- static disease.

Through the recent COVID-19 pandemic there was a significant reduction in patients actively seeking healthcare advice and therefore being referred for investigation and diagnosis9. This has resulted in a greater number of patients being diagnosed with advanced disease, and often presenting as an emergency, increasing the burden of patients pro- ceeding down a palliative route. As a bridge to re- section once the underlying COVID-19 knowledge base was built and green pathways were estab- lished, alternative oncological strategies were em- ployed, particularly in the form of short-course ra- diotherapy10,9. Although the short-term evidence appeared safe, the long-term effects of this are yet to be fully established11. Over the past 15 years, there has also been a notable trend towards younger patients presenting with higher rates of distal tumours, particularly in the 20-29 years age range12. Both of these temporal changes raises the scenario of patients with a good performance status having a high physiological reserve to undergo pel- vic surgery, even in the advanced metastatic dis- ease palliative setting. In this systematic review we aim to evaluate the cur- rent evidence for the role of palliative primary tu- mour resection and impact on overall survival.

Methods
A literature search was performed for full text arti- cles using the PubMed, Cochrane databases. The search criteria string used was ‘(Rectal cancer OR rectal malignancy OR rectal carcinoma) AND (Pal- liative surgery OR palliative resection) in March 2022.
Additional papers were detected by screening the references of relevant papers. Relevant titles were included in the search results, and those papers where then read through in full. The focus was lim- ited to patients with rectal cancer however all study types were included in the search. Exclusion criteria included those reporting cancer elsewhere in the co- lonic tract alone, full article texts not available in English and articles prior to 1980.Once the papers were identified, a search was per- formed to exclude duplicated results or duplicated data sets to produce a final list of papers. The re- view was registered on the PROSPERO database (CRD42022322631). A summary of the papers in- cluding is displayed in the PRISMA diagram in Fig- ure 1. Bias was assessed using the Joanna Briggs Institute checklist (see appendix).

Results
A total of 7 papers were deemed eligible and in- cluded in the review. They were all retrospective cohort studies in nature, with an overall high risk of potential bias on scoring. In total 809 patients were included, all of whom underwent primary rectal cancer resectional surgery in the palliative setting
with or without adjuvant therapy. A summary of the studies included in the review are displayed in Table 1.

Demographics
The median age at primary resection was 61 years, with a range of 54-64 years. The predominate gender was male comprising of 59.7% of the study population. The most commonly reported symptoms pre-operatively were bleeding per rectum and te- nesmus, however other symptoms included a change in bowel habit, pelvic and abdominal pain, weight loss and anorexia. Twenty-one patients presented with obstructive symptoms. 68.8% of patients pre- sented with liver metastasis at the time of diagnosis, with lung and peritoneum being the second two most common sites for metastasis.Only 3 papers report the TN20 staging of the pri- mary tumour, which are demonstrated in Table 2. The most commonly reported tumour grade was T3 and nodal status N1 across those reported.

Neoadjuvant therapy
Across the studies, 4-50% of patients in each cohort underwent neoadjuvant therapy prior to their sur- gery. Al-Sanea et al 13 reported 11 patients receiv- ing neoadjuvant therapy; 9 of those in the form of radiotherapy and 2 chemotherapy. Longo et al15 in- cluded 3 (4.0%) patients receiving radiotherapy, and Nash et al17 4 (5.0%) patients receiving chem- otherapy. Of interest the predominant neoadjuvant therapy that was reported was radiotherapy, with a smaller subset of patients receiving chemotherapy upfront.

Operative technique
Graph 1 demonstrates the various operative ap- proaches that were employed for the resection of the primary tumour. Six out of the 7 papers re- ported the specific procedure employed. The most common surgical approach was an anterior resec- tion, consisting of 59.9% of all operations. An ab- dominoperineal resection (APR) accounted for 27.9% and lastly a Hartmans for 12.2% There were no pelvic exenterations performed.

Morbidity
Across the studies examined 15-54% of patients were reported to have had a post-operative com- plication, with a return to theatre rate of 5-14%. Kleespies et al 18 reported that 54.5% of their pa- tients developed post-operative complications. The most common being a superficial wound infection for 27.3% followed by anastomotic leak at 24.2%. Incisional hernia, post-operative bleeding and ab- scess formation accounted for 16.3%, 6.5% and 4.3% respectively. 14.3% required a return to the- atre, with a median length of stay (LOS) of 15 days. Similarly, Heah et al 14 reported an overall compli- cation rate of 40.7%, however with a short median LOS of 8 days.Longo et al15 identified pelvic sepsis as the highest post-operative complication, with an overall rate of 26.4%. Two patients required an emergency lapa- rotomy, one for intra-abdominal sepsis for an anas- tomotic leak following stapled anastomosis for a low anterior resection, and the second for pelvic bleeding.

Nash et al17 stated that 15.0% of their patient co- hort developed complications. 5.0% underwent a return to theatre, for again either an anastomotic leak or pelvic bleeding. Other complications that were managed conservatively included 3 pelvic ab- scess that where drained percutaneously. The me- dian LOS for this study was 9 days with 7 patients requiring readmission within 60 days.Verberne et al16 classified their 38.0% complica- tions into either minor or major. Minor included uri- nary retention (n=3), urinary tract infections (n=1) and pulmonary infection (n=1). Major complications included respiratory insufficiency requiring ventila- tion (n=1), septic shock with multiorgan failure (n=1) and fascial dehiscence (n=1). The mean LOS in this study was 17 days, exceeded only by Al-Sanea et al. 13 at 18.6 days.

30-day Mortality
The highest 30-day mortality reported was Longo et al 15, at a rate of 7.3%. This was followed by Longo et al15 at 6% , Kleespies et al 18 at 3.9% and Nash et al17 at 1%. Advancing age, high ASA score, T4 stage of tumour and post-operative com- plications correlated with an increased 30-day mortality.

Adjuvant therapy
The use of adjuvant therapy was reported in all 8 papers. Al-Sanea et al 13 was the only cohort not to report the use of chemotherapy, however 36.3% of patients received post-operative radiotherpy, four patients had radiotherapy for symptom control, two for bony metastasis, one for liver metastasis and one for peritoneal metastasis. Heah et al 14 report 50.0%, 7.4% and 20.3% of their patients receiving chemotherapy, radiotherapy and chemoradiother- apy respectively, they don’t however specify the lo- cation of the adjuvant radiotherapy. Longo et al 15 report 66.1% of their patients receiving adjuvant therapy but don’t provide a breakdown of the same or to the site provided. Verberne et al 16 and Nash et al17 report 58.0% and 76.2% respectively of their patients received chemotherapy only. Nash et al17 goes further to report that three patients re- ceived Hepatic arterial infusion chemotherapy and one received intraperitoneal chemotherapy. Kleespies et al18 demonstrated that 66% of their patients received chemotherapy only and another 22.1% received a combination of chemoradiother- apy. Sigurdsson et al 19 was the study with the greatest population size and they report 43.9% of these patients receiving chemotherapy alone and 20.5% receiving radiotherapy. The site of radiation however hasn’t been stated. As can be seen from the data the majority of patients received chemo- therapy, which is in line with literature that supports the use of chemotherapy in the presence of ad- vanced or metastatic disease. Radiotherapy is often used in the preoperative setting to help with symp- tom relief however it has no effect on the long-term survival of these patients.

Survival
Longo et al 15 reported 1-year survival of 65%. They observed no difference between survival of patients with advanced local invasion compared to patients with local metastases, however they did note a difference in patients with distant metastasis who survived significantly shorter periods of time compared to those with local invasion. Between their resected and non-resected group of patients with locally advanced disease they noted that patients who underwent resection survived significantly longer that the patients who were treated without resection, with 1-year overall survival (OS) 65% v 20% and 2-year OS 20% v 0%. The overall local recurrence rate reported was 6% with a median time of 20 months.

One-year survival across the Kleespies et al 18 co- hort was 56.7%, with independent prognostic fac- tors for reduced survival including a large tumour burden such as high pT stage, positive lymph nodes, positive local resectional margins, lack of postoper- ative tumour specific therapy and most significantly >50% hepatic parenchymal replacement. There was no association between OS and age, sex, symptoms, primary tumour site (colon or rectum), comorbidity of patients, metastatic spread (to more than one organ) or type of surgery (oncological vs segmental). Three-year survival was 5.9%. Al-Sena et al 13 reported 13.64% of patients surviving 3 years.

Verberne et al 16 also reported a significantly bet- ter OS for patients undergoing resection compared to those not. Resection of the primary tumour fol- lowed by chemotherapy led to a longer survival of patients that was independent of age, comorbidity and extent of disease. They report a 3.84% 3- year survival. The highest 5-year survival was reported by Al- Sanea et al 13 at 5.0%, however with a note as to the lower mean age of their patients and lower morbidity and mortality rates. Kleespies et al 18 re- ported a 1.5% 5 year survival, with Longo et al 15 a rate of 0.0%.

Discussion
Although the data across the literature for patients undergoing primary rectal resection with a pallia- tive intent is limited to only 7 papers, it is evident that the procedure is being carried out. Due to the nature of the disease, small cohorts and potential poor long-term outcomes, it is conceivable that there is under reporting of data that is desperately re- quired to add to the field. The highest 30-day mor- tality reported was by Longo et al 15, at a rate of 7.3%, followed by Kleespies et al 18 at 3.9%, demonstrating that the procedure can be consid- ered relatively safe in this high-risk cohort. Across the studies examined 15-54% of patients were re- ported to have had a post-operative complication, with a return to theatre rate of 5-14%. The most commonly reported complications included superfi- cial wound infections and anastomotic leaks. Alt- hough conferring the benefits of the avoidance of stoma related morbidity, given the likelihood of these patients progressing to adjuvant chemother- apy and potential underlying limited physiological reserves the potential avoidance of an anastomosis, with careful counselling of the patient, may in fact be a safer option.

The most commonly reported pre-operative symp- toms were rectal bleeding and tenesmus. Heah et al14 stated that patients reporting bleeding, tenes- mus and diarrhoea symptoms were effectively elim- inated in the post-operative period, however this was not the same across the board. Al-Sanea et al13 also reports that the patients in their cohort also ex- perienced minimal symptoms despite their progres- sive disease and they account a proportion of this to a well set up palliative community support post operatively. Longo et al15 demonstrated that only 4% of their patients developed significant pelvic pain in the resected group compared to 14% in the non-resected group. They go on to comment that the overall QoL seemed better when palliative resec- tion could be accomplished because of better con- trol of pelvic disease, although no formal assess- ment was made. There is no formal assessment of QoL across our literature and therefore robust data in this regard is lacking and does not allow us to draw any conclusions within this paper.

Heah et al 14 looked at the difference between pa- tients undergoing an APR and a Hartmann’s proce- dure. They found that patients undergoing an APR had the main added complication of sepsis from the perineal wound. Half of patients reported wound infection and one third persistent post-operative perineal pain, highlighting the need for careful op- erative consideration and patient counselling. The type of operation performed could play an im- portant part in the post operative recovery and as- sociated morbidity. Contrary to this however the re- cent HiP study21 done in 2020 demonstrated that there was no difference in the rate of complications between patients who underwent a Hartmans pro- cedure vs intersphincteric APR. They demonstrated that serious perineal wound infections were lower than serious pelvic abscess and that the emotional wellbeing component of the FACT-C questionnaire was lower in patients who underwent the APR at 90 days compared to the other subgroup.

Longo et al 15 reported an overall 1-year survival of 65%, with patients who underwent resection sur- viving significantly longer than those without; 1- year OS 65% v 20% and 2-year OS 20% v 0%. Verberne et al 16 also reported a significantly bet- ter OS for those undergoing resection, with a 3.84% 3 year OS. They found that resection of the primary tumour followed by chemotherapy led to a longer survival of patients that was independent of age, comorbidity and extent of disease. The highest 5-year survival was reported by Al-Sanea et al 13 at 5.0%, although their cohort was noted to be at a younger age range and lower post-operative mor- bidity, again highlighting the importance of careful patient selection and intra-operative decision mak- ing. This data directly comparing the 2 oncological strategies is limited, although encouraging for re- ducing disease burden.

As a major limitation of our review, the most recent included paper was published in 2010. The man- agement of rectal cancer, in terms of accurate dis- ease staging, surgical approach and technique has progressed significantly during that time period and brought with it improved overall outcomes. There have been significant recent developments in the management of patients with rectal cancer. Op- erative techniques including laparoscopic and ro- botic approaches now dominate the field as they are hypothesized to provide better access to the pelvis, particularly in the obese male population22. In the palliative setting an early discharge and re- turn to independence should be considered a key goal and minimally invasive techniques have been demonstrated to provide this.23 With the introduc- tion of the enhanced recovery after surgery (ERAS)24 protocol we have also reduced length of hospital stay and post-operative complications. More up to date data is required to fully assess re- sections being performed with a palliative intent in the current setting to get a better idea of short and long-term outcomes. The most commonly resected tumour across the cohort was T3N1 disease, demon- strating a good intent to achieve clear surgical mar- gins, but potentially under-representative of all suit- able patients. The age range is also limited to 54- 64 years, which may exclude patients who are po- tential candidates and introduce bias into morbidity rates. The ideal primary endpoint of any palliative study would be impact upon quality of life, however the lack of data within our literature prevents us from drawing any meaningful conclusions.

With a growing cohort of patients being diagnosed with both advanced disease and at a younger age changing the rectal cancer landscape, it is impera- tive that we build a more established evidence base for any oncological approach that may convey a safe means of improving overall survival and good QoL. Due to the nature of the disease, and level of heterogenicity, collecting large scale randomized data may be impossible. A multi-centre national prospective database may however be achievable with careful planning to help draw firmer conclu- sions from the data moving forward.

Conclusion
In conclusion, this systematic review has demon- strated that palliative resection for rectal cancer is indeed beneficial in a select group of patients. The main benefits of offering this cohort of patients re- sectional surgery is to manage palliative symptoms and improve their quality of life. However, it is shown that patients who underwent surgery had a longer survival as compared to the cohort that didn’t. One study reported that they were able to offer adjuvant chemotherapy thereby increasing their length of survival. With a relatively low 30 day mortality, palliative surgery is seen to be safe in this higher risk group of patients. More recent studies have shown no difference in the type of surgery offered to the patient. A limitation of this paper is that the most recent data is from 2010, since then there has been great developments in surgical techniques and enhanced post operative recovery. More recent data would be required to fully assess resections that have been done in a palliative set- ting and to formally address the impact of quality of life in this cohort of patients. We propose a multi- centre national prospective database to achieve formal conclusions from the data in the future.

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