Oncological outcomes and quality of life after rectal cancer surgery

1 Introduction

Rectal cancer surgery has been completely revolutionized in recent decades. The Total Mesorectal Excision (TME) concept with neoadjuvant chemo-radiotherapy has significantly improved oncological outcomes, especially in terms of local recurrences [1, 2, 3]. Before TME surgery, local recurrences reached up to 25% [4]. Nowadays their rate is generally lower when TME surgery is associated with radiotherapy [5]. On the other hand, overall survival has not shown the same benefits from the improved disease control as it is primarily influenced by the risk of distant metastasis.

Despite the significant improvements of treatment strategies and oncological outcomes, surgeons are currently challenged by patients’ need for a better quality of life. In fact, regardless of the possibility of recovering from cancer, patients are often frightened by the surgery itself: rectal cancer surgery is generally considered as highly destructive due to the risk of definitive colostomy, incontinence, sexual and urinary dysfunctions, alteration of body anatomy, and overall poor quality of life.

The introduction of new technologies and surgical approaches is the surgeons’ attempt to address these patients’ needs. Today, technology has a strong impact on the management of colorectal malignancy, starting from the availability of new diagnostic tools that allow an early diagnosis. In this regard, a crucial role is played by new endoscopic devices [6]. Future scenarios include the possibility of an “in vivo” histology and an early diagnosis during the endoscopic examination through the so called “augmented endoscopy”. For example, the clinical implementation of confocal laser endomicroscopy (CLE), allows the study of tumours’ vascular models and even to detect early dysplastic lesions [7,8].

Laparoscopy, Robotic, Transanal Total Mesorectal Excision (Ta-TME) and Transanal Minimally Invasive Surgery (TAMIS), are current approaches that perform minimally invasive procedures for rectal cancer surgery. They have been proposed mainly to overcome technical challenges in difficult pelvic dissections, but no evidence exist to date demonstrating that such techniques provide benefits in functional and oncological results, other than improving cosmesis and offering better recovery outcomes.

In this review, we will discuss the current advances of rectal cancer surgery, trying to emphasise the rationale of new techniques and surgical approaches, also on the basis of anatomical and histological considerations, as well as patients’ quality of life related issues.

2 Laparoscopic surgery for rectal cancer

Current rectal cancer treatment is based on multimodal management and essentially on chemoradiotherapy and surgery with total mesorectal excision (TME) [9]. TME has become the gold standard for rectal cancer despite the best surgical approach (laparotomy, laparoscopy, robotics, etc.) being still debated, especially for complex cases (obese patients, T4 tumors, very narrow pelvis etc) whereas laparoscopic surgery is sometimes technically demanding. Indeed, data concerning the role of minimally invasive approaches to rectal cancer treatments are sometimes still controversial. On the other hand, the results of several multicentre randomized trials have demonstrated that laparoscopic colon cancer treatment provided benefits in terms of cosmesis, short term outcomes and recovery parameters, with oncological outcomes not inferior to those provided by open surgery [10,11]. Colon cancer laparoscopy has also produced high-quality specimens and is shown to be safe even if performed by surgeons in training [12,13]. The same level of evidence and the benefits of laparoscopic surgery have not been clearly demonstrated in the field of rectal cancer surgery.

Potential benefits of laparoscopy in the surgical treatment of rectal cancer are the same as for colon cancer, namely: shorter hospital stay, reduced intraoperative blood loss, smaller surgical scars, less pain after surgery, faster return to normal activity, and reduced risk of infection without any increase of perioperative mortality.

Data from literature are also difficult to interpret considering that many studies comparing open versus laparoscopic surgery do not include large tumours such as T4 or T3 tumours closer than 2 mm from the endopelvic fascia before neoadjuvant treatments (which often occur in anterior tumors) [14]. On the other hand, some literature reports suggest that T4 colorectal cancer should not always represent an absolute contraindication to laparoscopic approach, making the matter even more confusing [15].

3 Robotic surgery for rectal cancer

Rectal cancer laparoscopy has not achieved the success it deserves despite the remarkable development of minimally invasive surgery in recent decades. This is probably due to the technical complexity of TME, the very steep learning curve for young surgeons, and of the complex pelvic anatomy. Robotic surgery has the appeal of overcoming these fundamental limits thanks to its three-dimensional vision together with better ergonomics and superior precision of TME due to the robotic arms technology. Total mesorectal excision with transection of the rectum at the anal canal is usually required for middle and lower rectal cancers. With regard to the upper rectum tumours, PME (partial mesorectal excision) is usually adequate even though you have to preserve an intact mesorectal fascia, ensuring a 5-cm distal mesorectal resection margin [25,26]. On the other hand, coloanal anastomosis with intersphinteric resection is a reasonable alternative for very low tumours if they do not invade the pelvic floor muscles. It preserves sphincter function, thus avoiding abdominoperineal resection (APR), and allows a good quality of life; these techniques have been described in minimally invasive as well as in open procedures [27,28].

Two main approaches are usually adopted for robotic assisted TME: the hybrid technique and the full robotic.

The hybrid technique consists of laparoscopic mobilization of the left colon plus splenic flexure mobilization followed by robotic total mesorectal excision. The totally robotic resection is carried out with the aid of the four-arm Da Vinci’s robotic system. The patient is placed in lithotomy position while the robot is docked at the patient’s left side. The operation begins with the medial to lateral mobilization of the left colon, with the high ligation of the mesenteric vessels. Once the left colon and the splenic flexure are completely mobilized, the pelvic TME dissection begins. Rectal transection is usually performed laparoscopically with a linear stapler. The specimen is taken out through a supra-pubic mini-laparotomic access; in the end, a laparoscopic coloanal anastomosis is then perfomed [29].

The first study on robotic TME was led by Pigazzi et al. [30] in 2006. In this study the authors compared the laparoscopic approach with the new robotic technique. In particular, they compared the results in 6 patients undergoing laparoscopic rectal resection with six patients operated using the robot. Regarding short-term outcomes, the operative time was similar for the two groups (4.3 hours versus 4.4 hours), while the operative blood loss was higher in the laparoscopic group (150 cc vs 104 cc); shorter in-hospital stay was reported for patients undergoing laparoscopy (3.6 days vs. 4.5 days). After this preliminary experience, the authors deduced that robotic surgery has the ability to get less demanding rectal dissections that is especially beneficial to young surgeons trained in minimally invasive colon surgery.

Overall, literature data dealing with safety, feasibility and outcomes after robotic rectal surgery are often controversial and a definitive answer regarding the best approach for surgical treatment of rectal cancer probably does not exist to date.

4 Transanal total mesorectal exicision (TaTME)

Trans-anal Total Mesorectal Excision (Ta-TME) was firstly introduced by Lacy et al. in 2010 [36,37]. It is based on the combination of minimally invasive abdominal and perineal approaches to complete the distal rectal dissection in order to overcome those technical issues which are typical of both laparoscopic and robotic rectal surgery.

As stated by the St. Gallen Colorectal Consensus Expert Group, TaTME would be preferably indicated in cases of mid-distal bulky tumours, obese patients and narrow pelvis. It has the potential benefit of an easier intersphincteric resection - when indicated - and a better nerve preservation thanks to an appropriate view of distal rectum, especially its intra-elevator part, which is known as the “no man’s land”. Nevertheless, this procedure has some drawbacks as emphasized by preliminary reports: dissection in the proper anterior plane might be tricky, with the risk for urethral, vaginal or prostatic injuries [38]; moreover, an appropriate learning curve is obviously required [39], because of the loss of the usual anatomic landmarks, as the distal resection starts from below.

Data from selected series and their meta-analysis encourage this novel approach, even in terms of short-term oncological “surrogate” outcomes. A 2016 meta-analysis reports a better circumferential margin after TaTME with a lower CRM positivity rate and an overall higher TME quality according to Quircke’s criteria [40]. A more recent meta-analysis by Jian et al. concludes that TaTME would be able to achieve a longer distal resection margin (DRM) when it is compared to laparoscopy [41]. Such result might be explained by the advantages of pneumo-dissection, in that the right anatomic planes can be found by better visualization of the distal margin of the tumour (from the luminal side of the rectum before the dissection begins). The CRM positivity rate significantly decreased also in the Bordeaux’ prospective randomized trial which enrolled 100 patients even though, perhaps surprisingly, the 5-year local recurrence rate (2,6% in the TaTME group vs 4,8% in the Lap group) and the 5-year OS were not significantly affected by the surgical approach [42]. Post-operative major morbidity is also comparable with laparoscopic surgery by considering similar rate of postoperative ileus, anastomotic leak and urinary dysfunction.

More robust evidences from multicentre RCTs are certainly advocated to definitively establish the role of TaTME in clinical practice. Hopefully, the long term results of the COLOR III trial [43] and the ETAP-GRECCAR 11 TRIAL [44] will provide these required answers.

5 Quality of life: what’s the role of novel technologies?

Quality of life is a priority in modern rectal cancer surgery especially the preservation of postoperative function [45].

Preservation of sphincter function after an ultra-low colorectal, coloanal, inter-sphincteric or even a pull-trough procedure has certainly decreased the patients’ fear for surgery and postoperative impact of surgery itself on social life [27,28,46,47].

The construction of a temporary ileostomy is generally advocated by most authors in case of ultra-low resection or coloanal anastomosis and if its early reversal (usually 8 weeks after primary surgery) is safe. It has a reasonable rate of complications, and is well tolerated by most patients [48,49].

One more frontier of current rectal cancer surgery is the attempt to preserve postoperative urogenital function, namely the adoption of “nerve-sparing” procedures [50]. Nevertheless, the complete preservation of autonomic nerve structures may be unsuitable due to the necessity of an appropriate tumour clearance; thus, a modern-state-of-the-art surgery should aim to pursue the trade off between oncological clearance and function preservation.

Sometimes, patients and tumours characteristics may prevent the possibility to achieve both results, especially in cases of anterior bulky tumours close to or infiltrating the Denonvillier’s fascia, or lateral cancers infiltrating the rectal stalks or pelvic sidewall structures; the same is true for very narrow pelvis especially in obese patients, for previous pelvic surgery and occasionally for radiotherapy.

The identification of the inferior hypogastric plexus and the preservation of hypogastric nerves is considered as the first step to perform good-quality nerve-sparing surgery [51]. On the other hand, emotional, psychological and social elements may also contribute to postoperative sexual and urinary dysfunctions, even if injury of the neurovascular bundle is usually supposed to be the main responsible factor for urinary dysfunction (0-15%) and sexual impairments (10-35%) of patients undergoing TME surgery; moreover, a perfect postoperative function cannot be ensured for all patients even with a meticulous nerve preserving technique [52].

In this context, laparoscopic and robotic surgery have been advocated as potential tools to help in obtaining better nerve preservation and functional outcomes, although results from the literature seem to be quite controversial in this regard.

A subset analysis from the COLOR II trial, for example, comparing open versus laparoscopy, shows no differences in sexual dysfunction and micturition problems [53]. The same seems to be true for robotic; the high magnification and the technical benefits of robotic-assisted approach does not seem to offer better sexual and urinary outcomes when compared to conventional laparoscopic surgery: results from the ROLARR trial do not show statistically significant differences in term of postoperative functional scores (I-PSS, IIEF and FSFI).

On the other hand, Kim et al. led a prospective case-matched study to assess QoL after robotic and laparoscopic surgery [54]. The International Prostatic Symptom Score (I-PSS) was significantly better in the robotic arm at six months; moreover, the I-PSS was comparable to baseline at 6 months in the robotic group and at 12-months in the laparoscopic group. The same was true for the International Index of Erectile Function 5 (IIEF-5) that returned to preoperative level at 6-months in the robotic group and at 12-month in the laparoscopic one

Similar results have been obtained from a meta-analysis by Lee et al. whereas, comparing the I-PSS after robotic and laparoscopic surgery at 3-6 and 12 months, robotic surgery achieved better results at 3 months, although this difference was not maintained by 6 and 12 months [55]. Robotic surgery also scored better in regard to erectile function at 3 and 6 months after surgery.

Finally, Ta-TME needs to be mentioned also for its potential to improve the postoperative functional outcomes; a randomized trial by Pontallier et al. failed to show significant differences in terms of bowel and urinary function between TaTME and conventional laparoscopy, despite a “trend” towards a better erectile function and preserved sexual activity in the transanal group [56].

Kneist et al. showed 10% and 40% of patients having major and minor LARS, respectively, and median LARS score 26 at 6 months after TaTME [57], in one of several studies focusing on intraoperative electrophysiological assessment of hypogastric nerves lesions; on other hand, the median Wexner Score (WS) was significantly higher at month 6 (WS of 7 [moderate incontinence]) after stoma closure than pre-operatively. Outcomes concerning sexual impairment and urinary dysfunction in this study are complex to be objectively interpreted because of the heterogeneity and the small size of the cohort.

Veltcamp Helbach et al. compared Laparoscopic (LAR) and Transanal (TaTME) TME, administered both EORTC QLQ-C30 and C29 questionnaires about QoL, with results in favour of LAR as far as for fatigue, role dysfunction, financial impact, hair loss and faecal incontinence [39]. Items exploring anorectal function in terms of diarrhoea and constipation did not show significant differences, as seen by a LARS score of 24 and 27.7 respectively in LAR and TaTME arm, even considering incontinence to flatus and liquid stool questions. Postoperative IPSS score, female dyspareunia and male impotence were not influenced by surgical approach. When EQ-5D-3L and EQ-VAS was used to analyse overall QoL after TaTME in a prospective cohort study, 1 month outcomes worsened significantly, mostly considering social life impairment, while results show a return to preoperative baseline 6 months after the intervention [58]. This trend was confirmed in EORTC QLQ-C30 questionnaires, excepting for anal pain and social functioning which remained significantly altered at 6 months after procedure. Bladder function, female and male sexual outcomes at 6 months returned to the baseline. Anorectal function analysis showed no significant differences after TaTME, with a major LARS rate of 33.3%, minor LARS in 20%, and no LARS in 46.7% of patients.

Larger multicenter studies are certainly required to obtain definitive answers regarding the role of these novel procedures and their impact on quality of life, possibly overcoming concerns about interpretation of different tests administered, bias related to an adequate learning-curve for TaTME approach, and poor data when female sexual and functional outcomes are analysed.

Potential benefits from novel approaches in rectal cancer surgery might be also analysed from a different prospective: the adequate selection of patients and correct indications for each type of procedure. With this regard, a fundamental role is played by the High-Resolution MRI. Specialists can obtain now detailed information about tumor height, local and venous infiltration, lymph node status. MRI-predicted CRM status presents the same association with Local Recurrences (LR), Disease Free Survival, Overall Survival, than CRM pathologically assessed: we can assume that LR is 20% and 27% in case of MRI-CRM and pathological-CRM positivity respectively, which rises to 32% if both positive and drops to about 7% if both negative [59]. These considerations emphasize the key role played multidisciplinary teams, with the most appropriate choice of the best treatment strategy. From this standpoint a fundamental role is certainly played by preoperative MRI staging, which is able to assess the intersphincteric plane involvement, and enable selection of patients with chance for sphincter-saving surgery. The benefits of optimising medical and surgical management of rectal cancer has been demonstrated by MERCURY II study group [60], showing a reduction to 15% in pCRM involvement, compared to 30% of positivity rate described for low rectal cancer in previous reports.

In addition, MRI pelvimetric parameters correlate with pathologic outcomes influencing short term oncological outcome. Interestingly interspinous distance, and obstetric conjugates in some analysis, seem to predict quality of TME influencing CRM positivity, irrespective from open or laparoscopic assisted approach [61].

6 Conclusions

The patients’ need for a good or at least acceptable quality of life is one of the leading aspect of current rectal cancer surgery. Modern technologies, new surgical procedures, together with a deep knowledge of pelvic anatomy and oncological principles, may help the contemporary colorectal surgeon pursue the proper cancer treatment, without giving up the possibility to preserve both cosmesis and satisfactory postoperative functions. The key could be tailored surgery, where the best technique is chosen on a case by case basis and the experience of the surgeon.