Organ preservation or radical surgery? Modern surgical concepts within the complex interplay between function and oncology

A urethral clear cell carcinoma case successfully treated with organ preservation surgery and adjuvant chemoradiation

SummaryBackgroundRadical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision.MethodsTREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743.FindingsBetween Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients.InterpretationShort-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules.FundingCancer Research UK.

PurposeDebate persists regarding the feasibility of adopting an organ-preserving strategy as the treatment modality for clinical T2N0 rectal cancer. This study aimed to compare the outcomes of attempting organ-preserving strategies versus radical surgery in patients with clinical T2N0 mid to low rectal cancer.MethodsPatients diagnosed with clinical T2N0 rectal cancer, with lesions located within 8 cm from the anal verge as determined by pre-treatment magnetic resonance imaging between January 2010 and December 2020 were included.ResultsOf 119 patients, 91 and 28 were categorized into the organ-preserving attempt group and the radical surgery group, respectively. The median follow-up duration was 48.8 months (range, 0–134 months). The organ-preserving attempt group exhibited a reduced incidence of stoma formation (44.0% vs. 75.0%; p = 0.004) and a lower occurrence of grade 3 or higher surgical complications (5.8% vs. 21.4%; p = 0.025). Univariate analyses revealed no significant association between treatment strategy and 3-year local recurrence-free survival (organ-preserving attempt 87.9% vs. radical surgery 96.2%; p = 0.129), or 3-year disease-free survival (79.6% vs. 84.9%; p = 0.429). Multivariate analysis did not identify any independent prognostic factors associated with oncologic outcomes.ConclusionCompared with radical surgery, attempted organ preservation resulted in lower incidences of stoma formation and severe surgical complications, whereas oncological outcomes were comparable. Attempting organ preservation may be a safe alternative to radical surgery for clinical T2N0 mid to low rectal cancer.

Background: Clinical T2 or early T3 rectal cancers can be managed by definitive rectal resection and achieve high clinical complete response (cCR) with chemoradiation, thereby facilitating an intentional watch-and-wait (W&W) or organ-preservation strategy. We assessed the efficacy of neoadjuvant chemoradiation plus consolidation CAPEOX in MRI-defined low-risk rectal cancer to ascertain the proportion of patients who can achieve cCR and receive a W&W or organ-preservation approach. Methods: This prospective, single-arm, phase 2 trial enrolled patients with cT2/T3a/T3b low-risk rectal cancers that were pre-staged by magnetic resonance imaging (MRI), after excluding patients with local or systemic high-risk factors, such as mesorectal fascia, extramural vessel invasion, or mucinous differentiation. All patients concurrently received chemoradiation, followed by four 3-week cycles of the CAPEOX regimen. Following reassessment by the multidisciplinary team, patients with cCR or near-cCR received W&W/organ-preservation surgery. The primary endpoint was the 3-year organ-preservation rate. Findings: Of the 64 participants, 58 completed the treatment, with 6·4% and 33·9% grade 3–4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median follow-up of 32·7 (interquartile range [IQR] 4·3–60·3) months. Initial cCR, near-cCR, and non-cCR occurred in 33 (51·5%), 13 (20·3%), and 18 (28·2%) patients, respectively. Of the 31 cCR and seven near-cCR cases managed by WW 8 and 20 patients received local excision and radical resection, respectively, including six of seven patients with local regrowth salvage. One patient died of postoperative complications. Lung metastasis occurred in one patient with W&W and one patient with local excision, with no local recurrence and an estimated 3-year organ-preservation rate of 68·8%. The estimated 3-year CSS, non-regrowth disease-free survival, and stoma-free survival were 95·8%, 93·8%, and 84·3%, respectively. Interpretation: Chemoradiotherapy with consolidation CAPEOX for MRI-defined low-risk rectal cancer achieves high cCR and organ-preservation rate. Intentional W&W might be a safe strategy for this patient subgroup. Trial Registration: This study is registered at ClinicalTrials.gov with the identifier NCT02860234. Funding: Supported by The Beijing Municipal Science & Technology Commission Capital Clinical Research Special Fund (Z151100004015105); National Natural Science Foundation of China (81773214); Beijing Hospitals Authority Clinical Medicine Development of Special Funding Support, code: (ZYLX202116) Declaration of Interest: None to declare. Ethical Approval: The protocol and the later amendments were approved by the ethics committee of Peking University Cancer Hospital on August 06, 2016 and on December 17, 2018, respectively.

Modified Technique of Radical Inguinal Lymphadenectomy for Penile Carcinoma: Morbidity and Outcome

Background:Organ preservation has been proposed as an alternative to radical surgery for rectal cancer to reduce morbidity and mortality, and to improve functional outcome.Methods:Locally advanced non-metastatic rectal cancers were identified from a prospective database. Patients staged ⩾T3 or any stage N+ were referred for neoadjuvant chemoradiotherapy (CRT) (50–54 Gy and 5-fluorouracil), and were reassessed 6–8 weeks post treatment. An active surveillance programme (‘watch and wait’) was offered to patients who were found to have a complete endoluminal response. Transanal excision was performed in patients who were found to have an objective clinical response and in whom a residual ulcer measured ⩽3 cm. Patients were followed up clinically, endoscopically and radiologically to assess for local recurrence or disease progression.Results:Of 785 patients with rectal cancer between 2005 and 2015, 362 had non-metastatic locally advanced tumours treated with neoadjuvant CRT. Sixty out of three hundred and sixty-two (16.5%) patients were treated with organ-preserving strategies – 10 with ‘watch and wait’ and 50 by transanal excision. Fifteen patients were referred for salvage total mesorectal excision post local excision owing to adverse pathological findings. There was no significant difference in overall survival (85.6% vs 93.3%, P=0.414) or disease-free survival rate (78.3% vs 80%, P=0.846) when the outcomes of radical surgery were compared with organ preservation. Tumour regrowth occurred in 4 out of 45 (8.9%) patients who had organ preservation.Conclusions:Organ preservation for locally advanced rectal cancer is feasible for selected patients who achieve an objective endoluminal response to neoadjuvant CRT. Transanal excision defines the pathological response and refines decision-making.

Rectal cancer is a heterogeneous disease with complex genetic and molecular subtypes. Emerging progress of neoadjuvant therapy has led to increased pathological and clinical complete response (cCR) rates for microsatellite stable (MSS) rectal cancer, which responds poorly to immune checkpoint inhibitor alone. As a result, organ preservation of MSS rectal cancer as an alternative to radical surgery has gradually become a feasible option. For patients with cCR or near-cCR after neoadjuvant treatment, organ preservation can be implemented safely with less morbidity. Patient selection can be done either before the neoadjuvant treatment for higher probability or after with careful assessment for a favorable outcome. Those patients who achieved a good clinical response are managed with nonoperative management, organ preservation surgery, or radiation therapy alone followed by strict surveillance. The oncological outcomes of patients with careful selection and organ preservation seem to be noninferior compared with those of radical surgery, with lower postoperative morbidity. However, more studies should be done to seek better regression of tumor and maximize the possibility of organ preservation in MSS rectal cancer.

To investigate the safety and efficacy of organ preservation surgery or "watch and wait" strategy for rectal cancer patients who are evaluated as clinical complete response(cCR) or near-cCR following neoadjuvant chemoradiotherapy (nCRT). From March 2011 to June 2016, 35 patients with mid-low rectal cancers who were diagnosed as cCR or near-cCR following nCRT underwent organ preservation surgery with local excision or surveillance following "watch and wait" strategy in the Peking University Cancer Hospital. All the patients received re-evaluation and re-staging 6-12 weeks after the completion of nCRT, according to Habr-Gama and MSKCC criteria for the diagnosis of cCR or near-cCR. The near-cCR patients who received local excision and were pathologically diagnosed as T0Nx were also regarded as cCR. The end-points of this study included organ-preservation rate (OPR), sphincter-preservation rate (SPR), non-re-growth disease-free survival (NR-DFS), stoma-free survival, cancer-specific survival (CSS) and overall survival(OS). Kaplan-Meier curve was used to estimate the survival data at 3 years. A total of 35 cases were analyzed including 24 males (68.6%) and 11 females (31.4%). The median age was 60 (range 37-79) years and the median distance from tumor to anal edge was 4(2-8) cm. Thirty-three patients received 50.6 Gy/22f IMRT with capecitabine and two patients received 50 Gy/25f RT with capecitabine. The cCR and near-cCR rates were 74.3%(26/35) and 25.7%(9/35) respectively. Excision biopsy was performed in 4 near-cCR cases to confirm the diagnosis of cCR. The non-re-growth DFS rate was 14.3%(5/35) and the median time of tumor re-growth was 6.7 (4.7-37.4) months. In five patients with tumor re-growth, four were salvaged by radical rectal resections and one received local excision. The distant metastasis rate was 5.7%(2/35), one patient presented resectable liver metastasis and received radical resection, another patient presented multiple bone metastases and was still alive. The median follow-up time was 43.7(6.1-71.4) months. At three years, the organ-preservation rate was 88.6%(31/35), the sphincter-preservation rate was 97.1% (34/35). No local recurrence was observed in five patients who received salvage surgery. The non-re-growth DFS was 94.0%. Three patients died of non-rectal cancer related events. The cancer-specific survival was 100%, the overall survival was 92.7% and the stoma-free survival rate was 90.0%. Organ preservation surgery or "watch and wait" strategy for cCR or near-cCR patients is feasible and achieves good outcomes. This strategy can be an alternative to standard care, improve patient's quality of life and facilitate tailored treatment for mid-low rectal cancer following nCRT, however, it should be cautiously applied in near-cCR patients before local excision biopsy.

To investigate the long-term outcome of organ preservation with local excision or "watch and wait" strategy for mid-low rectal cancer patients evaluated as clinical complete remission (cCR) or near-cCR following neoadjuvant chemoradiotherapy (NCRT). Clinical data of 62 mid-low rectal cancer patients evaluated as cCR/near-cCR after NCRT undergoing organ preservation surgery with local excision or receiving "watch and wait" strategy at Department of Gastrointestinal Surgery, Peking University Cancer Hospital and Institute from March 2011 to August 2017 were retrospectively analyzed. According to the approximate 1:2 pairing, 123 patients who underwent radical resection with complete pathological remission(ypCR) after neoadjuvant chemotherapy during the same period were selected for prognosis comparison. The primary endpoint of the study was 3-year non-regrowth disease-free survival (NR-DFS) and tumor specific survival (CSS). Survival analysis was performed using the Kaplan-Meier curve (Log-rank method). The secondary endpoint of the study was 3-year organ preservation and sphincter preservation. The retrospective study included 38 male and 24 female patients. The median age was 60 (31-79) years and the median distance from tumor to anal verge was 4(1-8) cm. The ratio of cCR and near-cCR was 79.0%(49/62) and 21.0%(13/62) respectively. Local regrowth rate was 24.2%(15/62). Of 15 with tumor regrowth, 9 patients received salvage radical rectal resection and no local recurrence was found during follow-up; 4 patients received salvage local excision among whom one patient had a local recurrence occurred patient; 2 patients refused further surgery. The overall metastasis rate was 8.1%(5/62), including resectable metastasis(4.8%,3/62) and unresectable metastasis (3.2%,2/62). The valid 3-year organ preservation rate and sphincter preservation rate were 85.5%(53/62) and 95.2%(59/62) respectively. The median follow-up was 36.2(8.6-89.0) months. The 3-year NR-DFS of patients with cCR and near-cCR was 88.6% and 83.1% respectively, which was not significantly different to that of patients with ypCR (94.7%, P=0.217). The 3-year CSS of patients with cCR and near-cCR was both 100%, which was not significantly different to that of patients with ypCR(93.4%, P=0.186). Mid-low rectal cancer patients with cCR or near-cCR after NCRT undergoing organ preservation with local excision or receiving "watch and wait" strategy have good long-term prognosis with low rates of local tumor regrowth and distant metastasis, which is similar to those with ypCR after radical surgery. This treatment mode may be used as an option for organ preservation in mid-low rectal cancer patients with good tumor remission after NCRT.

The aims of the treatment of penile and testicular cancer are complete tumor removal with as much organ preservation as possible, without compromising oncological control. Surgical treatment can be mutilating and devastating for the patient’s psychological well-being; however, organ preserving strategies must be weighted on the impact of cancer recurrence on long-term survival. Herein, we present epidemiology, clinical characteristics, and oncological outcomes of these urological cancer as well as andrological and functional consideration on organ preserving strategies for penile cancer, fertility, and sexual disfunction after treatment for testicular cancer.

The Current Role of Partial Surgery As a Strategy for Functional Preservation in Laryngeal Carcinoma

El papel actual de la cirugía parcial como estrategia de preservación funcional en el carcinoma de laringe

Penile cancer is a rare clinical entity that contributes to significant patient morbidity and mortality. Human papilloma virus (HPV) plays an important role in the carcinogenesis of penile squamous cell carcinoma (SCC), is associated with improved clinical outcomes, and is predictive for response to treatment with chemotherapy and radiotherapy. Historically, treatment consisted of radical surgery with partial or total penectomy. While effective for local control, surgical resection can impart significant physical, psychological and sexual dysfunction for afflicted men. Organ preservation strategies offer significant quality of life advantages over standard surgery and can be utilized without compromising oncological control. As an alternative or adjunct to surgical resection, radiation therapy can be used for organ preservation strategies successfully in up to 70% of patients. A variety of treatment techniques can be employed depending on the location and burden of disease. Limited disease can be amenable to treatment with interstitial brachytherapy, surface mold plesiotherapy or external beam radiotherapy. For locally advanced presentations, or for patients not amenable to surgical resection, excellent clinical outcomes can be achieved using a combination of chemotherapy and radiation therapy. Here, we discuss the management of penile SCC using modern radiation therapy treatment techniques, the expected clinical outcomes for organ preservation, as well as the management of side-effects and toxicities. While large randomized trials are being developed, the management of penile cancer is informed from the management of other of other anogenital malignancies, which we also review.

Multimodal treatment strategies for patients with rectal cancer are increasingly including the possibility of organ preservation, through nonoperative management or local excision. Organ preservation strategies can enable patients with a complete response or near-complete clinical responses after radiotherapy with or without concomitant chemotherapy to safely avoid the morbidities associated with radical surgery, and thus to maintain anorectal function and quality of life. However, standardization of the key outcome measures of organ preservation strategies is currently lacking; this includes a lack of consensus of the optimal definitions and selection of primary end points according to the trial phase and design; the optimal time points for response assessment; response-based decision-making; follow-up schedules; use of specific anorectal function tests; and quality of life and patient-reported outcomes. Thus, a consensus statement on outcome measures is necessary to ensure consistency and facilitate more accurate comparisons of data from ongoing and future trials. Here, we have convened an international group of experts with extensive experience in the management of patients with rectal cancer, including organ preservation approaches, and used a Delphi process to establish the first international consensus recommendations for key outcome measures of organ preservation, in an attempt to standardize the reporting of data from both trials and routine practice in this emerging area.

To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.