Impact of the COVID‐19 pandemic on urological cancers: The surgical experience of two cancer hubs in London and Milan

Abstract Objective To report on the outcomes of urological cancer patients undergoing radical surgery between March–September 2020 (compared with 2019) in the European Institute of Oncology (IEO) in Milan and the South East London Cancer Alliance (SELCA). Materials and Methods Since March 2020, both institutions implemented a COVID‐19 minimal ‘green’ pathway, whereby patients were required to isolate for 14 days prior to admission and report a negative COVID‐19 polymerase chain reaction (PCR) test within 3 days of surgery. COVID‐19 positive patients had surgery deferred until a negative swab. Surgical outcomes assessed were: American Society of Anaesthesiologists (ASA) grade; surgery time; theatre time; intensive care unit (ICU) stay >24 h; pneumonia; length of stay (LOS); re‐admission. Postoperative COVID‐19 infection rates and associated mortality were also recorded. Results At IEO, uro‐oncological surgery increased by 4%, as compared with the same period in 2019 (n = 515 vs. 534). The main increase was observed for renal (16%, n = 98 vs. 114), bladder (24%, n = 45 vs. 56) and testicular (27%, n = 26 vs. 33). Patient demographics were all comparable between 2019 and 2020. Only one bladder cancer patient developed COVID‐19, reporting mild/moderate disease. There was no COVID‐19 associated mortality. In the SELCA cohort, uro‐oncological surgery declined by 23% (n = 403 vs. 312) compared with the previous year. The biggest decrease was seen for prostate (−42%, n = 156 vs. 91), penile (−100%, n = 4 vs. 0) and testicular cancers (−46%, n = 35 vs. 24). Various patient demographic characteristics were notably different when comparing 2020 versus 2019. This likely reflects the clinical decision of deferring COVID‐19 vulnerable patients. One patient developed COVID‐19, with no COVID‐19 related mortality. Conclusion The COVID‐19 minimal ‘green’ pathways that were put in place have shown to be safe for uro‐oncological patients requiring radical surgery. There were limited complications, almost no peri‐operative COVID‐19 infection and no COVID‐19‐related mortality in either cohort.

being postponed on the assumption that COVID-19 infection was associated with higher postoperative morbidity and mortality. 6 An early international multicentre study looking at perioperative COVID- 19 infection reported a postoperative 30-day mortality of 24%, with a pulmonary complication rate of 50% in patients with perioperative COVID-19. 7 Routine outpatient clinics and elective surgery was cancelled to allocate resources, and only urgent and high-risk cancer surgery was performed. 4 Over a year into the COVID-19 pandemic, epidemiological evidence has now reported a significant decrease in urgent cancer referrals. 8 This has led to a delay in cancer diagnoses and treatment resulting in more cases of advanced disease at referral. 5 A recent cohort study reported that substantial increases in the number of cancer deaths in the UK are to be expected as a result of diagnostic delays due to  In this context, safe pathways and guidelines were developed to minimise the risk of contracting COVID-19 while balancing treatment options. 9 A similar recent study looking at overall surgical practice in cancer patients in the same two populations reported favourable outcomes when implementing these pathways. 10 The

| SELCA
A multidisciplinary team, formed by a panel of clinicians and a dedicated tumour board, assessed patients' risk profiles according to new UK government guidance in relation to their co-morbidities and the potential negative effects of COVID-19. If the health risks were deemed too high, patient care was directed to an alternative nonsurgical pathway. The need for a postoperative critical care unit (CCU) bed was evaluated and if deemed too high risk or prolonged stay was expected (i.e., performance status of >3), alternative treatments were considered. An enhanced consenting process was utilised, which included agreed levels of care in the postoperative period with some patients electing not to have CCU care if their condition deteriorated after surgery. All patients were instructed to self-isolate for 14 days to minimise the risk of acquiring COVID-19 infection in the perioperative period. Two negative swabs were required during surgical pre-assessment in order to proceed to surgery. If the staging computed tomography (CT) scan of the chest identified incidental COVID-19 disease, surgery would be delayed for at least 14 days, irrespective of whether patients had the required two negative swabs.
At the time of anaesthetic induction, all patients were intubated in the operating theatre with only the anaesthetic team within the operating theatre suite and wearing full PPE. Once the endotracheal tube was placed, a wait time of 20 min was mandatory before entering the theatre suite; this was to allow for adequate air exchanges to occur and minimise the exposure to any aerosol generated during intubation.
During surgery itself, only essential personnel were in the operating theatre and full PPE was worn by all theatre staff. There was no teaching or training in this period. All surgical procedures were consultant led and delivered to optimise procedural efficiency and utilisation of theatre time.
To optimise sterility of surgical wounds, povidone-iodine (Betadine) preparation was used for all surgery site cleaning and preparation. A smoke and gas insufflation and evacuation system (ConMed Airseal ® ) was used in all minimally invasive aerosol generating cases.
Intra-abdominal pressure was limited to 12 mmHg with lower insufflation pressures used as standard when possible. Robotic/laparoscopic ports were never vented to the atmosphere. A retrieval bag was chosen that could be placed through a sealed port. At the end of the procedure all gas was aspirated, via a filtered suction unit, from the least dependent port.
Once surgery was complete, the patient remained in the theatre for a further 20 min following extubation, prior to being transferred to the recovery room. Additionally, there was a mandatory simulation training programme for all theatre staff, which included putting on ('donning') and removing ('doffing') of PPE techniques, intubation techniques and failed intubation drills.
Full PPE used by all physicians in both Institutes comprised of: filtering face piece 2 (FFP2) mask, in addition to a surgical mask, water-repellent disposable gown, double gloves, and protective goggles or visor. In the surgical theatres the protocol was to have an area of donning and doffing in line with Public Health England (PHE) guidelines. 18,19 Lastly, health personnel were swabbed every 7 days to detect asymptomatic vectors. Figure 1B illustrates the pre-operative patient and staff COVID-19 protocols for SELCA. The data collection for SELCA was approved by and Guy's Cancer Cohort (Reference number: 18/NW/0297).  Tables 1 and S1. Age, sex, SES, ethnicity and comorbidities were all comparable between both periods (i.e., 90% male, 60% high SES and 37% with hypertension). Data on performance status were not available. Surgical outcomes of IEO patients are summarised in Table 3       Similarly, advanced renal cancers require a higher priority for timely  28,29 In addition, it has also been reported that neoadjuvant hormonal therapy does not negatively impact longterm survival and allows patients to safely delay surgery. 27 Moreover, the decline in the number of penile cancer surgery is also in line with published studies. It has been reported that topical treatment is effective and should be the first option in the absence of lymph node involvement, while radiotherapy has had good results in more advanced lesions. 30 As previously mentioned for testicular cancer, there is limited information on the effects of delaying surgical treatment due to COVID-19. However, a recent review reported that testicular cancer patients would benefit from minimised delays and their treatment should be prioritised. 27 There was a 300% increase in the number of adrenal surgeries (n = 1 vs. 4); this is likely due to the associated endocrine abnormalities from hormone secreting tumours and the need for early surgical treatment. 31,32 In both hubs, the decision making for the surgical prioritisation was individually reviewed by a virtual tumour board and treatment plans were personalised taking into account the patients' clinical characteristics. In the SELCA population, some patient characteristics were fairly different when comparing 2020 with 2019 (i.e., 61% vs. 82% male, 29% vs. 50% aged >70 years, 3% vs. 29% with hypertension), which likely reflects the clinical decision making for COVID-19 vulnerable patients. The risks and benefits of each procedure should be assiduously weighed against the potential risk of contracting COVID-19. 10 The deferral of cancer treatment has created a backlog of patients and this will likely have great implications for both patients and healthcare workers. Although we are aware that early reports suggest patients are at high risk of perioperative infection and subsequent high risk of mortality, there is increasing epidemiological evidence suggesting that the risk of COVID-19 infection is minimal with safety precautions. 9,20,27 Thus, it is critical for more cancer centres to begin to implement COVID-19 pathways and reintroduce elective cancer surgery to prevent more delays in oncological care.

| Statistical analyses
The current study is among the first large observational study looking at safe pathways for uro-oncological surgical procedures implemented in two cancer hubs, in Milan and South-East London.
Further studies are needed stratifying cancer subtypes and stages, as well as the types of surgical procedures performed to carry out an indepth review into the safest pathways for cancer patients. In addition, a more detailed description of the criteria used for prioritisation of cancer surgery is needed to further inform future clinical guidelines.
The major limitations of our study include the lack of data on: COVID-19 severity for SELCA patients, COVID-19 test results of healthcare staff in both centres, and COVID-19 test results in the postoperative period. Moreover, the differences in each cancer hub's COVID-19 'green' pathway may be a potential source for bias.

| CONCLUSIONS
The findings from our study suggest that the COVID-19 minimal 'green' pathways implemented in our study populations are safe for patients who require radical treatment for genitourinary malignancy.
Continuation of major surgery for urological cancer should be encouraged during the ongoing COVID-19 pandemic provided appropriately designed preventative pathways to avoid the spread of COVID-19 are implemented. Moreover, it is critical for all urological cancer centres to identify measures to manage the backlog of cancer patients awaiting treatment either through initial deferral or delayed referral.