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Editorial: PSMA PET/CT imaging for primary staging of intermediate and high-risk PCa

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In this month’s issue Yaxley et al. [1] describe a retrospective study of 68Ga-labelled prostate specific membrane antigen (68Ga-PSMA) positron emission tomography – computed tomography (PET/CT) in 1253 men at primary staging. The primary aim was to determine the risk of metastatic disease on 68Ga-PSMA PET/CT in risk categories including prostate specific antigen (PSA) level, ISUP grade and multiparametric magnetic resonance imaging (mpMRI) stage. The majority of patients had PSA < 10 ng/ml (78%) and / or T2 tumours (74%) with a relatively even distribution across ISUP grades from 1 to 5. Overall, metastases were detected in 12.1% of men and unsurprisingly, were more common in patients with high PSA >20ng/ml and/or ISUP 4-5 and/or T3b stage. Increasing PSA, ISUP grade and T-stage were all statistically significant prognostic factors on univariate and multivariate analysis. In men with at least one intermediate risk factor (T2, PSA 10-20 ng/ml, ISUP 2-3), 5.2% had metastases and in those with at least one high risk factor, 19.9% had PSMA-avid metastases.

On a sub-analysis of lymph node metastases (107 men), there was increased risk of nodal disease with increasing PSA, ISUP grade and T-stage. Of note, nearly 50% of lymph node metastases were outside an extended lymph node dissection field. Skeletal metastases, occurring in 59 men, were also more frequent in these higher risk groups. Interestingly, not all primary tumours (91.7%) were PSMA-avid (SUVmax > 3.0), consistent with previous estimations of less than 10% of prostate cancer not expressing PSMA significantly.

There is a large body of evidence supporting the use of 68Ga-PSMA PET/CT in biochemical recurrence of prostate cancer, with superior sensitivity over other PET tracers such as 18F-choline or 18F-fluciclovine, particularly at low PSA levels (1 and 2ng/ml, respectively) [2,3]. There is less evidence supporting the use of 68Ga-PSMA PET/CT in primary staging, although the literature that does exist is positive. In 130 patients with intermediate or high-risk disease, sensitivity and specificity for lymph node detection on a template-based analysis has been reported to be 68.3% and 99.1%, respectively, significantly better sensitivity than conventional morphological imaging (27.3% and 97.1%, respectively) [4]. Whilst, the negative predictive value might not be sufficiently high to avoid considering lymph node dissection in patients at increased risk of nodal metastases, there is nevertheless potential to substantially improve on conventional morphological imaging for nodal staging. In addition, there is evidence that 68Ga-PSMA PET/CT leads to changes in management in at least 21% of patients being staged with intermediate or high-risk disease [5]. The large retrospective cohort reported by Yaxley et al. [1] contributes to this growing evidence base and suggests that 68Ga-PSMA PET/CT has a place in staging high-risk, and probably intermediate risk, patients before definitive treatment. The retrospective nature allows potential referral bias but the data benefits from a large cohort in real-life current practice.

What this study does not tell us is the incremental benefit of 68Ga-PSMA PET/CT over conventional imaging with mpMRI, bone scan and CT scan. However, the prospectively recruiting proPSMA study will provide these data shortly [6]. Secondly, no histopathological or follow up reference standard was available in this study. However, 68Ga-PSMA PET/CT is known to be very specific with few false positive results and the authors adopted a relatively robust criterion for positivity (moderate or high uptake with a CT correlate) to minimise false positive results. However, some sensitivity may have been lost, e.g. mildly positive metastases or PSMA-positive but CT-negative bone lesions, a not infrequent occurrence in our experience. An additional practical detail is that contrast-enhanced CT was employed to aid differentiation of ureteric activity from abdominal and pelvic lymph nodes. This is not routine in all PET departments.

The results from the proPSMA study are eagerly awaited [6]. In the meantime, the imaging and clinical prostate community will also need to tackle the issues of having several 68Ga and 18F-labelled PSMA analogues available to choose from, with subtle differences in biodistribution, diagnostic accuracy and cost. There seems no doubt however, that PSMA-based PET imaging will continue to play a substantial part in the management of patients with prostate cancer at various points in their management pathway and that robust prospective evidence will continue to accumulate to a level that funders will not be able to ignore.

References

  1. Yaxley J, Raveenthiran S, Nouhaud FX, et al. Risk of metastatic disease on 68Ga-PSMA PET/CT scan for primary staging of 1253 men at the diagnosis of prostate cancer. BJU Int 2019; xx: xxx-xxx.
  2. Treglia G, Pereira Mestre R, Ferrari M, et al. Radiolabelled choline versus PSMA PET/CT in prostate cancer restaging: a meta-analysis. Am J Nucl Med Mol Imaging 2019; 9: 127-39.
  3. Calais J, Ceci F, Nguyen K, et al. Prospective head-to-head comparison of 18F-fluciclovine and 68Ga-PSMA-11 PET/CT for localization of prostate cancer biochemical recurrence after primary prostatectomy. J Clin Oncol 2019; 37: 7_suppl, 15-15.
  4. Maurer T, Gschwend JE, Rauscher I, et al. Diagnostic efficacy of (68)Gallium-PSMA positron emission tomography compared to conventional imaging for lymph node staging of 130 consecutive patients with intermediate to high risk prostate cancer. J Urol 2016; 195: 1436-43.
  5. Roach PJ, Francis R, Emmett L, et al. The Impact of (68)Ga-PSMA PET/CT on Management Intent in Prostate Cancer: Results of an Australian Prospective Multicenter Study. J Nucl Med 2018; 59: 82-8.
  6. Hofman MS, Murphy DG, Williams SG, et al. A prospective randomized multicentre study of the impact of gallium-68 prostate-specific membrane antigen (PSMA) PET/CT imaging for staging high-risk prostate cancer prior to curative-intent surgery or radiotherapy (proPSMA study): clinical trial protocol. BJU Int 2018; 122: 783-3.

 

Editorial: Reducing the rate of uretero‐enteric strictures after robot‐assisted cystectomy: a green light for immunofluorescence?

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In the current edition of the BJUI, Ahmadi et al. [1] from the University of Southern California describe their experience with the use of indocyanine green (ICG) during robot‐assisted radical cystectomy (RC); specifically, they discuss its potential utility in assessing the vascularity of distal ureteric segments ahead of anastomosis to the bowel segment during urinary diversion.

Benign postoperative ureteric strictures are thought to be largely attributable to inadequate vascularization of the distal ureter on account of its segmental blood supply. Despite meticulous dissection technique and avoidance of traction or anastamotic tension, many series still report a stricture rate in the order of 10% in both open and minimally invasive surgery. Conventionally, the left ureter is associated with a higher risk because of its more extensive mobilization and longer trajectory behind the recto‐sigmoid.

Notably, there were early indications in the 1990s that minimally invasive surgery had the potential to increase the risk of ureteric complications, and this was highlighted by various authors pioneering the introduction of laparoscopic live donor nephrectomy [2,3,4]. Surgeons at that time cited magnification as a potential culprit, with intra‐operative views suggesting a well‐preserved peri‐ureteric tissue bundle but an ex vivo ureter that appeared more denuded when examined with the ‘naked eye’.

In the present study, the theoretical construct applied was that the use of ICG could potentially remove the subjectivity of the surgeon’s assessment of distal ureteric vascularity and replace it with a more objective visual guide through the use of immunofluorescence after administration of ICG. The study design was an interrupted time series rather than a randomized trial, but was set in the context of a unit where all surgeons reported over a decade of experience each in performing robot‐assisted RC in a high‐volume setting.

Indocyanine green is a fluorescent, non‐toxic tracer that can be visualized with an infra‐red camera but remains non‐visible in conventional white light. It established its initial position within the robotic theatre by being popularized for the assessment of vascularity of renal tumours, particularly during nephron‐sparing surgery [5]. Once injected, there is an initial arterial phase followed by a later tissue perfusion phase where the tissue itself can be seen to fluoresce if vascularized adequately. The initial arterial phase is rapid (30 s), followed several minutes later by the perfusion phase.

After its introduction at the USC Institute of Urology, surgeons used the infra‐red findings of ICG administration to guide the length of distal ureteric resection in preparation for the uretero‐enteric anastomosis. Ureteric stricture rates were assessed at 12–14 months postoperatively based on clinical or radiological suspicion of stricturing. Confirmatory tests included a loopogram or cystogram and functional nuclear imaging. In some cases, nephrostomy and antegrade studies were performed.

The study found a marked reduction in stricture rate, from 10.6% in the non‐ICG group to an undetectable rate in the ICG group at this stage of follow‐up. This was associated with a greater length of resected ureteric segment in the ICG group compared to the non‐ICG group.

If viewed in the context of a single‐centre feasibility study, then the findings suggest a technique that is safe, is reproducible and has the potential to markedly reduce a challenging and not insignificant postoperative complication of RC. The findings would also support the authors’ theoretical construct that ischaemia and fibrosis are the key drivers of ureteric stricturing following RC.

It is of course acknowledged in the paper that further studies across multiple centres are needed for validation, but the findings so far would indicate that extending its further evaluation is warranted. It will also be of interest to see whether surgeons experienced in this technique would eventually develop the expertise to identify a poorly perfused ureter without the need for ICG based on pattern recognition and or greater confidence in excising longer ureteric segments.

References

  1. Ahmadi N, Ashrafi AN, Hartman N et al. Use of indocyanine green to minimise uretero‐enteric strictures after robotic radical cystectomy. BJU Int 2019; 124: 302– 7
  2. Ratner LE, Cisek LJ, Moore RG, Cigarroa FG, Kaufman HS, Kavoussi LR. Laparoscopic live donor nephrectomy. Transplantation 1995; 60: 1047– 9
  3. Philosophe B, Kuo PC, Schweitzer EJ et al. Laparoscopic vs open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique. Transplantation 1999; 68: 497– 502
  4. Kavoussi LR. Laparoscopic donor nephrectomy. Kidney Int 2000; 57: 2175– 86
  5. Tobis S, Knopf JK, Silvers CR et al. Near infrared fluorescence imaging after intravenous indocyanine green: initial clinical experience with open partial nephrectomy for renal cortical tumors. Urology 2012; 79: 958– 64

 

Editorial: A new horizon for bladder preservation in muscle‐invasive bladder cancer

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We are witnessing a shift toward treatment de‐escalation in muscle‐invasive bladder cancer. Patients diagnosed with muscle‐invasive bladder cancer have traditionally faced two treatment options: (1) radical cystectomy with urinary diversion or (2) chemoradiation, both of which can impact quality of life and subsequent morbidity while variably influencing recurrence rates. Recent research has turned toward treatment de‐escalation in an attempt to preserve the bladder while maintaining survival rates. In this issue of BJUI, Kijima et al. [1] propose a tetramodal treatment regimen which combines chemoradiation with partial cystectomy, in an attempt to avoid radical cystectomy without compromising recurrence and survival. Similar ongoing clinical trials are beginning to explore the role of treatment de‐escalation by potentially avoiding cystectomy and/or radiation altogether. Dr Daniel Geynisman is leading a phase II trial at Fox Chase Medical Centre to investigate the role of single‐modality chemotherapy [2]. In that study, therapy is individualized by applying a risk‐adapted approach to identify genetic mutations in cancer cells to predict whether chemotherapy will be effective in eliminating all cancer and preventing future recurrence and metastasis. A related study led by Dr Alexander Kutikov is assessing the reliability of cystoscopic evaluation in predicting pT0 urothelial carcinoma of the bladder at the time of radical cystectomy [3]. By identifying urine biomarkers, investigators could potentially identify those patients who will respond completely to neoadjuvant chemotherapy, thus obviating the need for subsequent cystectomy.

While these studies have not yet provided definitive evidence to forgo definitive therapy (whether it be chemoradiotherapy or radical cystectomy), in this issue of BJUI, Kijima et al. [1] propose similar de‐escalation efforts to promote bladder preservation in a carefully selected population, by preserving quality of life with chemoradiation while addressing the potential increased risk of recurrence with partial cystectomy. The authors report the oncological and functional outcomes of a series of patients who underwent a new tetramodal bladder preservation treatment combination for muscle‐invasive bladder cancer [1]. After patients underwent maximal transurethral bladder tumour resection, induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection, only 4% of patients experienced recurrence of muscle‐invasive bladder cancer over a median follow‐up of 2 years, with an overall cancer recurrence rate of 18% and a 5‐year cancer‐specific survival of 93%.

When comparing these findings with the bladder cancer recurrence rates after partial cystectomy in the setting of muscle‐invasive disease (~40%) [4] and trimodal bladder preservation therapy (11–19%) [5], the findings presented in this paper are remarkable. Although the lower recurrence rate observed in this patient series may be influenced by a shorter follow‐up time than other studies looking at similar outcomes in patients treated for muscle‐invasive bladder cancer, the results of this paper demonstrate a promising frontier in bladder cancer treatment, combining the benefits of trimodal therapy with the extirpative intent of surgery while preserving the bladder. The long‐term (>5 year) cancer‐specific outcomes of these patients, however, remain unknown and are important to examine in order to contribute to our understanding of the true efficacy of this bladder cancer management strategy.

Given that treatment de‐escalation and bladder preservation share the goal of reduced morbidity and improved quality of life, functional outcomes after tetramodal therapy remain unclear yet critical. Differences in functional outcomes between cystectomy and bladder preservation also remain unclear, as randomized trials in this space are challenging to accrue, a lesson learned with the SPARE trial [6, 7]. Certainly, radiation and partial cystectomy are interventions that can decrease bladder capacity and result in irritative LUTS. The extent to which tetramodal therapy impacts these functional outcomes will be important to address moving forward. Despite the absence of a pre‐treatment baseline symptom profile, the overall favourable urinary quality‐of‐life score and reasonable bladder capacity after treatment completion are encouraging and suggest adequate patient tolerability.

As we usher in a new era of personalized medicine in muscle‐invasive bladder cancer, tetramodal bladder preservation treatment may have a role in bladder preservation by decreasing recurrence while maintaining quality of life. We look forward to long‐term data regarding oncological and functional outcomes to determine if this treatment strategy offers a significant benefit when compared with the ‘gold standard’ therapies for muscle‐invasive bladder cancer.

by Pauline Filippou and Angela B Smith

References

  1. Kijima T, Tanaka H, Koga F et al. Selective tetramodal bladder‐preservation therapy, incorporating induction chemoradiotherapy and consolidative partial cystectomy with pelvic lymph node dissection for muscle‐invasive bladder cancer: oncological and functional outcomes of 107 patients. BJU Int 2019; 124: 242– 50
  2. Phase II Trial of Risk Enabled Therapy after Initiating Neoajduvant Chemotherapy for Bladder Cancer (RETAIN BLADDER), 2018. Available at: https://www.carislifesciences.com/wp-content/uploads/2018/02/ASCO-GU-A-Phase-II-Trial-of-Risk-Enabled-Therapy-After-Initiating-Neoadjuvant-Chemotherapy-for-Bladder-Cancer-RETAIN-BLADDER.pdf. Accessed April 2019
  3. Cystoscopic Evaluation Predicting pT0 Urothelial Carcinoma of the Bladder, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT02968732. Accessed April 2019
  4. Fahmy N, Aprikian A, Tanguay S et al. Practice patterns and recurrence after partial cystectomy for bladder cancer. World J Urol 2010; 28: 419– 23
  5. Ploussard G, Daneshmand S, Efstathiou JA et al. Critical analysis of bladder sparing with trimodal therapy in muscle‐invasive bladder cancer: a systematic review. Eur Urol 2014; 66: 120– 37
  6. Huddart RA, Birtle A, Maynard L et al. Clinical and patient‐reported outcomes of SPARE ‐ a randomised feasibility study of selective bladder preservation versus radical cystectomy. BJU Int2017; 120: 639– 50
  7. Huddart RA, Hall E, Lewis R, Birtle A, Group STM. Life and death of spare (selective bladder preservation against radical excision): reflections on why the spare trial closed. BJU Int 2010; 106:753– 5

 

Editorial: The pursuit of purpose: reframing strategies to prevent physician burnout

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If there is one virtue that drives surgery residents to toil away in sterile, brightly lit operating rooms for extended hours for the best years of their life, it is the pursuit of purpose. However, these extended hours can also lead to what the WHO has now officially recognized as a medical condition: burnout. In a study in this issue of BJUI, Marchalik et al. [1] use qualitative analysis to elaborate on the prevalence and predictors of burnout among urology residents in the USA and in four European countries. Using an anonymous survey, the authors report a high prevalence of burnout in urology residents in both cohorts, with the European residents (44%) experiencing a higher burden than their US counterparts (38%). Given the recent focus, in the academic as well as general media, on the importance and severe implications of physician burnout, and the recognition of burnout as a disease by WHO, the timing of this publication for concrete organizational action seems propitious, especially since this analysis combines data from two continents with different institutional and educational frameworks, providing more granular data for a particularly immersive surgical specialty with a high rate of burnout.

Most recently, a cost–consequence analysis reported that physician burnout costs approximately $4.6 bn each year to the US healthcare system, with a cost of $7600 per‐physician‐per‐year at the institutional level resulting from reduced clinical productivity and turnover [2]. While addressing these economic losses from burnout is important from an organizational and health system point of view, focusing on these alone would be missing the larger picture. It is only when we consider the depersonalization, emotional drainage, and loss of professional and personal accomplishment associated with burnout that we begin to realize the scope of this epidemic. Deservedly, burnout is being recognized as a ‘moral injury’ [3]. And indeed, it is a moral injury: when physicians working under systems that betray their purpose as a healer, the damage is not only professional and systematic, but deeply personal as well.

The constant act of balancing competing demands – the financial interests of the healthcare institutions, looming litigations and ever‐changing documentation requirements – has undermined effective human interactions with patients and diminished the zeal that drives physicians to spend a major part of their youth in training. Journalist Diane Silver defines moral injury as ‘a deep soul wound that pierces a person’s identity, sense of morality, and relationship to society’ [3]. Except in the context of healthcare delivery, this injury extends to deterioration of relationships with patients and fellow physicians. Indeed, burnout among physicians has been demonstrated to be associated with suboptimal patient care [4], and the consequent inability to deliver high‐quality care because of health system deficiencies leads to decline in physician well‐being and professional dissatisfaction [5].

While the urgency of addressing physician burnout is obvious, this study by Marchalik et al. is also valuable as it highlights some of the practices that are protective, revealing lessons that can be implemented. The authors report that burnout was significantly lower among residents who sought mental health services and those who had access to structured mentorship. Unsurprisingly, those who had a caring environment experienced less depersonalization and emotional drainage. This is an instructive lesson for the residency programme directors: if they want their most important human resource to flourish, they need to start building supportive work environments. This could start with pairing interns and residents with dedicated and experienced faculty mentors; these initiatives would facilitate career coaching and provide space where residents feel comfortable seeking information on mental healthcare.

Interestingly, the authors also found a significant dose–response relationship between the number of non‐medical books residents read per month and decreased rates of burnout. This finding may surprise some healthcare administrators, who have routinely attempted to integrate ‘wellness’ and ‘mindfulness’ into clinical programmes to stimulate physician motivation, without much benefit. However, the positive relationship between non‐medical literature and medicine is an ancient one. Fortunately, in the last few decades, this relationship has witnessed a comeback and an increasing number of trainees are finding solace in their engagement with medical humanities and narrative medicine. These engagements have led to physicians developing emotional intelligence, empathy for patients and colleagues, and an opportunity to examine their role as healers [6]. This insight from the study should be another lesson for medical educators, who can encourage inclusion of reflections on life as a physician.

The epidemic of burnout among surgery residents requires immediate attention. Taking proactive action towards this is not only a matter of preventing economic loss or improving physician productivity, but an urgent ethical issue. All stakeholders – hospital administrators, healthcare policy‐makers, and regional physician leaders – must work together in developing inventive solutions to address the burnout epidemic. This will be essential to realizing the maximal potential of residency and reinstating purpose of clinical work.

References

  1. Marchalik, D, Goldman, CC, Carvalho, FFL et al. Resident burnout in USA and European urology residents: an international concern. BJU Int 2019; 124: 349‐ 56
  2. Han, S, Shanafelt, TD, Sinsky, CA et al. Estimating the attributable cost of physician burnout in the United States cost of physician burnout. Ann Intern Med 2019; 170: 784‐ 90
  3. Dean, W, Talbot, S. Physicians aren’t ‘burning out.’ They’re suffering from moral injury. STAT News 2018. Available at: https://www.statnews.com/2018/07/26/physicians-not-burning-out-they-are-suffering-moral-injury/. Accessed May 29, 2019.
  4. Shanafelt, TD, Bradley, KA, Wipf, JE, Back, AL. Burnout and self‐reported patient care in an internal medicine residency program. Ann Intern Med 2002; 136: 358– 67
  5. Friedberg, MW, Chen, PG, Busum, KR et al. Factors affecting physician professional satisfaction and their implications for patient care, health systems, and health policy. Rand Health Q 2014; 3: 1
  6. Bonebakker, V. Literature & medicine: humanities at the heart of health care: a hospital‐based reading and discussion program developed by the Maine humanities council. Acad Med 2003; 78:963– 7

 

Editorial: Dropping the GAD – just a fad?

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It is not without irony that, at the very moment that the UK’s National Institute for Health and Care Excellence (NICE) is poised to ratify the recommendation that multiparametric MRI (mpMRI) be introduced into the prostate cancer diagnostic pathway, we are seeking to significantly modify the very intervention on which they are about to provide judgement on [1].

The modification proposed is both compelling and plausible, as it renders the process of imaging the prostate in order to detect and localise clinically significant prostate cancer; simpler, quicker, safer and cheaper. It entails dropping the most complex and time‐consuming component of the three multiparametric sequences, the dynamic (time‐dependent) T1‐weighted gadolinium‐enhanced (GAD) sequence. This was a sequence that was, in the early days of MRI, imbued to have biological significance because it was capable of exploiting the differences in the microvascular architecture and function that we have tended to associate with cancer and non‐cancer in order to discriminate between the two. Or so we thought [2].

The systematic review in this issue of the BJUI by Alabousi et al. [3] explores, via the process of systematic review, whether the omission of the T1‐GAD sequence results in any clinically important reduction in test performance when compared with the full sequence scan comprising traditionally of T2, diffusion and T1‐GAD sequences. It did not.

By any stretch this is a tough analysis to pull‐off, as T1‐GAD sequences are not standardised in terms of acquisition or reporting. Every group seems to manage the dynamic images in a different way. As such they tend to suffer from quality control issues, possibly to a greater extent than the T2 and diffusion sequences. The verification of the signal by biopsy strategy and sampling intensity will have varied across studies, as will the threshold of the definition of clinically significant prostate cancer. These inherent methodological problems are all familiar to readers and issues that are pertinent to any imaging study in the detection of prostate cancer. However, there are two issues that make any current assessment of GAD vs no GAD really problematic. The first is the almost exclusive reliance on single‐centre retrospective data. In the few studies that claim a prospective design no comparative data were available. Studies of this type are typical in the early phase of exploring a clinical question and will, in time, be corrected. The other, largely hidden, hardly discussed and truly problematic issue relates to the manner by which we synthesise an overall risk score from the MRI sequences that we derive. The near ubiquitous use of the Prostate Imaging‐Reporting and Data System (PI‐RADS) scoring system introduces a systematic bias by the manner in which a Boolean form of logic is used to decide on the degree of influence that each sequence has in relation to the overall score. According to the manner by which PI‐RADS is applied, it tends to render the T1‐GAD sequence subordinate (only relevant in a minority of cases), contingent (to T2/diffusion) and disparate (dependent on prostate zone) in the way it is invoked [4]. The result is, that within the PIRADS framework, the T1‐GAD sequence is destined to play a relatively small role in driving the overall summary score of risk. It might, therefore, not be too surprising if its removal made little difference to the overall detection of clinically significant prostate cancer.

So what are the next steps? Clearly this is a very important issue and a simpler, quicker, safer and cheaper MRI would be desirable from multiple perspectives. It would render what is currently a complex intervention that comprises an invasive component into a totally passive image acquisition in which no medically trained health professional need be present. It is almost certainly a pre‐requisite for adoption in resource-poor jurisdictions and for entertaining the role of MRI as a primary population‐based screening test.

It took a large number of randomised trials to get mpMRI accepted into the prostate cancer diagnostic pathway. What is the minimum amount of evidence required to disinvest in one of its key components? In other words how many clinically significant cancers would we tolerate missing in order to offer the less complex test?

A direct (head‐to‐head) non‐inferiority randomised comparative study would, following some of our own recent calculations, require >3000 men to participate, which might just prove a little too challenging. An alternative approach is a study in which men would have lesions declared using a Likert score, thereby making no prior assumptions on the role and utility of any single sequence, by traditional mpMRI (standard) but also by a T2‐diffusion MRI (experimental) with appropriate blinding. Some lesions would be private to either standard or experimental imaging but most, it is likely, would be shared. All would require sampling. The yield, the misses, the test accuracy for each approach, could be calculated with necessary adjustments for the inevitable incorporation and verification biases.

It is interesting to observe that in many parts of the world mpMRI was introduced by clinicians before a large body of evidence was accumulated because they felt it was the right thing to do [5]. It may well be the case that ‘dropping the GAD’ will be subject to the same decision‐making process and precede any definitive judgement based on reliable evidence. Recent activity on PubMed would suggest that this might already have happened [6].

References

  1. National Institute for Health and Care Excellence (NICE). Non‐invasive MRI scan for Prostate Cancer recommended by NICE. Available at: https://www.nice.org.uk/news/article/non-invasive-mri-scan-for-prostate-cancer-recommended-by-nice. Accessed May 2019.
  2. Little, RA, Barjat, H, Hare, JI et al. Evaluation of dynamic contrast‐enhanced MRI biomarkers for stratified cancer medicine: how do permeability and perfusion vary between human tumours? Magn Reson Imaging 2018; 46: 98– 105
  3. Alabousi, M, Salameh, JP, Gusenbauer, K et al. Biparametric vs multiparametric prostate magnetic resonance imaging for the detection of prostate cancer in treatment‐naïve patients: a diagnostic test accuracy systematic review and meta‐analysis. BJU Int 2019; 124: 209– 20
  4. Turkbey, B, Rosenkrantz, AB, Haider, MA et al. Prostate Imaging reporting and Data System version 2.1: 2019 update of Prostate Imaging Reporting and Data System version 2. Eur Urol 2019 [Epub ahead of print]. https://doi.org/10.1016/j.eururo.2019.02.033
  5. Ahmed, HU, Kirkham, A, Arya, M et al. Is it time to consider a role for MRI before prostate biopsy? Nat Rev Clin Oncol 2009; 6: 197– 20
  6. Xu, M, Fang, M, Zou, J et al. Using biparametric MRI radiomics signature to differentiate between benign and malignant prostate lesions. Eur J Radiol 2019; 114: 38– 44

 

Editorial: Transcriptomic signatures for tertiary pattern 5 in prostate cancer

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Significant evidence is now emerging and publications have shown that the molecular characterization of tumours represents an important approach to stratifying patients with prostate cancer into appropriate treatments and their responses, helping to inform the next steps in the care pathway of these patients [1]. Understanding the functional role of the genes included in these signatures also gives an insight into the biology of the disease and how it develops and progresses.

BJUI has published papers in the past describing gene signatures that are associated with pathological Gleason score as pathological markers of aggressiveness and their potential role in predicting outcome [2].

The paper by Martini et al. [3] in the current issue of BJUI adds to this important literature. In a cohort of 159 patients, of whom 52 had tertiary pattern 5 (TP5) prostate cancer, Martini et al. showed that TP5 was associated with higher risk categories in the Decipher genomic score. Their study supports the literature showing that patients with TP5 have an elevated likelihood of developing disease after radical prostatectomy and have a poor prognosis [4]. It should be noted, however, that this is a small cohort with few patients defined as having TP5 disease. As prostate cancer is highly heterogeneous and gene expression can also be affected by the patient’s background, additional validation of this finding will be required in independent cohorts.

Additional analysis of the 698 gene by Martini et al. [3] identified a unique RNA signature of 18 genes for the TP5 cohort. A limitation of using the 698 gene previously demonstrated to be related to prostate cancer is that those with TP5 disease may be a unique subset of patients that may be associated with unfamiliar pathological pathways and new genes. An examination of novel genes whose expression pattern is unique to patients with TP5 disease may reveal additional genes.

Martini et al. then used the independent TCGA provisional database to link the expression of these 18 genes with clinical features. Patients harbouring any of the three genes CDKN2B, PLK1 and CDC20 mRNA were found to have worse progression‐free survival. The authors go on to undertake analysis of the 18 genes using the ingenuity network analysis tool identifying pathways involved in the cell cycle, DNA replication and repair, cellular assembly, cell death and survival and gene expression, which would fit with the biology of progressive disease. They also revealed a role in the dedifferentiation process and progression of cells towards anaplasia. They specifically identified CDKN2B, which has previously been associated with tumour suppression but might actually be linked to tumour progression, and identified it for further investigation.

Finally the researchers found that 13 genes out of the 18‐gene TP5 signature are upregulated in tumour lesions with TP5. Following these results they performed a sensitivity analysis in which the expression values of the genes in the cohort with GGG3‐4 and TP5 were compared with those of patients with GGG5 and discovered that these genes were similarly overexpressed in both groups. This finding strengthens the hypothesis that these genes are implicated in the dedifferentiation process of tumour cells, but it also raises the question of whether the pattern of expression of these genes is unique to patients with TP5 only, or whether it is associated with every tumour (primary, secondary or tertiary) that is classified as GGG5. Further research is needed to understand what the clinical significance of this genetic signature is and what pathological process it describes in practice.

This investigation into the functional role of the genes has given an insight into the biology of prostate cancer progression and TP5 disease which might inform a future area of research for novel biomarker panels and therapeutic interventions.

by R. William Watson and Omri Taltsh

References

  1. Cucchiara, V, Cooperberg, MR, Dall’Era, M, Lin, DW, Montorsi, F, Schalken, JA, Evans, CP Genomic markers in prostate cancer decision making. Euro Urol 2018; 73: 572– 82
  2. Pellegrini, K, Sanda, MG, Patil, D, Long, Q, Santiago‐Jiménez, M, Takhar, M, Erho, N, Yousefi, K,Davicioni, E, Klein, EA, Jenkins, RB, Karnes, RJ, Moreno, CS Evaluation of a 24‐Gene signature for prognosis of metastatic events and prostate cancer‐specific mortality. BJU Int 2017; 119: 961– 7
  3. Martini, A, Wang, J, Brown, NM, Cumarasamy, S, Sfakianos, JP, Rastinehad, AR, Haines, KG,Wiklund, NP, Nair, SS, Tewari, AK A transcriptomic signature of tertiary Gleason 5 predicts worse clinicopathological outcome. BJU Int 2019; 124: 155– 62
  4. Whittemore, DE, Hick, EJ, Carter, MR, Moul, JW, Miranda‐Sousa, AJ, Sexton, WJ Significance of tertiary Gleason pattern 5 in Gleason score 7 radical prostatectomy specimens. J Urol 2008; 179:516– 22

 

 

Editorial: Preoperative PSMA‐targeted PET imaging: more than just a tool for prostate cancer staging?

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The presence of lymph node metastases at the time of prostate cancer diagnosis has significant implications for treatment. According to current guidelines from the National Comprehensive Cancer Network, men with positive lymph nodes on initial staging imaging should be offered treatment with androgen deprivation (± abiraterone) along with consideration for external beam radiation therapy [1]. In contrast, men with clinically localised high‐ or very‐high‐risk prostate cancer have the option of undergoing radical prostatectomy. Unfortunately, currently available diagnostic imaging modalities (i.e. contrast‐enhanced CT and MRI) fall short in their ability to accurately identify lymph node metastases, which are often small and difficult to discern from other structures within the pelvis. Thus, there exists a conundrum: if we cannot accurately detect lymph node involvement, how can we appropriately manage it?

In this edition of the BJUI, Leeuwen et al. [2] report on the utility of molecular imaging with 68Ga‐PSMA‐11 positron emission tomography (PET)/CT in the preoperative staging of men with prostate cancer. To date, the greatest clinical utility of PSMA‐targeted PET has been in the management of men with biochemically recurrent prostate cancer [3]. In the present study by Leeuwen et al. [2], 140 patients with newly diagnosed intermediate‐ or high‐ risk prostate cancer underwent 68Ga‐PSMA‐11 PET/CT before radical prostatectomy with extended pelvic lymph node dissection. Surgical pathology served as the reference standard to which findings on 68Ga‐PSMA‐11 PET/CT were compared. In total, 27.1% of men were found to have radiotracer uptake in their pelvic lymph nodes, resulting in a sensitivity of 53% and a specificity of 88%. In contrast, multiparametric MRI had a sensitivity of only 14%, albeit with a higher specificity of 99%. These findings are in line with prior studies evaluating the diagnostic performance of PSMA‐targeted PET imaging for preoperative prostate cancer staging [4]. Of greater interest, however, is the authors’ observation that positivity on 68Ga‐PSMA‐11 PET/CT was strongly associated with postoperative PSA persistence (i.e. failure to cure). More specifically, after controlling for Gleason score, surgical margin status, and preoperative PSA level, positivity on PET/CT had an odds ratio of 5.87 (95% CI 1.30–26.59) for biochemical persistence. Furthermore, men with pN1 disease and a positive preoperative PET/CT (i.e. true positives) were over three times more likely to experience biochemical persistence than patients with pN1 disease and negative imaging (71.4% vs 21.4%). Thus, PSMA‐targeted PET not only stands to inform clinical staging, but also has the potential to offer independent prognostic information.

A future line of investigation is to explore the biological basis of the authors’ observation regarding PSMA as a prognostic marker. One explanation is that PET/CT identified men with higher volume lymph node metastases (a known prognostic factor), whilst patients with smaller more curable nodes were negative on imaging. After all, the authors state that the imaging test did not detect any pathologically positive lymph nodes <2 mm. Furthermore, only 27% of positive lymph nodes between 2 and 4 mm showed radiotracer uptake. Unfortunately, the authors did not account for differences in the volume of nodal metastases in their analysis. A second possible explanation for the authors’ observation is that PSMA is upregulated through the same signaling pathways that drive an aggressive prostate cancer phenotype, allowing for PSMA expression to provide prognostic information independent of tumour volume. Indeed, others have previously shown that PSMA expression, as measured by immunohistochemistry, corresponds with increasing tumour grade, stage and risk of biochemical failure [5]. Of course, these concepts are not mutually exclusive and further investigation is needed in order for PSMA‐targeted imaging to be rationally applied as a prognostic test.

References

  1. NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer (Version 4.2018). 2018. Accessed November 2018. Available at: https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf.
  2. Leeuwen, PJ, Donswijk, M, Nandurkar, R et al. Gallium‐68‐prostate‐specific membrane antigen (68Ga‐PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate‐ and high‐risk prostate cancer. BJU Int 2019; 124: 62– 8
  3. Han, S, Woo, S, Kim, YJ, Suh, CH. Impact of 68Ga‐PSMA PET on the management of patients with prostate cancer: a systematic review and meta‐analysis. Eur Urol 2018; 74: 179– 90
  4. Gorin, MA, Rowe, SP, Patel, HD et al. Prostate specific membrane antigen targeted 18F‐DCFPyL positron emission tomography/computerized tomography for the preoperative staging of high risk prostate cancer: results of a prospective, phase II, single center study. J Urol 2018; 199: 126– 32
  5. Minner, S, Wittmer, C, Graefen, M et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate 2011; 71: 281– 8

 

Editorial: Radical cystectomy complications and perioperative mortality

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Bladder cancer is the second most prevalent urological cancer, with 25% of cases being muscle invasive, which requires radical therapy as per National Institute for Health and Care Excellence (NICE) guidance [1]. Radical therapy often involves radical cystectomy (RC), which is an incredibly complex operation with common postoperative complications and significant mortality rates [1,2]. It is suspected to have a 30‐day mortality of between 1% and 3%, with this increasing to 10% in the >80 years age group [2, 3], and a 90‐day postoperative complication rate of 50–60% [4].

This complex procedure and its complication rates contribute to a myriad of factors that result in bladder cancer being the most expensive cancer, per patient, to care for and to treat [2, 4]. We congratulate the authors on producing this substantial paper investigating how postoperative complications are associated with overall mortality [5]. Logic dictates that the more complications a patient experiences, the worse the postoperative outcome and, ultimately, the higher the risk of mortality. This paper has succeeded in providing quantifiable data, not only on the overall correlation but by providing adjusted odds ratios (ORs) based upon the nature of the complication.

Whilst a 90‐day prospective study would have been ideal, we recognise this would have been much harder to perform and would have resulted in a much smaller cohort. This retrospective study will therefore suffer from selection bias and unmeasured confounders, as the authors have identified. It should also be noted that these results may not extrapolate to a global population due to data only being collected from a private healthcare system. The coding of clinical diagnosis is often overestimated due to funding that comes with diagnosis and treatments. Despite these biases, this is still the largest set of data investigating the association of RC complications and mortality.

The analysis of the data found that there was a ‘threshold’ limit for the number of complications postoperative patients could experience; patients experiencing four or more complications had a drastic increase in mortality (OR 76.6, P < 0.05) [5]. While all postoperative patients have close monitoring and enhanced recovery pathways, and any patients with postoperative complications will be repeatedly assessed, in an ideal world, patients who have experienced three or more complications would have increased monitoring (high dependency unit/intensive therapy unit).

The breakdown of complications by physiological system was unsurprising, with pulmonary (OR 6.5, P < 0.001), cardiac (OR 4.4, P < 0.001), and renal (OR 2.6, P < 0.001) complications being most associated with increased mortality [5]. Although this information does provide some guidance into specific monitoring methods for high‐risk patients, such as capnography, continuous blood pressure, and renal function monitoring.

While additional demographic and operational information was gathered, the only information collected pertaining to medical health was the Charlson Comorbidity Index (CCI), which meant the authors were unable to ascertain any correlation between the nature of the complications experienced and any predisposing condition of that physiological system. Schulz et al. [6] have recently published a report examining RC morbidity and mortality rates in relation to American Society of Anesthesiologists (ASA) grading and found that patients with an ASA score ≥3 had significantly more high‐grade complications, required more perioperative interventions, and had a higher mortality rate (7.6% vs 3.2%; P = 0.002). Mossanen et al. [5], have taken some of these factors into consideration using the CCI, but unfortunately ASA grade was not part of the data collected.

Due to the nature of the database collection method, the authors were unable to determine other important confounders such as smoking status, exercise tolerance, and the severity/specific details of the complications experienced. Sathianathen et al. [7] showed in October 2018, that smokers were almost twice as likely to have Clavien–Dindo III–V complications following RC, with the most common complications being pneumonia, myocardial infarction, and wound dehiscence.

In our view, Mossanen et al. [5] have provided the urological community with not only quantifiable evidence to support the maxim of ‘more complication, worse outcome’ but they have also identified a vital threshold that can be used clinically to support postoperative patients. This guidance, when paired with clinical judgement, could result in additional monitoring and multi‐disciplinary care in high‐risk patients, ultimately reducing RC mortality rates.

by Alex Hampson, Amy Vincent, Prokar Dasgupta and Nikhil Vasdev

References

  1. National Institute for Health and Care Excellence (NICE). Bladder cancer: diagnosis and management. NICE guideline NG2, February 2015. Available at: https://www.nice.org.uk/guidance/ng2. Accessed September 2018
  2. Shabsigh, A, Korets, R, Vora, KC et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55: 164– 76
  3. Froehner, M, Brausi, MA, Herr, HW, Muto, G, Studer, UE. Complications following radical cystectomy for bladder cancer in the elderly. Eur Urol 2009; 56: 443– 54
  4. Stitzenberg, KB, Chang, Y, Smith, AB, Nielsen, ME. Exploring the burden of inpatient readmissions after major cancer surgery. J Clin Oncol 2015; 33: 455– 64
  5. Mossanen, M, Krasnow, RE, Zlatev, DV et al. Examining the relationship between complications and perioperative mortality following radical cystectomy: a population‐based analysis. BJU Int2019; 124: 40– 6
  6. Schulz, GB, Grimm, T, Buchner, A et al. Surgical high‐risk patients with ASA ≥ 3 undergoing radical cystectomy: morbidity, mortality, and predictors for major complications in a high‐volume tertiary center. Clin Genitourin Cancer 2018; 16: e1141– 9
  7. Sathianathen, NJ, Weight, CJ, Jarosek, SL, Konety, BR. Increased surgical complications in smokers undergoing radical cystectomy. Bladder Cancer 2018; 4: 403– 9

 

Editorial: NICE guidelines on prostate cancer 2019

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The much‐anticipated National Institute for Health and Care Excellence (NICE) Guidelines are finally published [1] after a period of consultation when they were in the draft phase. These are updated from the previous 2008 and 2014 versions and reflect the changes in our knowledge and practice over the last 10 years. While there are many similarities, the astute reader will find distinct differences from the AUA Guidelines, which feature in a summary booklet released at the #AUA19 meeting in Chicago this spring.

NICE does not comment on screening for prostate cancer so many of us continue to rely on our Guideline of Guidelines [2], which make pragmatic recommendations such as smart screening in well‐informed men who are at higher risk because of their family history. For staging, bone scan has not been replaced by prostate‐specific membrane antigen (PSMA)‐positron‐emission tomography/CT, and Lu‐PSMA theranostics is yet to become an option in castrate‐resistant disease as the international trials are not mature.

Multiparametric MRI before prostate biopsy in men suitable for radical treatment is a new addition, based on the PROMIS [3] and PRECISION trials [1]. This approach is thought to be cost‐effective through reducing the number of biopsies and side effects despite the initial added cost of MRI scanning. In Grade Group 1 and some low‐volume Grade Group 2 cancers, protocol‐based active surveillance is recommended provided the patients are well counselled and it has been discussed by a multidisciplinary team.

To reduce variations in active surveillance, Prostate Cancer UK has carefully examined eight different guidelines and published a consensus statement for the benefit of our patients [4]. We have already promoted this widely on social media and hope that our readers will use this practical tool in their clinics. We often find that some patients just cannot live with a cancer inside their body and seek surgery as a result, however small their tumour. Careful discussion about management options and their risks vs benefits [1] can help patients arrive at a pragmatic decision. The effect of a cancer diagnosis on patients’ minds should therefore not be underestimated and a trained psychologist should be available for appropriate counselling.

NICE also recommends hypofractionated intensity‐modulated radiotherapy, if appropriate, in combination with androgen deprivation therapy (ADT) for localized disease, and methods of decreasing the side effects while increasing accuracy of radiation. As in 2014, robot‐assisted radical prostatectomy remains a surgical option in centres performing at least 150 of these procedures per year [1]. These numbers are similar to those published from other health services such as Canada. One such very high‐volume centre is the Martini Clinic which has reported its comparison of open and robot‐assisted radical prostatectomy in >10 000 patients. The oncological and functional outcomes are no different, open surgery is quicker and there is less blood loss and shorter time to catheter removal after robotic surgery. Just like the randomized trial of the two techniques, this large series highlights that surgeon experience rather than the technique is more important for clinical outcomes [5]. Finally, based on the STAMPEDE results, docetaxel is recommended for metastasis in addition to ADT and can be considered for high‐risk patients receiving ADT and radiotherapy [6]. NICE has also identified a number of important research questions which we hope will be answered by ongoing studies in coming years.

by Prokar Dasgpta, John Davis & Simon Hughes

 

References

  1. NICE Guidance. NICE guidelines prostate cancer. BJU Int 2019; 124: 9– 26.
  2. Loeb, S. Review of prostate cancer screening guidelines. BJU Int 2014; 114: 323– 5
  3. Ahmed, HU. The PROMIS of MRI. BJU Int 2016; 118: 7
  4. Merriel, SWD, Hetherington, L, Seggie, A et al. PCUK consensus statement. BJUI 2019; 124: 47– 54
  5. Haese, A, Knipper, S, Isbarn, H et al. A comparative study of robot‐assisted and open radical prostatectomy in 10 790 men treated by highly trained surgeons for both procedures. BJU Int 2019; 123: 1031– 40
  6. Sathianathen, NJ, Philippou, YA, Kuntz, GM et al. Taxane‐based chemohormonal therapy for metastatic hormone‐sensitive prostate cancer: a Cochrane Review. BJU Int 2019; [Epub ahead of print]. https://doi.org/10.1111/bju.14711

 

Editorial: Predicting sepsis after percutaneous nephrolithotomy

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In this month’s BJUI, Chen et al. [1] report on a large series of percutaneous nephrolithotomy (PCNL) procedures from Guangzhou in China. The authors studied patients who developed postoperative urosepsis and looked for any predictive factors that would herald impending sepsis.

In this latest report, the authors analysed 802 patients with complex kidney stones undergoing PCNL in a single centre. ‘Complex’ was defined as complete staghorn, partial staghorn or pelvic stone with at least two calyceal stones. Midstream urines (MSU) were collected and analysed for white blood cells (WBC) and nitrites (NIT). Antibiotics were given preoperatively if the urine culture (UC) was positive for WBC (WBC+) or NIT (NIT+). Standard single‐dose antibiotic was given on induction of anaesthesia and only continued for 48 h if the culture was positive. Stone cultures (SCs) were routinely collected. Of the 802 patients, UCs were positive (UC+) in 171 (21%) and SCs subsequently positive (SC+) in 30%. Postoperatively, 98 (12%) developed a fever, 62 (7.7%) developed systemic inflammatory response syndrome (SIRS), and 19 (2.4%) developed sepsis as defined by the quick Sequential (sepsis‐related) Organ Failure Assessment (qSOFA).

Multiple factors were significantly associated with sepsis: female sex (79% vs 40%), infection stone (47% vs 21%), long operating time ≥100 min (74% vs 45%), multiple accesses (32% vs 10%), UC+ (63% vs 20%), SC+ (89% vs 29%), fever (74% vs 11%), as well as being both WBC+ and NIT+ (63% vs 13%). Conversely, if WBC and NIT were negative (WBC–NIT–) the risk of sepsis was only 5.3%. On multivariate analysis SC+ (odds ratio [OR] 8.0), operating time ≥100 min (OR 4.4), WBC+ and NIT+ (OR 3.9), UC+ (OR 3.2), were independent risk factors for sepsis. Not surprisingly having UC+, SC+ or both showed a statistically higher incidence of fever, SIRS, and sepsis. Being WBC+ and NIT+ was the best predictor of having both UC+ and SC+ with an impressive 92% sensitivity and 98% specificity.* Similarly, WBC+ and NIT+ was the best predictor of sepsis with 92% sensitivity and 82% specificity. The absolute risk of sepsis was only 0.2% if WBC–NIT–, 2.8% if only one was positive, and 10% if WBC+NIT+.

The authors also report on the bacterial findings of the UCs and SCs. In the SCs, Escherichia coli (44%), Proteus mirabilis (14%) and Staphylococcus (7.4%) were the most common; whilst in the UCs, E. coli (54%), Enterococcus (9.4%) and P. mirabilis (7.6%) were predominant. It is important to remember the potential differences when interpreting UCs preoperatively and to ensure broad‐spectrum cover is given and this justifies the sending of SCs, particularly in high‐risk patients [1].

The recognition of early sepsis is paramount and has been recognised in previous studies leading to the ‘golden hour’, when early aggressive treatment of the infection has been shown to lead to better outcomes [2]. In a large study by Kumar et al. [2], early antimicrobial administration (within the first hour of hypotension from septic shock) led to a higher overall survival; but worryingly, only 50% of patients received appropriate antibiotics within 6 h. Thus, if high‐risk patients could be predicted then closer monitoring, aggressive fluid management, and early broad‐spectrum antibiotics with intensive care support could be targeted at those specific patients.

There are multiple definitions for infection, e.g., sepsis, severe sepsis, septic shock, and SIRS. The 2016 International Consensus attempted to clarify these and defined sepsis as ‘A life‐threatening organ dysfunction due to dysregulated host response to infection’ [3]. They found the term ‘severe sepsis’ to be obsolete. Septic shock is defined as ‘a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone’ [3]. The Consensus recommended organ dysfunction is assessed by a SOFA score increase of ≥2, as this is associated with a mortality of 10%. This then led to the bedside assessment clinical score called qSOFA. Poorer outcomes were associated with two or more of the qSOFA criteria: respiratory rate ≥22 breaths/min, altered mentation (as judged by the Glasgow Coma Scale), and systolic blood pressure ≤100 mmHg.

In this current study [1], many of the factors associated with postoperative sepsis are logical and have been demonstrated before, e.g., female sex, infection stone, prolonged operating times, and multiple accesses. This paper has shown that careful attention to the preoperative urine dipstick can provide important prediction of potential severe infective complications postoperatively. In an era of antibiotic stewardship this could help guide targeted preoperative and prolonged postoperative antibiotics for a small group of patients, whilst managing WBC–NIT– patients with standard prophylaxis only. The high‐risk group should also be observed very closely postoperatively and moved to a high‐dependence setting rapidly if clinical signs of sepsis develop. It would also suggest that in this high‐risk group, operating times and intra‐renal pressure should be minimised. It may be that in these patients it is better to use larger tract PCNL sizes to allow rapid fragmentation and evacuation of the stone and that consideration should be given to staged procedures in complicated stones where multiple access is being considered to minimise operating time and allow analysis of intraoperative SCs.

It should of course be remembered that antibiotic decisions should be based on local policies and sensitivities, which may be very different from this population. Rapid treatment of sepsis is paramount and the most recent ‘Hour‐1’ bundle provides the most up‐to‐date guidance for immediate resuscitation and management with lactate management, blood cultures, broad‐spectrum antibiotics, i.v. fluids, and early use of vasopressors if the blood pressure does not respond to fluid replacement [4].

by Matt Bultitude and Kay Thomas

References

  1. Chen, D, Jiang, C, Liang, X et al. Early and rapid prediction for postoperative infections following percutaneous nephrolithotomy in patients with complex kidney stones. BJU Int 2019; 123: 1041– 7
  2. Kumar, A, Roberts, D, Wood, KE et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med 2006; 34: 1589– 96
  3. Singer, M, Deutschman, CS, Seymour, CW et al. The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis‐3). JAMA 2016; 315: 801– 10
  4. Levy, MM, Evans, LE, Rhodes, A. The surviving sepsis campaign bundle: 2018 update. Crit Care Med 2018; 46: 997– 1000

*FileS1; FileS2

 

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