Re: Volume Outcomes of Cystectomy—Is It the Surgeonor the Setting?

Morgan TM, Barocas DA, Keegan KA, et al.

J Urol 2012;188:2139–44

Experts’ summary:

In an effort to establish predictors of mortality after complex

oncologic surgery, Morgan et al. analyzed 7127 patients with

urothelial carcinoma of the bladder undergoing radical

cystectomy from the Surveillance Epidemiology and End

Results–Medicare-linked database between 1992 and 2006.

Specifically, they studied the relationship between surgeon

volume (SV) and hospital volume (HV) on overall mortality. SV

was grouped according to tertiles (1–3, 4–12, and >12 total

surgeries); HV was also grouped by tertile (1–15, 16–50, and

>50 surgeries).

Univariate analysis showed that low SV and low HV were

each associated with increased mortality; however, multi-

variate analysis established that HV rather than SV was

significant for survival after radical cystectomy. By includ-

ing HV in the SV model, the outcome was attenuated to the

point where SV was no longer statistically significant.

Conversely, the HV outcome relationship was unaffected by

the inclusion of SV, demonstrating that HV is an indepen-

dent predictor of mortality in the full model. Three-year

survival probabilities showed that improved survival with

increased SV in each HV stratum was not significant. In

contrast, there was a significant improvement in survival

with increased HV in the medium SV stratum ( p < 0.01) and

the high SV stratum ( p = 0.02).

Experts’ comments:

The correlation between HV and survival after radical cystect-

omy is discussed in this paper as both an independent pre-

dictor of survival and the element accounting for survival

when SV is analyzed. These results should not go unnoticed;

the advantages of a tertiary referral center are significant with

respect to increased HV in addition to superior perioperative

care, improved critical care, and multidisciplinary oncologic

expertise.

Other investigators have explored surgical mortality in

relation to HV and SV. The Leapfrog Group has implemented

Evidence-based Hospital Referral as a safety standard,

noting that for certain operations, there may be as much as a

threefold difference in surgical mortality across hospitals.

Birkmeyer et al. provide additional evidence for HV hospital

referral [1]. They used regression techniques to analyze

2.5 million procedures (six types of cardiovascular proce-

dures and eight types of major cancer resections) between

1994 and 1999. When the data were assessed as a

continuous logarithmic variable, HV was inversely related

to both observed and adjusted operative mortality rates.

Major urologic oncology surgery is high risk by nature

and requires subspecialized expertise beginning with the

preoperative assessment and continuing throughout the

hospital course and attentive postoperative follow-up.

High-volume tertiary centers provide these aspects of care

and, most important, give patients the best opportunity for

the expected oncologic outcome.

Conflicts of interest: The authors have nothing to disclose.

Reference

[1] Birkmeyer JD, Siewers AE, Finlayson EVA, et al. Hospital volume

and surgical mortality in the United States. N Engl J Med 2002;346:

1128–37.

Zachary Klaassen, Rebecca Shay, Kelvin A. Moses, Martha K. Terris*

Section of Urology, Department of Surgery, Medical College of Georgia–

Georgia Regents University, Augusta, GA, USA

*Corresponding author. Section of Urology, Medical College of

Georgia–Georgia Regents University, 1120 Fifteenth Street,

Room BA 8414, Augusta, GA 30912-4050, USA.

E-mail address: mterris@gru.edu (M.K. Terris).

http://dx.doi.org/10.1016/j.eururo.2013.12.032

Re: Intratumor Heterogeneity and Branched EvolutionRevealed by Multiregion Sequencing

Gerlinger M, Rowan AJ, Horswell S, et al.

N Engl J Med 2012;366:883–92

Re: Single-cell Exome Sequencing Reveals Single-

nucleotide Mutation Characteristics of a Kidney Tumor

Xu X, Hou Y, Yin X, et al.

Cell 2012;148:886–95

Expert’s summary:

Gerlinger et al. performed exome sequencing and other genetic

analyses on spatially separate samples from four primary renal

carcinomas and their metastatic sites. Xu et al. performed

exome sequencing on single cells obtained from a renal cancer

and adjacent normal kidney. Both studies found extensive

genetic heterogeneity, with different mutations detected at

different sites within the primary tumours and between a

primary tumour and its metastases. Gene expression signatures

associated with good and bad prognosis were detected in

different regions of the same tumour.

Expert’s comments:

When systemic therapy is used to treat metastatic cancer, it

may lead to tumour shrinkage and relief of symptoms, but this

remission is often brief and the tumour becomes resistant to

drugs. For targeted agents, such as tyrosine kinase inhibitors

(TKIs) used to treat renal cancer, resistance ensues because the

tumour uses alternative pathways to drive angiogenesis and

cell proliferation; this might occur through adaptation of indi-

vidual tumour cells or selection of surviving cells that are

already using alternative pathways. Currently TKIs are selected

based on the results of large randomised trials and are not

matched to individual characteristics of a patient’s tumour. The

hope of personalised medicine, under investigation at many

E U R O P E A N U R O L O G Y 6 5 ( 2 0 1 4 ) 8 4 3 – 8 4 8846