Correspondence
Reply to E.A. Rakha et al
We thank Rakha et al1 for their thoughtful comments and the
additional dimension that they have provided for our report on
borderline estrogen receptor (ER)positive cancers.2 We studied
gene-expression profiles of breast cancers that were 1% to 9%
ER-positive by routine immunohistochemistry (IHC) and found
that only a minority of these cancers had molecular features of
ER-positive, endocrine-sensitive tumors. Three different types of
assessment, including ESR1 mRNA expression,3 PAM50 molecular
class,4 and sensitivity to endocrine therapy gene signature5 consis-
tently indicated that the majority of these cancers showed molec-
ular features of ER-negative, basal-like cancers. We concluded that
in this rare subset of patients a second RNA-based ER assessment
may help to identify the minority of ESR1 mRNA-positive, luminal
type cancers, and as a result of the substantial uncertainty about
endocrine sensitivity in this population with borderline ER-
positive cancer, the safest clinical approach may be to consider
both adjuvant endocrine and chemotherapy.
Rakha et al1 point out an alternative method to gauge confidence
in the ER status of 1% to 9% IHC-positive cancers through a repeat ER
staining on the surgical resection specimen, particularly when the
initial hormone-receptor determination was performed on a core
needle biopsy. Their own IHC-based reassessment of borderline ER-
positive cancers agrees with our finding that only approximately one
quarter of these cases showed greater than 10% ER staining on repeat
IHC.6 On the basis of their report, we support the conclusion of Rakha
et al1 that a repeat ER IHC on the surgical specimen is a reasonable
Adoption of Robotic Surgery: An
Analogy From Urologic Oncology
TO THE EDITOR: The recent report by Wright et al1 compared
laparoscopic and robotic hysterectomy for endometrial cancer
using the population-based Perspective data set, which ac-
counts for 15% of nationwide hospitalizations. In the authors
analysis, they carefully controlled for multiple patient, surgeon,
and hospital factors and concluded that robotic assistance was
not associated with a decrease in perioperative complications or
length of stay, with the added disadvantage of increased cost
with the robotic platform. These conclusions seem to elegantly
follow from their analyses, the implications are not overstated,
and we congratulate the authors on their achievement. None-
theless, these results only provide a snapshot of the early adop-
tion of this new technology. Robotic prostatectomy, initially
described in 20012 and widely adopted at an unprecedented rate
in modern medicine,3 represents an ideal case study to examine
what may or may not happen with robotic hysterectomy in the
next decade.
Historically, open retropubic nerve-sparing prostatectomy
was considered the gold standard for surgical management of
localized prostate cancer. Laparoscopic prostatectomy was at-
tempted in the 1990s4 but did not gain much popularity in the
United States because of its prohibitive learning curve5 and is now,
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Copyright 2017 American Society of Clinical Oncology. All rights reserved.
approach to clarify the receptor status of borderline ER-positive can-
cers. We could not have possibly made a statement about the value of
repeat ER IHC on the basis of our work because we did not study the
value of repeat IHC.
Lajos Pusztai
University of Texas MD Anderson Cancer Center, Houston TX
Takayuki Iwamoto
Okayama University Hospital, Okayama City, Japan
AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Rakha EA, Lee AHS, Roberts J, et al: Low estrogen receptorpositive
breast cancer: The impact of tissue sampling, choice of antibody, and molecular
subtyping. J Clin Oncol 30:2929-2930, 2012
2. Iwamoto T, Booser D, Valero V, et al: Estrogen receptor (ER) mRNA and
ER-related gene expression in breast cancers that are 1% to 10% ER-positive by
immunohistochemistry. J Clin Oncol 30:729-734, 2012
3. Gong Y, Yan K, Lin F, et al: Determination of oestrogen-receptor status and
ERBB2 status of breast carcinoma: A gene-expression profiling study. Lancet
Oncol 8:203-211, 2007
4. Parker JS, Mullins M, Cheang MC, et al: Supervised risk predictor of breast
cancer based on intrinsic subtypes. J Clin Oncol 27:1160-1167, 2009
5. Symmans WF, Hatzis C, Sotiriou C, et al: Genomic index of sensitivity to
endocrine therapy for breast cancer. J Clin Oncol 28:4111-4119, 2010
6. Douglas-Jones AG, Collett N, Morgan JM, et al: Comparison of core
oestrogen receptor (ER) assay with excised tumour: Intratumoral distribution of
ER in breast carcinoma. J Clin Pathol 54:951-955, 2001
DOI: 10.1200/JCO.2012.43.5990; published online ahead of print at
www.jco.org on July 2, 2012
with few exceptions, rarely performed. Robot-assisted radical prosta-
tectomy (RARP) was introduced in 2001,2 and has now overtaken
open and laparoscopic approaches to become the predominant extir-
pative method for management of localized prostate cancer.3 Al-
though single-institution series6 have demonstrated oncologic
equivalence with open prostatectomy and possibly lower complica-
tion rates,7 several seminal articles8,9 have questioned the benefit of
robotic assistance. However, it is noteworthy that these reports were
based on early population-based series not dissimilar to the report by
Wright et al.1 Subsequent analyses, with more contemporary data3
from a wider geographic distribution,10 now demonstrate that RARP
is in fact associated with lower perioperative mortality, fewer overall
perioperative complications, and fewer late complications. Although
the learning curve is certainly one explanation, another intriguing
factor is that, whereas patients who underwent RARP in the early
population-based studies were older and had more comorbidities, the
opposite was seen in later population-based reports. The surgical
management of endometrial cancer has seen an evolution not unlike
that of prostate cancer; although randomized controlled trials11,12
have established the efficacy of laparoscopic hysterectomy, mature
data are understandably lacking for robotic hysterectomy, given the
recent emergence of this technology in gynecology.
Hence, we strongly agree, as indicated in the editorial by
Leitao,13 that robotic assistance for hysterectomy should not be
ignored on the basis of early comparative effectiveness outcomes.
RARP should provide an immediate and tangible testament to the
2012 by American Society of Clinical Oncology 2931
 Correspondence
drawbacks of extrapolating from such early results, and it would be
prudent to keep the evolution of RARP in mind when assessing the
benefits of robotic hysterectomy.
Shyam Sukumar and Jesse Sammon
Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI
Maxine Sun and Pierre I. Karakiewicz
Cancer Prognostics and Health Outcomes Unit, University of Montreal Health
Center, Montreal, Quebec, Canada
Quoc-Dien Trinh
Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI; and Cancer
Prognostics and Health Outcomes Unit, University of Montreal Health Center,
Montreal, Quebec, Canada
AUTHORS DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest.
REFERENCES
1. Wright JD, Burke WM, Wilde ET, et al: Comparative effectiveness of
robotic versus laparoscopic hysterectomy for endometrial cancer. J Clin Oncol
30:783-791, 2012
2. Menon M, Shrivastava A, Tewari A, et al: Laparoscopic and robot assisted
radical prostatectomy: Establishment of a structured program and preliminary
analysis of outcomes. J Urol 168:945-949, 2002
3. Trinh QD, Sammon J, Sun M, et al: Perioperative outcomes of robot-
assisted radical prostatectomy compared with open radical prostatectomy:
Results from the nationwide inpatient sample. Eur Urol 61:679-685, 2012
Reply to S. Sukumar et al
We appreciate the interest of Sukumar et al1 in our work2 and
are grateful for their kind comments regarding the analysis. We
examined the comparative effectiveness of robotic versus laparo-
scopic hysterectomy for endometrial cancer. We noted that mor-
bidity was similar for the two procedures, but cost was 14% greater
when the surgery was performed robotically.2 As suggested, these
findings derive from the early implementation of robotic hysterec-
tomy, and outcomes may improve with time. However, even by the
first quarter of 2010, the number of robotic procedures outnum-
bered laparoscopic procedures.
Sukumar et al1 compare the development of robotic hysterec-
tomy to that of robotic prostatectomy. Laparoscopic prostatectomy
was developed in the 1990s, but because of the technical difficulty of
the operation, it gained little traction.3 When robotic prostatectomy
was introduced, it offered a minimally invasive option that surgeons
could master as opposed to a traditional open approach that required
laparotomy. In contrast, laparoscopic hysterectomy, which was also
developed in the 1980s to 1990s, is now frequently performed for both
benign and malignant indications and is widely taught in gynecology
residencies and gynecologic oncology fellowship programs. Laparo-
scopic hysterectomy for endometrial cancer has been compared with
open hysterectomy in multiple prospective, randomized trials.4,5 Un-
like robotic prostatectomy, which essentially offers the only minimally
invasive surgical approach for prostatectomy, robotic hysterectomy
merely provides another minimally invasive option for a well-
accepted procedure. With usual surgical techniques, laparoscopic hys-
terectomy for endometrial cancer is often performed with fewer
2932 2012 by American Society of Clinical Oncology
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Copyright 2017 American Society of Clinical Oncology. All rights reserved.
4. Schuessler WW, Schulam PG, Clayman RV, et al: Laparoscopic radical
prostatectomy: Initial short-term experience. Urology 50:854-857, 1997
5. Vickers AJ, Savage CJ, Hruza M, et al: The surgical learning curve for
laparoscopic radical prostatectomy: A retrospective cohort study. Lancet Oncol
10:475-480, 2009
6. Menon M, Bhandari M, Gupta N, et al: Biochemical recurrence following
robot-assisted radical prostatectomy: Analysis of 1384 patients with a median
5-year follow-up. Eur Urol 58:838-846, 2010
7. Agarwal PK, Sammon J, Bhandari A, et al: Safety profile of robot-assisted
radical prostatectomy: A standardized report of complications in 3317 patients.
Eur Urol 59:684-698, 2011
8. Hu JC, Gu X, Lipsitz SR, et al: Comparative effectiveness of minimally
invasive vs open radical prostatectomy. JAMA 302:1557-1564, 2009
9. Hu JC, Wang Q, Pashos CL, et al: Utilization and outcomes of minimally
invasive radical prostatectomy. J Clin Oncol 26:2278-2284, 2008
10. Kowalczyk KJ, Levy JM, Caplan CF, et al: Temporal national trends of
minimally invasive and retropubic radical prostatectomy outcomes from 2003 to
2007: Results from the 100% Medicare sample. Eur Urol 61:803-809, 2012
11. Walker JL, Piedmonte MR, Spirtos NM, et al: Laparoscopy compared with
laparotomy for comprehensive surgical staging of uterine cancer: Gynecologic
Oncology Group Study LAP2. J Clin Oncol 27:5331-5336, 2009
12. Walker JL, Piedmonte MR, Spirtos NM, et al: Recurrence and survival after
random assignment to laparoscopy versus laparotomy for comprehensive surgi-
cal staging of uterine cancer: Gynecologic Oncology Group LAP2 Study. J Clin
Oncol 30:695-700, 2012
13. Leitao MM Jr: Potential pitfalls of the rapid uptake of new technology in
surgery: Can comparative effectiveness research help? J Clin Oncol 30:767-769,
2012
DOI: 10.1200/JCO.2012.42.4895; published online ahead of print at
www.jco.org on July 2, 2012
incisions (four v five) that are typically smaller in size (5 to 10 mm v 8
to 10 mm).
The second point raised by Sukumar et al1 is that comparative
effectiveness research cannot be applied to surgical technologies such
as robotic hysterectomy. We strongly disagree with this assertion. If a
new procedure does not result in improved outcomes or decreased
adverse effects but is associated with greater cost, how can we possibly
justify dissemination of the procedure? Although it is unrealistic to
hold surgical innovations to the same rigorous, evidence-based stan-
dards as new drugs, there is growing recognition that a more formal-
ized process of development is needed.6-9 The Balliol Collaboration
has proposed recommendations for more orderly testing and report-
ing of surgical innovations and techniques.6 Likewise, the Institute of
Medicine has recommended more stringent efficacy and safety stan-
dards for new devices that are approved through the US Food and
Drug Administrations 510(k) process.7,8 Finally, several investigators
have proposed a tiered reimbursement system for new treatments and
technologies in which comparative effectiveness data are linked to
payment.9,10 Although new surgical procedures should be encour-
aged, they must also be rigorously investigated before widespread
dissemination. In the era of cost containment in medicine, innovation
without tangible benefit is unsustainable.
Jason D. Wright
Columbia University College of Physicians and Surgeons; Herbert Irving
Comprehensive Cancer Center, Columbia University Medical Center, New
York, NY
Dawn L. Hershman
Columbia University College of Physicians and Surgeons; Mailman School of
Public Health and Herbert Irving Comprehensive Cancer Center, Columbia
University Medical Center, New York, NY
JOURNAL OF CLINICAL ONCOLOGY