Reply to W.R. Robinson from Chi: re: “Is the Easier Way Ever the Better Way? (ovarian cancer/neoadjuvant therapy/surgery/references...)

 Blogger's Note: follows to prior posting/correspondence/dialogue; worthwhile reading this discussion/debate, note the common denominator in references
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Reply to W.R. Robinson

Reply to W.R. Robinson

1. Dennis S. Chi⇓

1. Memorial Sloan-Kettering Cancer Center, New York, NY

1. Corresponding author: Dennis S. Chi, MD, Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10065; e-mail: gynbreast@mskcc.org.

1. Robert E. Bristow

1. University of California, Irvine Medical Center, Orange, CA

1. Deborah K. Armstrong

1. Johns Hopkins Kimmel Cancer Center, Baltimore, MD

1. Beth Y. Karlan

+ Author Affiliations

1. Cedars-Sinai Medical Center, Los Angeles, CA

We thank Robinson¹ for his comments on our editorial, “Is the Easier Way Ever the Better Way?”² Robinson disagreed with our article on two points. First, he stated that it is “both disingenuous and unrealistic to… suggest that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer.” Robinson also expressed concern that we were suggesting that neoadjuvant chemotherapy (NACT) “somehow represents a failure on the part of the physicians who are taking ‘the easy way out.'”

To the first point, we did not say that fellowship-trained, Board-certified gynecologic oncologists are not capable of operating on women with advanced ovarian cancer. Rather, we wanted to highlight that the number of patients who receive suboptimal debulking could be reduced by collaboration with other surgical colleagues. Many gynecologic oncologists partner with urologists for complex continent urinary conduits after pelvic exenteration and with plastic surgeons for a myocutaneous flap after radical pelvic surgery, for example, and we believe that patients with ovarian cancer should also be offered the potential benefit of subspecialty surgical consultation if it will improve their overall survival. The complexity of preplanning surgical consultations for advanced ovarian cancer debulking surgery should not be any different than for these other surgical collaborations.

It is incumbent on the gynecologic oncologist to ensure that pressures to minimize operating room and intensive care unit usage do not compromise the surgical outcome for our patients.........

The author(s) indicated no potential conflicts of interest.

Previous Section

 

REFERENCES

1. ↵
   1. Robinson WR

   (2012) Neoadjuvant chemotherapy is rarely the easy way out. J Clin Oncol 30:1563.

   FREE Full Text
2. ↵
   1. Chi DS,
   2. Bristow RE,
   3. Armstrong DK,
   4. et al.

   (2011) Is the easier way ever the better way? J Clin Oncol 29:4073–4075.

   FREE Full Text
3. ↵
   1. Chi DS,
   2. Musa F,
   3. Dao F,
   4. et al.

   (2012) An analysis of patients with bulky advanced stage ovarian, tubal, and peritoneal carcinoma treated with primary debulking surgery (PDS) during an identical time period as the randomized EORTC-NCIC trial of PDS vs neoadjuvant chemotherapy (NACT) Gynecol Oncol 124:10–14.

   CrossRefMedline
4. ↵
   1. Vergote I,
   2. Tropé CG,
   3. Amant F,
   4. et al.

   (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953.

   CrossRefMedline
5. ↵
   1. Tiersten AD,
   2. Liu PY,
   3. Smith HO,
   4. et al.

   (2009) Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Gynecol Oncol 112:444–449.

   CrossRefMedline
6. ↵
   1. Chi DS,
   2. Eisenhauer EL,
   3. Zivanovic O,
   4. et al.

   (2009) Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm. Gynecol Oncol 114:26–31.

   CrossRefMedline

Correspondence: Neoadjuvant Chemotherapy (ovarian cancer) Is Rarely the Easy Way Out + references +discussion on gyn specialists/general surgeons

Blogger's Note: worthwhile reading/pondering...
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Neoadjuvant Chemotherapy Is Rarely the Easy Way Out

 To the Editor:

I appreciate the thoughtful analysis by Chi et al¹ in the November 1 issue of Journal of Clinical Oncology, in the article entitled, “Is the Easier Way Ever the Better Way?” Chi et al make a very literate argument against using neoadjuvant chemotherapy (NACT) for ovarian cancer, continuing a discussion that has lingered among oncologists for more than 25 years. The argument has heated up recently as a result of several prospective studies, particularly that of Vergote et al,² which showed no difference in survival in patients treated with either primary surgery or NACT.

I must, however, disagree with Chi et al¹ on two points. The first of these is the suggestion by the authors that patients with stage IIIC/IV ovarian cancer should routinely be referred to ultraspecialist centers that are capable of performing advanced upper abdominal surgery. In reality, the great majority of patients with ovarian cancer in the United States have been and will be treated in community settings for the foreseeable future. The professional societies that represent gynecologic oncology have for years strongly recommended that ovarian cancer be handled by fellowship-trained gynecologic oncologists. This effort has met with mixed success; in many communities it is still the norm for women with advanced ovarian cancer to be operated on by physicians with no special oncologic surgical training.......

plus references:

REFERENCES

1. ↵
   1. Chi DS,
   2. Bristow RE,
   3. Armstrong DK,
   4. et al.

   (2011) Is the easier way ever the better way? J Clin Oncol 29:4073–4075.

   FREE Full Text
2. ↵
   1. Vergote I,
   2. Tropé GC,
   3. Amant F,
   4. et al.

   (2010) Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 363:943–953.

   CrossRefMedline
3. ↵
   1. Tiersten AD,
   2. Liu PY,
   3. Smith HO,
   4. et al.

   (2009) Phase II evaluation of neoadjuvant chemotherapy and debulking followed by intraperitoneal chemotherapy in women with stage III and IV epithelial ovarian, fallopian tube or primary peritoneal cancer: Southwest Oncology Group Study S0009. Gynecol Oncol 112:444–449.

   CrossRefMedline

abstract: Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective 

To evaluate the predictive power of serum CA-125 changes in the management of patients undergoing neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).


Conclusions 
Patients who undergo NACT-IDS achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤100U/mL were highly likely to be cytoreduced to no residual disease.

abstract: Changes in serum CA-125 can predict optimal cytoreduction to no gross residual disease in patients with advanced stage ovarian cancer treated with neoadjuvant chemotherapy

Objective

To evaluate the predictive power of serum CA-125 changes in the management of patients under going neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) for a new diagnosis of epithelial ovarian carcinoma (EOC).

Methods

Using the Cancer Registry databases from our institutions, a retrospective review of patients with FIGO stage IIIC and IV EOC who were treated with platinum-based NACT-IDS between January 2006 and December 2009 was conducted. Demographic data, CA-125 levels, radiographic data, chemotherapy, and surgical-pathologic information were obtained.

Results

One hundred-three patients with stage IIIC or IV EOC met study criteria. Median number of neoadjuvant cycles was 3. Ninety-nine patients (96.1%) were optimally cytoreduced. Forty-seven patients (47.5%) had resection to no residual disease (NRD). The median CA-125 at diagnosis and before interval debulking was 1749 U/mL and 161 U/mL, respectively.

Comparing patients with NRD (no residual disease)  v. optimal macroscopic disease (OMD), there was no statistical difference in the mean CA-125 at diagnosis (1566 U/mL v. 2077 U/mL, p = 0.1).

There was a significant difference in the mean CA-125 prior to interval debulking, 92 v. 233 U/mL (p = 0.001).

In the NRD group, 38 patients (80%) had preoperative CA-125 ≤ 100 U/mL compared to 33 patients (63.4%) in the OMD group (p = 0.04).

Conclusions

 Patients who undergo NACT-IDS (neoadjuvant chemotherapy followed by interval debulking surgery) achieve a high rate of optimal cytoreduction. In our series, after treatment with taxane and platinum-based chemotherapy, patients with a preoperative CA-125 of ≤ 100 U/mL were highly likely to be cytoreduced to no residual disease.

Highlights

► Patients with advanced ovarian cancer treated with neoadjuvant chemotherapy have high rates of optimal cytoreduction.
► Preoperative CA-125 < 100 may indicate a high probability of debulking to no gross residual disease.
► A drop of > 80% in CA-125 during neoadjuvant treatment may suggest platinum sensitive disease.

abstract: Predicting platinum resistance in primary advanced ovarian cancer patients with an in vitro resistance index

PURPOSE:

We aimed to identify primary platinum resistance in epithelial ovarian cancer (OC) patients with FIGO stage III-IV disease by an in vitro drug-response assay and to correlate the findings with clinical response. We considered whether neoadjuvant chemotherapy or anatomic sample site and tumor heterogeneity would influence the results.

CONCLUSIONS:

This in vitro assay predicted primary platinum resistance, without misclassification of sensitive OC patients, and the results were significantly associated with PFS. We suggest that samples from primary tumor and metastatic samples have different responses to chemotherapy and that exposure to chemotherapy might induce in vitro platinum resistance.

not yet recruiting: Trial of (neoadjuvant) Chemotherapy in Ovarian, Fallopian Tube and Peritoneal Carcinoma - Full Text View - ClinicalTrials.gov

Trial of Chemotherapy in Ovarian, Fallopian Tube and Peritoneal Carcinoma

This study is not yet open for participant recruitment.

Verified January 2012 by University of Kentucky

First Received on January 18, 2012. Last Updated on January 26, 2012 History of Changes

Purpose

This is a prospective study to evaluate the hypothesis that platinum-based neoadjuvant chemotherapy followed by interval surgical debulking with platinum-based adjuvant chemotherapy is associated with improved maximal surgical cytoreduction rates, comparable survival, decreased morbidity, and increased quality of life in patients with International Federation of Gynecologic Oncology stages IIIC and IV ovarian, primary peritoneal, or fallopian tube cancer when compared to historical controls and to evaluate the hypothesis that cancer induced inflammation is a predictor of poor prognosis and response to therapy in this group of ovarian cancer patients.

Editorial: Primary surgery or neoadjuvant chemotherapy in ovarian cancer: What is the value of comparing apples with oranges?

Does intraperitoneal chemotherapy benefit optimally debulked epithelial ovarian cancer patients after neoadjuvant chemotherapy?

Abstract

Objective

To compare survival of ovarian cancer patients treated with neoadjuvant chemotherapy followed by intraperitoneal (IP) versus intravenous (IV) chemotherapy after optimal interval debulking.

Conclusions

Survival benefit associated with IP chemotherapy after optimal upfront surgery may not translate to the neoadjuvant setting.

Research Highlights

► Macroscopic residual disease is associated with worse prognosis.
► No difference observed in complete response between IP and IV treated patients.
► IP chemotherapy benefits may not translate to the neoadjuvant setting.

BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer

Abstract

Background: Neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients.

Patients and methods: We assessed BRCA1 messenger RNA expression levels in paraffin-embedded pre-treatment tumor samples obtained by transurethral resection from 57 patients with locally advanced bladder cancer subsequently treated with neoadjuvant cisplatin-based chemotherapy. BRCA1 levels were divided into terciles and correlated with pathological response and survival....

short video: commentary Dr Maurie Markman - Neoadjuvant Chemotherapy for Advanced Ovarian Cancer

Neoadjuvant chemotherapy in advanced ovarian cancer: What kind of evidence is needed to convince US gynaecological oncologists? Vergote I, Amant F, L

Note: Dr Vergote is one of Europe's top gynecologic cancer researchers; journal correspondence=pay-per-view ($$$)

Neoadjuvant chemotherapy in advanced ovarian cancer: What kind of evidence is needed to convince US gynaecological oncologists?

Vergote I, Amant F, Leunen K.

BRCA1 mRNA expression and outcome to neoadjuvant cisplatin-based chemotherapy in bladder cancer — Ann Oncol

Background:
Neoadjuvant chemotherapy has shown a modest benefit in muscle-invasive bladder cancer patients; however, the subset of patients most likely to benefit has not been identified. BRCA1 plays a central role in DNA repair pathways and low BRCA1 expression has been associated with sensitivity to cisplatin and longer survival in lung and ovarian cancer patients.

Conclusions:
Our data suggest that BRCA1 expression may predict the efficacy of cisplatin-based neoadjuvant chemotherapy and may help to customize therapy in bladder cancer patients.