Palliative Surgery and the Role of Surgery for Stage IV Cancer - Ricardo J. Gonzalez, MD Assistant Professor of Surgery University of Colorado
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Palliative Surgery and the Role of
Surgery for Stage IV Cancer
Ricardo J. Gonzalez, MD
Assistant Professor of Surgery
University of Colorado
Objectives • Discuss the classic management of advanced disease • Define palliation and palliative surgery • Review literature on palliative surgery and metastectomy • Make sense of anecdote and logical conjecture by employing well-characterized information for specific patient groups in difficult situations – “We want actual not virtual data” AH Harken 6am lab mtng 2000
“In the field of surgical oncology tumor
biology is king, patient selection is queen,
and technical maneuvers are the prince
and princess who try, but usually fail, to
usurp the throne.”
Cady Arch Surg 1997
Advanced/Incurable disease
• Classic teaching
– Chemotherapy is the treatment of choice
– Radiation only for symptomatic lesions
– Cure or even long-term progression free
survival is not likely
Advanced/Incurable disease
• Arguments against surgery
– Survival is driven by the rate and volume of
metastatic burden
– Unhealthy patients that can’t tolerate surgery
• Risk benefit ratio is heavily weighted toward the
risks
– Theoretical risk of “angering the tumor” or
“letting the air in”
• Elaboration of VEGF or other angiogenic factors
from anesthesia, surgical stress, blood transfusion
and various other unknowns
Advanced/Incurable disease
• Arguments for surgery
– Improving quality of life and symptom control
– Debulking gives chemotherapy a fighting chance
– Alter the metastatic cascade
• removing the primary tumor
• removing the metastases
– Removing the inhibitory peptides/molecules that
depress the local immune response to the tumor
enhancing the anti-tumor immunity to the remaining
tumor cells
Surgery and metastatic disease • Must decide and discuss the goals early • What are the goals? 1. Palliation – symptoms/QOL 2. Improve upon progression-free survival 3. End of life goals met with surgery 4. Curative intent
Is this really that important?
• Cancer is the 2nd most common cause of death
(1/3 diagnosed and 1/3 die)
• End of life care consumes 12% of national
health care expenditure and 27% of Medicare
expenditures.
• 12.5 % of surgical procedures are for palliative
reasons
Krouse Arch Surg 2001
What’s Needed?
• Miner et al Am J Surg 1999 348 publications
– primarily focused on morbidity and mortality, while
only 12% of studies considered pain relief, 2%
considered cost, and 17% evaluated QOL.
– Curative surgery is based on robust data and
evidenced-based decision making; palliative surgery
is not.
• What’s needed:
1. Better define palliative surgery
2. Study more meaningful end results and establish
standards for which logical and thoughtful decisions
can be made
Krouse Arch Surg 2001
Palliation
• Relieve symptoms for patients beyond cure when non-
surgical measures are not feasible, not effective, or not
expedient
• Palliation means patient should be better at the
completion of the procedure or treatment
“It is axiomatic that one cannot palliatively improve an
asymptomatic patient using a scalpel.”
– R. G. Martin, 1982Palliative Care – Evolution - Early Quotes from a palliative care doctor • “We are not team death” • “We are not a death squad” Quotes from those who do not understand palliative care • “Here come the grim reapers” • “Oh here they come dressed in black” • “They’ll just drug ‘em with morphine” • “If he’s not comatose now just give them a shot at him”
The Surgical Treatment of Cancer: A Comparison of
Resource Utilization following Procedures Performed with
Curative and Palliative Intent
Purpose - evaluate the immediate and short term resource
utilization needs of patients undergoing surgical
intervention with curative or palliative intent.
Methods - 302 pts identified as palliative (58) or curative
(244) and followed for 6 months
Findings
• Avg # of patient encounters no different
– Patients undergoing surgery for palliative intent require
equal resources
• Character of resources is different:
– palliative patients admitted for symptom control and had
fewer hospital free days
– curative intent utilized services directed at their continued
treatment.
Cullinane CA Cancer 2003Resource utilization for ovarian cancer patients at
the end of life: How much is too much?
Aim: compared hospital vs. hospice based
costs during last 60 days of life for ovarian
cancer patients
• Billing records were analyzed for inpatient
and outpatient costs.
Lewin SN Gyn Oncol 2005Resource utilization for ovarian cancer patients at
the end of life: How much is too much?
Results: 67 non-hospice and 17 hospice
• equivalent – histology, stage, platinum sensitivity, mean
number of chemotherapy cycles
26%
reduction
Survival for the two groups was the same
Lewin SN Gyn Oncol 2005Palliative Care – Evolution - Today
• Establish the patients’ goals
and personalize therapy based
upon those goals
• Symptom control for long term
pain management in terminal
patients
• Helping the family and the
patient cope with and accept
the situation
• Help achieve fullness of life
• Reduces end of life health care
costs by 25-40%
“Mobile Happy Hour”Palliative Care – Evolution - Today
• Have far-reaching effects outside what you see in the
hospital
• Should be involved earlier and with increasing
responsibility during the treatment of patients with
incurable cancers
When to involve the Palliative Care Team:
1. When your attending gives you the OK
2. When the labor of symptom control
outstrips the teams resources or
understanding
3. Difficult social or psychological situationPalliative Surgery
Metastectomy/Palliative
Early stage disease
Surgery
Risk
Benefit Risk Benefit
Surgeon’s role:
1. initial evaluation of the disease
2. local control
3. control of discharge and hemorrhage
4. control of pain
5. reconstruction and rehabilitationPalliative Surgery-Defined
• Primary goal is improving symptoms
caused by advanced malignancy
• Effectiveness – presence and durability of
patient-acknowledged symptom resolution
• Successful:
1. improvement in QOL
2. minimal morbidity and mortality
3. modest resource utilizationPalliative Surgery
Grade ECOG/WHO Major Surgery
0 Fully active, able to carry on all pre-disease performance
without restriction
1 Restricted in physically strenuous activity but ambulatory
and able to carry out work of a light or sedentary nature, Yes
e.g., light house work, office work
2 Ambulatory and capable of all self-care but unable to carry
out any work activities. Up and about more than 50% of
waking hours
3 Capable of only limited self-care, confined to bed or chair Maybe
more than 50% of waking hours
4 Completely disabled. Cannot carry on any self-care. Totally
No
confined to bed or chair – “Ah he’s only mostly dead and
mostly dead is partly alive.” – Princess Bride.
5 Dead – “The difference between alive and dead is dead
can’t fog the mirror.” – Nathan W. Pearlman, MDA Prospective, Symptom Related, Outcomes
Analysis of 1022 Palliative Procedures for
advanced Cancer
• The goal:
– “to prospectively follow all patients undergoing
a palliative operative or endoscopic procedure
during a one year period to obtain some of the
data that are required to guide sound clinical
decisions and allow more adequate patient
counseling.”
Miner Ann Surg 2004A Prospective, Symptom Related, Outcomes
Analysis of 1022 Palliative Procedures for
advanced Cancer
• Results: • Documented improvement in
– 823 initial procedures 80%
– 109 for recurrence – Median 135 days
– 90 for new sx’s. – Complication vs. none:
– Overall mortality – 11% 67% vs. 89%, (pA Prospective, Symptom Related, Outcomes
Analysis of 1022 Palliative Procedures for
advanced Cancer
Palliative procedure to control
symptoms or improve QOL
823 patients
Improved No Improvement
Symptoms
20% (164/823)
80% (659/823)
Symptom Free Additional Symptoms Recurrent
Symptoms
46% (303/659) 29% (191/659)
25% (165/659)
Median 135 days Median 58 days
Median 52 days
Miner Ann Surg 2004A Prospective, Symptom Related, Outcomes
Analysis of 1022 Palliative Procedures for
advanced Cancer
Miner Ann Surg 2004A Prospective, Symptom Related, Outcomes
Analysis of 1022 Palliative Procedures for
advanced Cancer
• Conclusions
– In select patients palliation can be expected
– Durability of symptom control may be limited
by the development of new symptoms
– Potential benefit may be limited by poor
performance, malnutrition, and no prior
cancer treatment
Miner Ann Surg 2004Palliative Surgery
• Miner TJ et al Defining • Similar findings
Palliative Surgery in – Palliation is achievable with
Patients Receiving great success
Noncurative Resections – Durability of palliation is
for Gastric Cancer. JACS short due to development
of new symptoms
2004
– Age, gross residual
• Miner TJ et al Symptom disease, pain and
Control in Patients With recurrence of local disease
Locally Recurrent Rectal (rectal) were predictors of
Cancer. Ann Surg Oncol shortened symptom control
2003Case Vignettes
• “If all you ever do is discuss your successes
and not your failures then you’ll never get
anything out if this job.”
Nathan W. Pearlman, MD
• “A man’s errors are his portals of
discovery.” James JoycePalliative Surgery
4 mos!!
• 55 yo male with RLE 1.3 mm melanoma. SNBx (-) in 2002.
• Hx of recurrences every year until he developed visceral mets.
• Multiple clinical trials
• Worsening left upper back pain, insomnia, and early satiety. ECOG 0
• OR – left adrenalectomy, known liver and pelvic nodes left behind.
• Home in 5 days. No pain, eating well and can sleep.Palliative Surgery
• 61 yo male presented with jaundice.
• CT showed pancreatic tumor
• Stent placed, chemo/XRT given, 5 stent changes during treatment due to
recurrent cholangitis. ECOG 0
• OR – Tumor unresectable, side-to-side Roux-Y hepaticojejunostomy and liver
abscess drainage.
• At F/U no more fevers, eating well and back on chemotherapy.Palliative Surgery
43 yo woman
• Colon obstruction and low
volume lung mets. ECOG 3.
• OR – Ex lap, en bloc
resection of distal panc,
spleen, splenic flexure, left
kidney, and diaphragm
• DC home in 2 weeks
• 1 mo. later brain mets and Would she have done better with a
palliative bypass?
peritoneal recurrence
“Whenever a man does a thoroughly
• 3 weeks later died stupid thing, it is always from the
noblest motives.” Oscar WildeWhat about metastatic disease?
Surgery and Metastatic Disease
• Can we alter the natural history of the disease?
– Does removing the primary alter progression-free or
overall survival?
• Is there any benefit to Stage IV NED?
• How do we select patients for surgery and keep
long term survival as our goal?
– Two approaches
1. The Pragmatic approach
2. The Academic approachPatient selection – Pragmatic 1. Is the patient insured? 2. Is the Oncologist a friend of mine or do I want him to be a friend of mine? 3. If not insured then is the patient loaded and will I get an endowed chair? 4. Any on-going studies for which I need patients? 5. Should I go snowboarding instead of taking this on? 6. Do I need a break from M&M? 7. Is there any patient benefit? (Last consideration)
Patient selection – Academic 1. Do we have a clinical trial in our center? 2. What is this patients performance status? 3. Are there any contraindications based on comorbidities? 4. Do I understand the disease progression for this particular patients tumor prior to considering surgery? 5. Is there any chance for patient benefit or can I improve upon his symptoms? (ALWAYS AT THE FOREFRONT OF THE ANALYSIS!!)
The Pragmatic
“After a while you spend so much time trying to
fend off the Grim Reaper you wonder if you’re
ever going to win or even why you’ve gotten
yourself into this mess.”
Nathan W. Pearlman on Rounds 2004
The Academic
“In the field of surgical oncology tumor biology is
king, patient selection is queen, and technical
maneuvers are the prince and princess who try, but
usually fail, to usurp the throne.”
Cady Arch Surg 1997Stage IV Melanoma
• Sobering statistics
– 0.76 – 1.5 mm 25% nodal mets in 3 yrs
– 1.5 – 4.0 mm 60% nodal mets in 3 yrs and
15% distant mets in 5yrs
• Site of distant recurrence predicts survival
– Nodal 20 – 50% at 5 yrs
– Visceral 5% at 5yrs
Balch CM. J Am Acad Dermatol 1980Stage IV Melanoma
Three criteria cited as predictive of survival after
complete metastatic resection – biology is king.
1. The site of metastasis
• visceral vs. nonvisceral
• visceral pulmonary vs. nonpulmonary
2. The number of metastatic lesions
• more is worse
3. The disease-free interval before the
development of metastases
• more than a year
Allen PJ ASO 2002Stage IV Melanoma
• Patient selection is queen
• 26,204 pts with melanoma
• 1,750 (7%)pts with liver mets
• 34/1750 (2%) explored (med DFS 58 mos
and 75% solitary mets)
– 16 aborted and 18 resected
– Of resected 5 (27%) were NED
– 0.3% of patients with liver mets!!
Rose DM Arch Surg 2001Stage IV Melanoma • Complete resection is the only technical maneuver that potentially alters the natural history of the disease – the princess. • Prior to proceeding forward with this approach you need a complete staging workup – H&P, labs (LDH), PET/CT scan – brain MRI and bone scan (symptomatic patients)
Stage IV melanoma –skin/soft tissue
• Most common (59%) initial site of distant recurrence is
skin, subcutaneous tissue and regional nodes.
• Complete resection
– Median survival as high as 50 months
– 5 year overall survival of 38%
• DFI has highest predictive value with best prognosis if
>18 months after primary resection.
• Surgical palliation is strongly encouraged because it is
easily accomplished with minimal morbidity.
Balch J Clin Oncol 1983
Allen ASO 2002Stage IV melanoma - Lung
Group 5yr (%) 3 Prognostic
N=328 pts pulmonary
signs
metastsectomy
I 29% CR, DFI>36 mos
and single met
II 20% CR and one
unfavorable
III 7% CR and two
unfavorable
IV 0% Incomplete
resection
Median 19 vs. 11 mos, pStage IV melanoma – GI tract
• N=68 pts explored • Group I curative
resection
• Anemia 60% and pain
59% • Group II residual
disease
14.9 vs. 6.9 mos
median survival
Median = 6.9 mos
5 yr = 18% Curative
Residual disease
Agrawal S ASO 1999Stage IV Cancers and Metastectomy
Author Year N Site/disease Predictors of survival
Pawlik 2007 52 Liver/SCCA Complete resection, longer DFI,
Size12mos
Fong 1999 1001 Liver/colorectal Complete resection, DFI>12mos,
Liver only, Tumor number, node (-)
10, Met< 5cm, CEALiver Metastectomy and Pancreatic Cancer?
• N = 22 patients with low volume
synchronous liver mets (86% solitary)
• Results
– Whipple (no mets) - 14.2 mos median
– Palliative bypass – 5.6 mos median
– Whipple + liver resection – 5.9 mos median
• Conclude
– Even with well selected patients biology wins
with metastectomy and pancreatic cancer.
Pawlik Cancer 2007Peritoneal Surface Disease from Colorectal Cancer:
Comparison with the Hepatic Metastases Surgical
Paradigm in Optimally Resected Patients
• 121 IPHP vs. 101 Liver • Completeness of
resections cytoreduction
• Compared R0/R1 IPHP – R0, complete removal of all
vs. R0 Liver resections visible tumor and negative
cytology or microscopic
– Morbidity and mortality margins
– Overall survival – R1, complete removal of all
visible tumor and positive
cytology or microscopic
margins
– R2a < 5mm
– R2b 5mm – 2cm
– R2c >2cm
Shen Ann Surg Oncol 2008Peritoneal Surface Disease from Colorectal Cancer:
Comparison with the Hepatic Metastases Surgical
Paradigm in Optimally Resected Patients
• M&M (PSD vs. HM)
– 48.1% vs. 33.7% (p=0.38)
– 5.5% vs. 4.2% (p=0.71)
41 mos
• MV predictors
34 mos
– Resection status,
obstruciton, malignant
ascites and LOS
Concluded: R0/R1 resection during
IPHC compared with margin-negative
5yr OS was 26% vs. 34% hepatic resection demonstrated no
significant difference in OS and
should be considered a viable
treatment option.
Shen Ann Surg Oncol 2008Surgery and Stage IV Disease: should
we remove the primary?
• Yes if
– The lesion is symptomatic or will soon become
symptomatic
– The disease classically responds to chemotherapy
– Patients can live a long time with mets
– Removing the lesion can be achieved with low
morbidity
• No if all of the above do not applyRemoving the Primary and Survival
Author Year N Disease Conclusions
(resected)
Saidi 2006 105(24) Gastric Improves OS (13.2 vs. 5.5
mos)
Field 2007 409 (187) Breast Improves OS(31.9 vs 15.4
mos), not metastatic PFS
Babiera 2006 224(87) Breast Improves metastatic PFS
(p=0.001) and trend toward
OS (p=.1)
Blanchard 2008 395(242) Breast Improves OS (27.1 vs.16.8
mos)Removing the Primary and Survival • Overall Survival and • Overall Survival and Surgery Surgery Babiera et al Field et al
Removing the Primary and Survival
• Metastatic PFS and • Metastatic PFS and
Surgery - improved Surgery – no
difference
Babiera et al Field et alDo tumor-bearing patients have decreased
tumor immunity?
• Multiple hypotheses
– immune tolerance of the host to tumor antigens1
– genetic changes in tumor cells that render the tumor cells
“immune” to the host’s immune system2-4
– “ignorance”or lack of activation to tumor antigens5
– dysfunction of potentially tumor-reactive lymphocytes
rendering them unresponsive to antigen6
– immune suppression mediated by tumor cell secretion of
inhibitor factors and/or activation of systemically
immunosuppressive cells7,8
1. Pardoll D Ann Rev Immunol 2003 5. Ochsenbein AF Nature 2001
6. Fink J Immunol Today 1999
2. Seliger B Immunol Today 2000
7. Kusmartesev S Cancer Immunol Immunotherapy 2002
3. Marincola FM Adv Immunol 2000 8. Shevach EM Nature Rev Immunol 2002
4. Seliger B Semin Cancer Biol 1999Summary
Goals should be patient-directed and discussed early
Palliative surgery should be considered after careful patient
selection
• Success is determined by:
1. Symptom resolution or improved QOL
2. Minimal morbidity and mortality
3. Modest resource utilization
Surgery for stage IV disease can be undertaken with curative
intent
1. DFI > 12 months
2. Performance statusThank you!
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