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Radical Surgery: Keep The Lung? Or Let It Go?


Chart - "Six recent studies on mesothelioma surgery-a toss up?" lists medical research that probes deeply into the issues associated with mesothelioma treatment and survival. Take a look, but don't take comfort that the best and brightest are on the case. Few of these trials are available in the U.S., where research money for mesothelioma is depressingly tight.

"If a patient has a big, bulky tumor, you need to use EPP, period."

Dr. Raja Flores, M.D., thoracic surgeon and surgical oncologist

Chart - "The mother of all clinical trials?" lists the only randomized clinical trial ever held to test the efficacy of mesothelioma surgery versus non-surgery. Unfortunately, the trial only tests EPP and is only available in the United Kingdom.

Chart - "Keep the lung or lose it? A comparison of the PD and the EPP," breaks down the key differences between the two surgeries. Read it closely. Many of us have been taught that PD is "palliative," a word that suggests the operation is hardly worth the effort, like putting a band-aid on a gashed hull. Many of us presumed that the only chance a patient had for a five-year survival was to head to Boston and have his lung amputated. And yet the published data surprisingly shows that in many cases the PD numbers are better than EPP's. In truth, all surgical procedures to date could and should be considered "palliative."

Why surgery? Surgery designed to remove all possible tumor-invaded or contaminated tissue is radical surgery. Because mesothelioma is a diffuse tumor, and because surgery itself can spread the cancer cells, in order to eradicate all tumor the surgeon would have to cut out the ribs and intercostal muscles, the pleura, lung, trachea, pericardium, diaphragm, esophagus, superior vena cava, aorta, subclavian artery and vein, nerves, and vertebral bodies. Essentially, whack out everything below the neck and above the gut, and you'll be "cancer free." You'll also be dead.

"The bulk of the tumor doesn't matter in selecting the type of surgery, but rather the invasiveness of the tumor is the key. In general, non-invasive tumors can be removed equally well by either surgical technique, if performed by an adequately-trained, meticulous surgeon. By the same token, if the tumors are invasive, then they cannot be removed adequately regardless of the surgical technique."

Dr. Robert Cameron, M.D., thoracic surgeon and surgical oncologist

Both PD and EPP are controversial in that no randomized clinical trial validates either over the other, or even over no treatment at all. The medical benefit of EPP over PD has never been shown, although there are good indications that PD is associated with longer survival. Some surgeons perform both the EPP and the PD. Indeed, Boston is regarded as the home of the EPP, but recently Dr. Sugarbaker's team has been offering the PD as well. How does a "switch hitter" surgeon decide which operation is best? Dr. Harvey Pass of NYU has said he can't really tell until he pops the hood and takes a look inside. Apparently, the more "bulky" a tumor is, the less inclined the surgeon is to do the PD. The problem is that there is no standardized "bulk" threshold, i.e., how heavy and how extensive, questions which can probably only truly be answered if the tumor is cut away from the lung, either intraoperatively via the PD or later after the tumor-encrusted lung has been amputated. As with obscenity, for the bulk-sensitive surgeon, you just know it when you see it.

With the advancement of science, the sun usually sets on ultra-aggressive surgeries. Radical surgery for breast cancer, sarcomas, and colonic cancer have all evolved into narrower, meticulous operations. There is reason to believe that mesothelioma surgery will eventually conform to this approach, favoring the meticulous and careful surgery of the PD.

Even then, it's clear to this author that, just as not all EPP's are performed with equal skill, neither are all PD surgeries. At a recent MARF conference in Washington, D.C., an oncologist informed the largely patient audience that the PD was a relatively "quick" procedure. I've witnessed three PD's performed at UCLA. From opening to close, each took about ten hours of painstaking and meticulous surgery in order to remove all visible tumor from the chest, while sparing the lung, diaphragm, and pericardium.

During one procedure, another surgeon walked in, saw the massive operation, checked his watch, shook his head and half-joked: "I'll bet you could amputate the whole thing and get three of these operations done in the time it takes you to do one." It turns out that this jest hits close to the truth, as Medicare pays a higher reimbursement to the surgeon who does the EPP over the PD. Reminds me of what my journeyman boilermaker used to say back in the summers when I was a helper at the Exxon refinery in Baytown, Texas: "The less you work, the more you get paid."

Survival: the golden ring

Patients are hesitant to give up a lung, and this ends up being the strongest argument for them to go with PD. The issue of greatest concern to patients, "Will I survive the operation?" falls squarely in the PD camp. The numbers vary between surgeons, but the literature shows that surgical mortality for the PD is substantially less than the EPP (with less physiologic stress as well) while another study of 384 patients showed deaths from PD at 3%, as compared to 5% for EPP.

"It is argued that surgeons must offer hope-but surely not false hope by obscuring the truth from those who are entitled to know it. Active treatment for which there is no evidence of clinical benefit is sometimes preferred to inaction for 'psychological reasons.' EPP is too severe to be justified on these grounds, whether it is to comfort the patient or the surgeon."

Dr. Tom Treasure, M.D., thoracic surgeon and surgical oncologist

In addition, doctors agree that it's only a matter of time before the tumor recurs. Patients tend to like their chances better if they have two lungs instead of just one. And the distinction between whether the tumor recurs "locally" in PD or "distant" with EPP is not terribly important, as the seeding of tumor during surgery makes virtually every body cavity "local." The lawyer should also note that since the asbestos fibers are distributed between the left and right lungs, if the left lung is removed (or vice versa), experience shows that the same pathogenic disease process will often rear its ugly head in the adjoining lung.

See Chart H, "Example of data misrepresentation." Bad data can be easily found in the very places that patients most commonly troll for answers. I co-founded the Mesothelioma Applied Research Foundation, but even this highly respected institution sometimes provides questionable data. On its website, MARF has posted a table that purports to correlate the median survival with various treatment modes. Without citing any author, it lists the survival for the PD as 13 months, rather than the correct figure, which is between 19 and 22 months depending on the institution or surgeon who does the surgery. That's how hard this is, and that's how difficult it is to come by reliable data.

Buying more quality life

Helping a mesothelioma client means more than winnowing out the best survival data. Clients want to know about quality of life. If their ship is going down, and their time is sorely limited, few want to spend precious days, let alone months, going through horrendous recoveries. They want treatment that will allow them the quality of life to enjoy the time left with their families and friends. We were unable to find a single study examining quality of life for different mesothelioma treatments, and even studies that only look at a single treatment modality rarely address quality of life associated with a given procedure. The upcoming UK trial discussed previously is groundbreaking because it also considers quality of life issues associated with EPP v. chemotherapy.

Consider doing more for your client than counseling him to leap into the first lifeboat. Helping him ask the tough questions to any doctor pushing a particular treatment benefits everyone. We may want to fixate on statistics and numbers, but clients may rank quality of life "intangibles" as their top priority. It's imperative that the lawyer and the client understand foreseeable complications no matter the therapy, and always have at the ready a back-up plan.

Chart : Six recent studies on mesothelioma surgery-a toss up?

The following studies attempt to correlate median survival, surgical mortality, and prognostic factors with the PD and EPP.



Result s



Compare outcomes of PD v. EPP\

Non-randomized study

57 patients. EPP (45); PD (22)

PD patients much older than EPP patients (median age 62 v. 58);

Mean survival
for PD: 16 mo
15 mo for EPP

Sparing lung in older group does not compromise survival. Hospital ceases to do EPP in N2 cases; stages new patients with

Martin-Ucar et al, Europ Jrnl Cardio-Thor Surg. 31:5, 2007.

Compare outcomes of PD v. EPP

Non-randomized study

663 patients from 3 large hospitals (1990-2006); avg. patient age 63

Median Survival for EPP: 12 mo (385 pts);

PD: 16 mos. (278 pts).

EPP patients 20% higher risk of death. Both groups similar rate recurrence.

PD better outcomes, but PD patients earlier stage (Flores).

Non-epithelioid tumor 50% increased mortality; stage 3 & 4 90% higher mortality.

Flores et al, Am Assoc Thoracic Surg, annual mtg. Sept. 2007.

Phase II study to investigate four modality treatment late stage MPM

Non-randomized study

49 patients, stage 2-3, 1999-2004.

Treated with: pre-op interleukin-2, PD, post op epidoxorubicin + interleukin-2 + systemic chemo (gem/cis) + subcutaneous Interleukin-2

Mean age: 61

No surgical morbidity.

Median survival after 59 months is 26 months; 13 patients still alive.

Quad-modal therapy feasible, well tolerated, and produced favorable median survival. Most patients able to complete regimen.

Lucchi et al, Jrnl of Thoracic Oncology. 2(3): 237-242, March 2007.

Assess complications and risks of EPP after chemo

Non-randomized study

74 patients who got EPP followed over 59 months, mean age: 57

20% got induction chemo

85% patients stage III-IV

Post-op mortality: 6.7% & 67% had significant morbidity/complications, e.g. atrial fib, pneumonia, acute lung injury and mediastinal shift w/ tamponade.

EPP associated with high morbidity. EPP after chemo requires extra vigilance to prevent respiratory complications

Stewart et al, Euro Jrnl Cardio-Thoracic Surg. 27(3), Mary 2005.

Retrospective analysis of limited surgical treatment of MPM at UK hospital over 10 years.

Non-randomized study

70 patients, 1989-1999, avg age: 66

Divided into 3 groups:

1) Open biopsy only (21%)

2) Talc pleurodesis (58%)

3) Pleurectomy for stage 1 MPM, restricted to parietal pleura (21%)

Median Survival:

Group 1: 6 mos.

Group 2: 6 mos.

Group 3: 14 mos.

Low operative mortality for PD patients

EPP avoided b/c of high morbidity (50%) and low survival (10-19 mo)

Only do PD if tumor confined to parietal pleura (stage 1)

PD cost effective, well tolerated, few complications, minimally invasive, open to adjuvant therapies, and has survival rates similar to more radical EPP

Phillips et al, Interact. Cardiovasc & Thor Surg. 2:30-34, 2003.

Comments: Sugarbaker and Rusch claim no proof PD prolongs survival, yet EPP studies have a huge patient selection bias. Why limit PD to parietal pleura?

Identify MPM prognostic factors at large hospital (MSK)

Non-randomized study

945 patients, mean age: 66, 1990 to 2005

EPP: 22%, PD: 19%

Multi-modal therapy: median survival of 20.1 mos.

Predictors of survival: tumor type, staging, gender, asbestos exposure, smoking, symptoms and laterality

Flores et al, Jrnl of Thoracic Onc. 2(10): 957-965, Oct 2007.

Chart : The mother of all clinical trials?



Result s



Randomized trial w/ 2 groups:

1) chemo + EPP + radiation

2) chemo alone

All patients surgery eligible

Recruiting 50-670 MPM patients, must be resectable

Multiple centers in UK. No US hospitals participating.

To be determined.

Compare overall survival.

Compare quality of life for both groups.

A pioneering study, but it requires an EPP and does not allow a PD. Will not address whether survival would be better with PD and adjuvant treatment.

Institute of Cancer Research, UK. Info provided by NCI, Identifier: NCT00253409, Oct. 2007. This trial is not available in the U.S.

Chart : Keep the lung or lose it? A comparison of the PD and the EPP



Resection Margins

Best result is R1 margin, or removal of all gross/visible tumor


Surgical Tumor Spread

Surgical wound expanded into pericardium and peritoneum. May spread cancer to other areas.

Surgical wound limited. Diaphragm and pericardium spared if at all possible (>80%)

Post Op Radiation Therapy

Clear field available, but adjacent liver, stomach, heart at risk for radiation toxicity. IMRT of questionable benefit.

Detailed techniques with lung blocking can deliver radiotherapy w/ lung intact and minimal toxicity

Patient Selection

No co-morbidity, adequate lung reserve, younger (mean age < 60 years)

Older patients, 60-70+ y/o, later stage disease, lower performance status okay

Operative Procedure

More uniform: removal of parietal and mediastinal pleura, diaphragm, pericardium and lung

More variable: at UCLA, complete removal of visceral pleura, all gross tumor removed, regardless of "extent" or "bulk" of tumor, including removal from pulmonary fissures. Lung, pericardium (most often), and most of diaphragm spared.

Adjuvant Therapies

Chemo applied before, during or after. Radiation post-operatively.

Same. At UCLA, PD considered equivalent or superior to EPP and part of aggressive multimodality therapy


Because surgical wound extends into pericardium and diaphragm, tumor recurs in "distant" location but this is really "local" extension. New cancer in remaining lung may occur because asbestos exposure creates a field defect. High rate of recurrence in short time.

9 months median recurrence in one PD study at Brigham and Women's of 44 PD with intraoperative chemo lavage.


17-22 months median survival (Maziak 2005).

Higher survival may reflect creative patient selection (Meerbeeck, 2005).

17-22 months median survival (Maziak, 2005).

Operative mortality

5.9 - 14% (Maziak, 2005)

0% to 5.4% (Maziak, 2005)

Physician Benefits

Shorter operative time (3-5 hours); higher reimbursement ($1,380-1,848) (Cameron 2006); easier radiation therapy planning.

Longer operation (4-12 hours; lower surgical fee ($1,207 to 1,703) (Cameron 2006); comfort of doing less harm.


Experienced cancer centers, preferably as part of prospective randomized clinical trials (none currently active or even planned in the U.S.)

Same. Surgeon must be meticulous and perseverant, removing all gross tumor from chest wall, lung, and surrounding areas. Shouldn't be done as "fall back" procedure for those patients who cannot have EPP due to extensive disease

Aelony Y, Thoracoscopic talc poudrage in malignant pleural effusions: effective pleurodesis despite low pleural pH, Chest, 1998

Cameron R, Extrapleural pneumonectomy is the preferred surgical management in the multimodality therapy of pleural mesothelioma: con argument, Annals of Surgical Oncology, 2006

Ismail-Khan R, Robinson L, Id.