Cancer Progression in Shades of Gray

(50 Shades of Cancer Progression)

H. Jack West, MD

Cancer Progression is Not Black and White

• Though we follow certain concepts when cancer progresses, typically favoring a change of treatment, the real world of cancer treatment shows us that “progression” is not just a binary effect. Progression can fall anywhere on a continuum from minimal to very striking.

Major progressionStability

(a big area with room for judgment)

Is the Progression Glass Half Empty or Half Full?

• The first question is whether progression is CLINICALLY SIGNIFICANT. Should any change in treatment be initiated?

• Not necessarily for a very subtle form of progression that is of dubious clinical significance, such as these:

• Serum tumor markers rising without evidence of progression on imaging studies (when the cancer is measurable on scans)

• Minimal, subtle progression on scans (do you need to squint to see a change?)

• Changes in metabolic uptake on PET only, with stable size of lesions

Is Progression Localized or Diffuse?• Once you’ve determined that progression is

enough that it requires intervention, it’s appropriate to ask whether progression is in one/few spots (sometimes called “oligo-progression”) or in multiple areas.

• Progression in one area, with the rest of the cancer well-controlled, may be an issue of treatment not getting into a “sanctuary site” like the brain (many medications can’t penetrate through the blood-brain barrier).

• It may be feasible to do a very limited treatment like focal radiation or a small surgery to treat that rogue area of progression, otherwise continuing systemic treatment without changes.

• More diffuse progression typically necessitates a change in systemic therapy.

• It is not uncommon to see a “mixed response” of some areas of cancer responding well to treatment alongside one or more areas of progression and/or new disease.

• While you could potentially view all progression as reason to change, most experienced oncologists assess the balance of how much disease has responded vs. how much has progressed. If progression >> response, change treatment.

Mixed Responses

Responding disease

Progressing/new disease

• The crux of decision-making around progression is whether continuing the current treatment is better than all of the competing options available (sometimes including stopping treatment and focusing on symptom management and not pursuing more anticancer treatment).

Assessing All of the Options

Key questions:

1) Are there appealing treatment alternatives available? If yes, have a lower threshold to change therapy than if there are few good options.

2) Is the alternative to slow progression on the same treatment faster progression off of it? Or is the treatment possibly worse than the disease?

Tolerability: The Other Side of the Equation

• What does this mean? The better tolerated a current treatment is, the more inclined we can be to continue it when progression is a matter of judgment.

• If someone is having a challenging time tolerating a current treatment and showing any progression on it, move on.

• Anticipated benefit of treatment is only half of the equation.

• The other half is tolerability of treatment options.

• Progression isn’t simply a defined line in the sand at which treatment needs to change.

• Within the spectrum of progression, different factors can lead us toward or away from recommending a change.

• The less diffuse and striking the progression, the better tolerated the current treatment is, and the less impressive the subsequent options are, the less inclined we should be to change treatment (think, “the devil you know is better than the devil you don’t”).

• The more extensive and profound the progression, the less well tolerated the current treatment is, and the more appealing the competing alternatives are, the more inclined we should be to change systemic treatment.

Conclusions: 50 Shades of Progression

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