Dr. Jack West reviews the importance of assessing the degree of progression when interpreting whether to change treatment of a cancer. It is important to ask not only whether a cancer has progressed, but HOW it has done so, and how much?

1. Cancer Progression in
Shades of Gray
(50 Shades of Cancer Progression)
H. Jack West, MD

2. 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)

3. 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

4. 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.

5. • 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

6. • 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?

7. 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.

8. • 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

9. For questions, comments, and
further information, check out
CancerGRACE.org