The Many Faces of PD: Should We Consider Progression in a More Nuanced Way?

Historically, cancer treatments have been graded in large part by the “response rate” they produce, the reflection of the proportion of patients whose cancers demonstrate significant tumor shrinkage on imaging scans. While stable disease, which at least reflects no disease growth, is considered a reasonable, relative victory compared to evidence of the cancer growing, we consider a treatment as failing when the cancer grows. At the same time, in patients who are being monitored off of therapy, evidence of new or growing disease on scans is the leading indicator that it is likely time to start treatment.

But experienced oncologists understand that “progression” is not a binary, yes or no event.  Like the oft-cited example that Eskimos have 41 different words for snow, reflecting the varied types, oncologists are increasingly coming to recognize and describe a more nuanced range of what may still be broadly classified as progression but may arguably lead to different recommendations for patients, especially if patients have very different future treatment options available to them.

For example, it is common for patients who have a “driver mutation” like an EGFR mutation or ALK or ROS1 rearrangement to have a very good initial response that can last for many months or a year, then begin to demonstrate very slow progression of their disease, often still with far less disease than was present before they started treatment. This may be in the form of a single new nodule in the liver or lung or bone emerging against a background of still excellent response elsewhere, it may be one or more brain metastases that appear while a patient continues to have no evidence of progression outside of the brain (generally felt to be due to poor penetration of many systemic anti-cancer therapies into the central nervous system because of the “blood-brain barrier”), it may be multiple nodules all growing at a very slow rate in a patient who has no symptoms, or it may be one or more areas of disease growing far more quickly, often causing new symptoms.  Even beyond imaging findings, some physicians use PET scans to follow disease and may infer progression because the metabolic activity (standard uptake value, or SUV, on a PET scan) increases in a lesion, even if it hasn’t grown. Similarly, some clinics use “serum tumor markers” such as CEA or CA-125 to track what they conclude is the trajectory of the underlying cancer, which may show an increase in a blood test of a patient who feels well and whose scans show no changes.

At the same time, patients face these situations with different levels of anxiety, with varying side effects of their treatments or symptoms directly related to their cancer, with different burdens of treatment ranging from cost to frequency of infusions, and with a range of subsequent therapies to consider if they switch treatments.

With such a continuum of settings that all fit under the heading of “progressing disease” we’ll focus discussion during this week’s #LCSM Chat on how people would be inclined to manage cases that are all within the broad array that constitute disease progression but may lead to very different conclusions about how to proceed. So please reflect on what you would do if it were you, a family member, or patient of yours, and why?

T1) New lung nodules 1 yr after surg for st 2 LC, all growing slowly. Onc favors no Rx until faster growth/symptoms. Agree or Rx now? #LCSM

(New lung nodules 1 year after surgery for stage 2 lung cancer, all nodules growing slowly. Oncologist favors no treatment until new growth symptoms. Agree, or want treatment now?)

T2) ALK+, respond’g to 1^st line Xalkori -> 2 new brain mets, no other PD. After focal RT to mets, cont Xalkori or switch to new Rx? #LCSM

(ALK positive, responding to first line Xalkori, now with 2 new brain mets, no other areas of progressing disease. After focal radiation to brain mets, continue Xalkori or switch to new therapy?)

T3) EGFR mut+ st 4 NSCLC, respond’g on Tarceva -> now nodules growing minimally, feel fine. Onc favors no change. Agree or move on? #LCSM

(EGFR mutation positive, stage IV NSCLC, responding on Tarceva, now nodules growing minimally, patient feels well. Oncologist favors no change. Agree or move to new treatment?)

T4) EGFR mut+, st 4 NSCLC, on Tarceva, but now 1 new lung nodule, all else stable. Surgery, RT, &/or change systemic Rx? #LCSM

(EGFR mutation positive, stage 4 NSCLC, on Tarceva, now 1 new lung nodule, all else stable (no new or progressing disease). Favor surgery, radiation, and/or change systemic therapy?)

T5) Maint Alimta after response to carbo/Alimta for st 4 NSCLC; scans unchanged, but serum tumor marker (CEA) rising. Stay or change? #LCSM

(Patient on maintenance Alimta after responding to carboplatin/Alimta for stage 4 NSCLC; scans are stable, but serum tumor marker, CEA (carcinoembryonic antigen) is rising? Continue current treatment or change therapies?)

T6) How does tolerability of current Rx matter w/stable dzs? If slight progress’n on well tolerated med, higher threshold to change? #LCSM

(How does tolerability of current therapy matter in the setting of stable disease? If the cancer demonstrates very slight progression but the treatment is well tolerated, are you more inclined to continue the current therapy?)

T7) Would you be more inclined to change to new Rx early if likely to be more active, or do you value saving something for later? #LCSM

(Would you be more inclined to change to a new therapy early if it is likely to be more active, or do you value saving a more effective therapy for later?)

T8) If no change in surv or symptoms, does longer time to PD alone give incentive to do further intervent’ns, like RT to existing dzs? #LCSM

(If it doesn’t change survival or relieve symptoms, does the potential to increase the time of no progression on scans justify pursuing another therapy, such as radiation to existing areas of visible disease?)

Please join #LCSM Chat moderator Dr. Jack West on Thursday July 14 at 8 PM Eastern, 5 PM Pacific, as we explore this topic. If you’re new to tweetchats, please read this primer on how to participate in #LCSM Chats.