Chapter 9: Metastasis. Now What. Or As I Would Call It: Fuck

By hans Casteels

This is the word everyone hopes never arrives, and when it does, it has the social grace of a brick through a window. Up to now, the game has been about control, containment, and probabilities that occasionally leaned in your favor. Metastasis changes the game entirely. Not just the stakes, but the structure. You are no longer in a finite game with a defined endpoint. You are in a repeated, dynamic game against an adaptive opponent, with incomplete information and limited resources. So let’s define the game properly, because vague metaphors are comforting and useless.

You can keep this vague and philosophical, or you can make it explicit. Most oncology decisions quietly revolve around a few measurable outcomes: overall survival, progression free survival, symptom burden, and functional independence. Everything else is commentary. For some, the objective remains maximal survival at any cost. For others, it becomes a balance between extending life and preserving its quality. For many, it shifts over time depending on how treatments affect daily living. If you do not define this explicitly, the system will define it for you, usually in favor of more treatment, more intervention, more everything.

From a game theory perspective, metastasis introduces dynamic optimization under uncertainty. You are no longer choosing a single strategy. You are choosing a sequence of strategies, each contingent on how the disease responds. Hormonal therapy, chemotherapy, targeted therapy, immunotherapy, radioligand therapy, intermittent treatment breaks. Each is a move in a longer sequence, and each move changes the state of the board. The key concept here is sequencing.

But you are not playing against a single, uniform opponent. Metastatic disease is heterogeneous. Different clusters of cancer cells can behave differently in different parts of the body, with different sensitivities to treatment. One lesion shrinks, another grows, and everyone pretends this is surprising. It is not. It is exactly what a diverse, evolving system does. This is why treatments rarely produce clean, uniform responses and why strategy has to account for uneven outcomes rather than expect symmetry.

There are players. You are one. The disease is the other. There are also secondary players with influence but not full control: oncologists, specialists, family. Their incentives overlap with yours, but not perfectly.

There is a state of the game. This includes tumor burden, location of metastases, symptom profile, prior treatments, and your current physiological reserve. The state evolves over time, both from treatment and from the disease itself.

There is a set of available actions. These are your treatment options: hormonal therapy, chemotherapy, targeted agents, immunotherapy, radioligand therapy, local interventions, clinical trials, and the decision to pause or defer. Each action changes the state of the game.

There are payoffs. Not abstract ones. Concrete ones: overall survival, progression free survival, symptom burden, functional independence, cognitive clarity, time not spent in treatment. Every move trades off across these dimensions whether anyone says it out loud or not.

There are constraints. Toxicity, cumulative side effects, access to care, eligibility for trials, financial cost, and the simple fact that you cannot do everything at once without consequences.

And there is time. The most underappreciated variable. Every decision affects not just the present state, but the set of future available moves.

That is the game. Now, how do you play it?

First, define your objective function explicitly. If you do not, the default strategy of the system is escalation. More treatment, earlier, longer. That may align with your goals. It may not. Some players optimize for maximum survival regardless of cost. Others optimize for a weighted balance of survival and quality of life. Most shift over time. That shift is not weakness. It is rational updating in a changing game.

Second, understand the nature of your opponent. Metastatic cancer is not a single entity. It is a heterogeneous population of cells with different behaviors and vulnerabilities. That is why one lesion shrinks while another grows. In game terms, you are facing a distributed opponent with multiple strategies running in parallel. Expect mixed responses. Plan for them.

Third, recognize that this is a sequential game with diminishing returns. Treatments are not independent moves. They are ordered. Each line of therapy tends to deliver less benefit for a shorter duration than the one before, often with greater cumulative cost. Using a highly effective therapy early may produce a strong immediate payoff but reduce the value of future moves once resistance develops. This is a classic intertemporal trade off problem.

Which leads to the central strategic principle: preserve optionality.

Do not think in terms of winning the current move. Think in terms of maximizing the value of the entire sequence of moves. Sometimes the optimal strategy is not the most aggressive one. It is the one that controls the disease sufficiently while keeping future options viable. This often looks like stabilization rather than eradication, management rather than knockout.

Fourth, incorporate the opponent’s adaptation into your model. Resistance is not an anomaly. It is expected. Every effective therapy creates selective pressure. Over time, resistant populations emerge. This is an evolutionary game, not a static one. The question is not if resistance will occur, but when and how you respond to it.

That brings you to switching strategies. This is a threshold decision. Switch too early and you abandon a still effective line. Switch too late and you allow avoidable progression. The solution is not intuition in the moment. It is predefined triggers: specific changes in imaging, biomarkers, or symptoms that prompt a move to the next strategy. Without this, decisions drift toward either inertia or panic.

Fifth, treat side effects as part of the payoff function, not as externalities. Fatigue, metabolic changes, bone health, cardiovascular risk, cognitive impact. These accumulate and directly affect your ability to continue playing the game. A strategy that maximizes tumor response but renders you unable to tolerate subsequent therapy is not optimal. It is short sighted.

This is also where palliative care belongs, and it is routinely misclassified. It is not a terminal move. It is a support strategy that increases your capacity to remain in the game. Better symptom control, better energy management, better psychological stability. These are not soft variables. They extend your playable horizon.

Sixth, accept that you are operating under imperfect information. More scans, more tests, more genomic data do not eliminate uncertainty. They reduce it marginally at a cost. Each additional piece of information should be evaluated based on whether it changes your next action. If it does not, it is not information. It is delay.

Seventh, expand your action set when possible. Clinical trials are often framed as late stage options, which is strategically backward. In many cases, earlier entry provides access to novel mechanisms before the disease and the patient are too compromised. In game terms, trials can introduce entirely new moves into a constrained system. That is not desperation. That is opportunity, if aligned with your objective function.

Eighth, account for multi player dynamics. Your oncologist may favor disease control. Your family may favor longevity or comfort. You are the only player exposed to all payoffs simultaneously. If you do not clearly state your objective function, other players will project theirs onto your decisions. That leads to strategies that are internally inconsistent.

Ninth, manage decision fatigue. Repeated high stakes decisions degrade cognitive performance over time. When that happens, players default to the path of least resistance or the strongest external recommendation. To counter this, you pre commit where possible. Define thresholds. Establish principles. Decide in advance how aggressive you want to be under specific conditions. This is not rigidity. It is protecting your decision quality over time.

Finally, accept that the payoff function is dynamic. What you value now may not be what you value later. Updating your strategy in response to changing preferences and conditions is not inconsistency. It is optimal play in a changing environment.

So metastasis. Now what?

Now you are playing a repeated, adaptive game with constrained resources and no fixed endpoint. The objective is not a single decisive victory. It is maximizing cumulative payoff over time: extending life, preserving its quality, maintaining optionality, and staying capable of making the next move.

It is a harder game. But it is not a random one. And as long as there are moves available, there is strategy.

If I may… And since this chapter is about playing a long game against something that adapts, shifts, and refuses to follow a clean script, it is worth pointing out that not all battles begin this way. Some begin with a fighting chance, provided the right equipment is there on day one. There is no paywall here and there never will be, because monetizing uncertainty feels like the wrong kind of enterprise. But if you are looking for a move that has a clear, immediate impact, my daughter Ashley is a NICU nurse at William Osler Health System, where premature and medically fragile newborns are not playing a long strategic game yet, they are trying to stabilize, breathe, and grow in their first days of life.

The most basic advantage we can give them is a proper start, and that includes something as unglamorous and essential as a NICU bassinet. We are raising funds to help purchase two of them, at roughly thirty thousand dollars each, which in the grand calculus of healthcare spending is both a small number and, somehow, always just out of reach. If this chapter is about preserving options and creating room to keep going, then this is exactly that, except at the very beginning of the timeline. A simple, concrete move that improves the odds before the game even gets complicated. Thanks a million, in advance.

The essays will remain free. The bassinets, unfortunately, are not.

https://gofund.me/a0fc0777e