I received this question two days ago on SmartPatients.com "What do your docs say about Pap type 1?"
Good question. Here is my detailed response.
"So far, NO improvement in outcome over the last decade."
Slide 5 of Albirges' 2017 papillary RCC presentation (alt) stated "So far, NO improvement in outcome over the last decade." I ask Dr. Albirges for an update at each February's GUASCO, said the answer has been the same since 2017. Not surprising since there is little commercial interest in new drug development for rare diseases due to the small patient population. Just not enough customers to cover the cost of R&D. As such, Rare kidney cancer Patients are often included in trials using drugs developed for clear cell kidney cancer. However the underlying biology of the two cancer types is different, so (unless I missed something) there have been no recent breakthroughs. To paraphrase Tolstoy "Healthy kidneys are all alike; cancerous kidneys are each cancerous in their own way." Not only is the biology of p1RCC (Papillary Kidney Cancer) different from the biology of clear cell RCC, the biology of p1RCC tumors differ between patients. Worse still, the biology of metastases in the same patient often differ from one another. This variability (likely) makes different p1RCC cancers respond differently to the same treatments. So instead of diagnosis based on histology (microscopic examination) and treatment grounded on population-based studies, some hospitals started touting a "precision" ("Personalized", "N=1") approach a few years ago based on analyzing each patient genetically.
"Precision medicine is telling us what won't work"
When I recently asked Sandy Srinivas about the state of Precision medicine at Stanford, she said "Precision medicine is telling us what won't work". Pity. We had hoped it would tell us what -would- work. So. Diagnosis is improving. Treatment less so. Again this is not surprising. Cancer drug development is slow and costly. Just 6.6% of cancer patients currently see benefits from existing drugs. And at the current rate of progress, it would take more than 200 years for all existing patients to be helped. One approach to this problem is combination therapy. Multiple targets. Multiple drugs administered simultaneously. One issue here is that while each drug is tough to tolerate on its own (lesions on orifices, diarrhea, fatigue, etc.). Taking multiple drugs simultaneously can kill you.
One question I wasn't asked: "So what are you doing?"
Given that a white knight isn't likely to ride over the hill in time, I believe that patients with rare, unusable, terminal diseases ought control their own data and use it to get a seat at the table when research priorities are decided.
While, many patient advocacy groups raison d'etre is research funding, mine isn't. I'm helping Pete Kane set up hackathons for patients with rare conditions. The March 1st 2020 hackathon was the second one for me. Here, I (finally) managed to facilitate a process that moved from my genomic data to an actual therapeutic recommendation. The recommendation is sketchy (at best). But with each hackathon, I'm making the process better and better. Structurally, each hackathon is morphing into something between a conference and a tumor board. Geographically disparate teams work on the problem before the event, then meet, discuss their findings and make recommendations. One unexpected benefit of this distributed approach is that redundant work (e.g. each group running their favorite aligner) forces cross checking between competing groups at the beginning of each step and so minimizes "garbage in". And minimizing "garbage in" helps reduce (but not eliminate) "garbage out".
Making this work requires a hell of a lot of pro bono support the whole way through. James Hsieh helped form rarekideneycancer.org. My surgeon, UCSF's Dr. Max Meng and Tissue acquisition manager Tasha Lea got me the tissue and DNA sequencing for the first hackathon. Yale's Kaya Bilguvar and Christopher Castaldi (with encouragement from UCLA's Brian Shuch) did the RNAseq for the second one. Most of these teams are made of undergraduate or graduate students. Students from Alex Feltus' Labs at Clemson attended both of my hackathons and have created papers from both. Pete Kane of rttp organized the event and got the word out on the first one.
Now I can't stress enough how grateful I am to this group. That said, the center of each of these hackathons is not money from the government or private donors. The center is not some Drug that a pharma company hopes to repurpose for my disease. The center is the patient. And being at the center, the patient (and his immediate supporters) has a responsibility to make progress happen. The good news? Progress is happening. N=1 research is hot right now and rare diseases benefit from this trend.
When a plane's engines cut out at 35,000 feet, the crew has about 12 minutes to figure out the problem. An interviewer once asked the pilots of several planes that that -almost- crashed "What were you feeling at the end?". They expected something along the lines of "panic" or "Love for my family" or "My life flashed before my eyes." What was their universal response? They felt stupid. These were pilots. Men and women who had trained their whole lives to solve problems just like this. And when the moment came, they just weren't able to crack it in time.
So. I'm not feeling stupid just yet. Here's hoping you aren't either.