PD-L1 expression changes from yin to yang after chemoradiotherapy, bringing opportunities for immunotherapy

Bladder cancer is a malignant tumor arising from the malignant proliferation of bladder cells.
The risk of males is more than three times that of females, and its risk increases with age
.

According to the degree of invasion, it can be divided into invasive bladder cancer and non-invasive bladder cancer
.

The current treatment measures are mainly surgery, combined with chemotherapy and immunotherapy
.

Treatment of invasive bladder cancer is generally with platinum-based chemotherapy
.

Due to the rise of immunotherapy, immunotherapy represented by PD-1 inhibitors has made great efforts in the field of bladder cancer treatment
.

The KEYNOTE-045 study showed that if bladder cancer patients progressed after first-line chemotherapy, using immune checkpoint inhibitors in the second-line can achieve better benefits
.

If the PD-L1 expression in the patient's tumor tissue samples is relatively high, it is possible that the effect of immune checkpoint inhibitor therapy will be better, but this conclusion is still controversial
.

Let's first look at a case report related to it
.

PD-1 Inhibitor Therapy for Bladder Cancer Achieves Long-Term Remission A 69-year-old Japanese man presented with hematuria
.

The patient had a history of non-muscle invasive bladder cancer at age 57 and was treated with transurethral resection of the bladder tumor.
The pathological result was bladder diverticulum in situ carcinoma.
After surgical resection, he received no other treatment
.

After a lapse of 12 years, the patient developed hematuria again, and an MRI diagnosis revealed a locally invasive T4 bladder cancer that invaded the branch of the internal iliac artery that developed from the diverticulum
.

After surgery, it was found to be high-grade invasive urothelial carcinoma, and the patient refused total cystectomy and opted for bladder-sparing therapy
.

Figure 1.
Imaging and pathological findings after radiotherapy.
Chemotherapy with cisplatin and gemcitabine was administered first, followed by radiotherapy
.

However, residual tumor was still found after treatment, so the patient received a chemotherapy combination of methotrexate, vinblastine, epirubicin, and carboplatin, which is the second-line treatment regimen
.

But this regimen did not work, and the disease continued to progress rapidly, and the patient presented with pain and swelling in his left leg
.

It happened that Japan approved the PD-1 inhibitor pembrolizumab at this time, so the patient started treatment with pembrolizumab
.

After six courses of treatment, CT imaging showed that the tumor had shrunk by 50%, and the clinical assessment was a partial response
.

After nine courses of PD-1 inhibitor therapy, repeated flushing of the bladder was necessary due to repeated necrotic tissue that led to urinary retention
.

Due to the problem of urinary retention, the patient was treated for ureterocutaneous fistula without total bladder resection
.

After the operation, the necrotic tissue disappeared
.

After another six cycles of PD-1 inhibitor therapy, the tumor regressed completely
.

Clinical assessment was complete remission
.

After 20 courses of PD-1 inhibitors, the patient developed adverse reactions to immunotherapy such as ACTH (adrenocorticotropic hormone) deficiency and rash, so the patient stopped using pembrolizumab
.

Although the use of PD-1 inhibitors was stopped, the patient had achieved complete remission for more than 24 months, indicating a longer-term survival benefit
.

Figure 2.
Imaging and pathological results after PD-1 treatment.
Later researchers performed PD-L1 expression detection on tumor tissue biopsied from patients at different stages, and found that the PD-L1 expression of patients was negative at the beginning; in the stage of radiotherapy and chemotherapy , PD-L1 expression in tumor tissue samples of patients was positive, which was 5%; and PD-L1 expression exceeded 10% after radiotherapy and chemotherapy
.

Enlightenment Summarizing this treatment case, we found that the timing of this patient's use of PD-1 inhibitors was coincidental.
During the initial treatment, PD-1 inhibitors were not yet available in Japan, and the patient received two stages of chemotherapy successively.
The therapeutic effect Neither is ideal
.

After testing, the expression of PD-L1 in the initial tumor tissue of the patient was negative.
After the tumor cells were killed by early radiotherapy and chemotherapy, PD-L1 began to express
.

At this time, PD-1 inhibitors were launched in Japan, and patients started to use PD-1 inhibitors to take effect and achieved good therapeutic effects
.

When choosing a treatment method, many patients always mistakenly believe that the most advanced must be the best, which can quickly relieve or even cure their own pain
.

The traditional radiotherapy and chemotherapy, in the hearts of patients, not only have serious side effects, but also may not be effective, so they will subconsciously reject these treatments
.

However, there are great individual differences in the treatment of tumors.
Which treatment method to choose and which drugs can be used in combination need a professional doctor to make a decision based on the actual situation of the patient in order to achieve the best treatment effect
.

Haste is not enough.
At present, the treatment methods for many solid tumors are actually limited.
We must find a way to maximize the effect of each method and drug and maximize the benefits as much as possible
.

For more information about tumor treatment, please search and download the Cancer App
.

Reference: Yuki Horibe, et al.
, A case of long-term complete remission of locally advanced T4 bladder cancer treated with pembrolizumab.
Urology Case Reports 41 (2022) 101959.
Click below to learn more about cancer prevention in selected clinical trials Anti-cancer dry goods-swipe left and right to see more-