Despite their size, small cell carcinomas are aggressive cancers that have a high chance of metastasis. Doctors typically treat patients with chemotherapies, but relapses are common. However, the field recently saw some progress in small cell lung cancer, in particular. In a Phase 3 clinical trial, researchers combined chemotherapy with immunotherapy — specifically, the immune checkpoint inhibitor atezolizumab — which led to an increase in overall survival (1).
Inspired by similarities between small cell carcinomas in the lung, bladder, and prostate, Arnold Chin, a urologist at the University of California, Los Angeles, wondered if an immunotherapy and chemotherapy combination might also be effective in treating small cell bladder cancer and small cell/neuroendocrine prostate cancer. Treatment approaches for these cancers typically include platinum-based chemotherapy and localized treatment such as radiotherapy.
“Historically, small cell bladder cancer has followed small cell lung cancer treatments,” he said.

Arnold Chin studies the tumor microenvironment and cancer stem cell differentiation.
Credit: Broad Stem Cell Research Center
Chin and his team conducted a Phase 1b study of pembrolizumab (Keytruda) with platinum-based chemotherapy in 15 patients across two cohorts (2). Pembrolizumab is an immune checkpoint inhibitor, which helps T cells better recognize and attack cancer cells by blocking the PD-1 receptor on the T cell surface.
The research team administered the combination therapy to seven patients who had advanced or metastatic small cell bladder cancer and eight patients with small cell/neuroendocrine prostate cancer. The patients received the drugs for two years. Following the end of drug treatment, the researchers tracked whether disease progressed over time, finding that 86 percent of those with small cell bladder cancer had progression-free survival after two years and 14 percent of participants with small cell/neuroendocrine prostate cancer did. This result was an improvement over progression-free survival metrics for patients from historic data.
When the team looked at the median overall survival data — the length of time half of the patients in the trial are still alive — they saw that their results exceeded that of previous treatments. For metastatic small cell/neuroendocrine prostate cancer, their cohort had a median overall survival of 27 months, which is an improvement over the previous standard of seven to nine months. For small cell bladder cancer, the results look even better in that previous median survival was seven to 13 months, and at the time of data collection, the researchers had not yet reached the median overall survival point in the trial yet, meaning that more than half of the patients in the cohort were still alive.
"These activities seen with this combination absolutely are promising,” said Pedro Barata, a medical oncologist at University Hospitals who was not involved in the study. “If this data is proven in a large setting, [like] a larger data set, it could potentially become a new standard of care for these tumors.”
Historically, small cell bladder cancer has followed small cell lung cancer treatments.
- Arnold Chin, University of California, Los Angeles
Past studies of various cancer types have reported that clonal expansion of CD8+ T cells in the blood after treatment correlates with better progression-free survival (3). So, during the trial, the researchers sampled participants’ peripheral blood at three different time points. Chin and his team found that clonal expansion of CD8+ T cells in the samples from the study cohort correlated with overall progression-free survival. These T cells also had gene expression patterns that indicated a more activated state compared to those that did not expand.
“That signature was present even prior to treatment,” said Chin. So, could a blood test help predict whether combination therapy would be useful for a specific patient based on their T cells? “It's too early to say, based on the results of our study, but we're certainly looking into what we can obtain from this ‘liquid biopsy’ prior to therapy,” said Chin.
Barata added, “It’s promising. I do think these alterations at the cellular level can be used in [the] future as a biomarker.”
While Phase 1 clinical trials are small and holding a larger trial for such a rare disease is difficult, Chin is excited about the results from the combination therapy so far. “It was very rewarding that we saw really exceptional responses in several individual patients.”
References
- Horn, L. et al. First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer. N Engl J Med 379, 2220–2229 (2018).
- Gu, Y. et al. PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers. Cell Rep Med 5, 101824 (2024).
- Wu, T.D. et al. Peripheral T cell expansion predicts tumour infiltration and clinical response. Nature 579, 274-278 (2020).