# Chemotherapy-Forward Management of Advanced Prostate Cancer: Taxane Timing, Sequencing and the Real-World Place of Immunotherapy

## TL;DR

This paper reviews how chemotherapy and immunotherapy are used in advanced prostate cancer, focusing on timing, patient selection, and treatment strategies.

## Contribution

The paper provides a practical framework for integrating taxane chemotherapy and immunotherapy in advanced prostate cancer treatment.

## Key findings

- Early docetaxel in metastatic castration-sensitive prostate cancer improves outcomes in fit patients with high disease burden.
- Cabazitaxel is preferred over ARPI switching in metastatic castration-resistant prostate cancer after prior docetaxel.
- Immunotherapy has limited benefit but is important for specific biomarker-defined subsets of prostate cancer patients.

## Abstract

Treatment for metastatic prostate cancer has changed rapidly. Chemotherapy is no longer reserved for the end of the disease course: using the docetaxel earlier can improve survival for selected patients, and later chemotherapy can regain control when resistance to hormone-targeted drugs develops. This review provides a practical, clinic-ready framework for deciding when to use docetaxel and the second-generation taxane cabazitaxel, how to select patients based on disease burden, pace of progression, symptoms, and overall fitness, and how to deliver treatment safely with proactive supportive care. We also clarify where immunotherapy fits today. For most patients, checkpoint inhibitors have limited benefit, but they are important for specific biomarker-defined tumors, and cellular immunotherapy may help selected men with low symptom burden. Finally, we summarize ongoing trials and emerging antigen-directed immune platforms that may expand the role of immunotherapy in defined subsets.

Taxane chemotherapy remains a durable backbone in advanced prostate cancer, but its clinical value is increasingly determined by timing, sequencing, and deliverability. We synthesize pivotal randomized trials and contemporary guidance to provide a chemotherapy-forward framework spanning metastatic castration-sensitive prostate cancer (mCSPC) and metastatic castration-resistant prostate cancer (mCRPC). In mCSPC, early docetaxel added to androgen deprivation therapy—often as part of triplet intensification with an androgen receptor pathway inhibitor (ARPI)—offers the greatest absolute benefit in fit patients with high disease burden or aggressive clinical tempo. In mCRPC, docetaxel remains foundational, while cabazitaxel is preferred over ARPI switching after prior docetaxel and one ARPI, supporting mechanism-based sequencing. Practical implementation requires proactive toxicity prevention (especially neutropenia), dose and schedule individualization, and preservation of functional status to maintain eligibility for subsequent life-prolonging therapies. Immunotherapy has a limited but important niche: sipuleucel-T may benefit selected patients with low symptom burden, whereas immune checkpoint inhibitors are best reserved for biomarker-defined subsets such as microsatellite instability-high or mismatch repair-deficient tumors; tumor mutational burden should be interpreted cautiously in prostate cancer. Ongoing trials and emerging antigen-directed platforms will clarify whether chemotherapy can act as an immune-enabling partner in defined settings.