Given the rapid pace of progress in the diagnosis and treatment of prostate cancer, the biggest challenge may be coordinating these advances and applying them to the management of the disease.
As our understanding of prostate cancer continues to evolve, so does our approach to caring for our patients. Given the rapid pace of progress in the diagnosis and treatment of prostate cancer, the biggest challenge may be coordinating these advances and applying them to the management of the disease. Here are some areas where I believe science is advancing and changing the management of prostate cancer.
PSMA (prostate specific membrane antigen)
One of the most exciting and recent developments in the treatment of prostate cancer is Lutetium-177–PSMA-617 (177Lu-PSMA-617), a radioligand therapy that delivers beta-particle radiation to PSMA-expressing cells and the surrounding microenvironment.1 The Phase 3 VISION trial (NCT03511664) investigated the role of 177Lu-PSMA-617 in Extending Imaging-Based Progression-Free Survival (PFS) and Overall Survival (OS) in the Treatment of Patients With Metastatic Castration-Resistant Prostate Cancer (mCRPC) ) PSMA PET-scan positive. The results revealed that therapy with 177Lu-PSMA-617 Prolonged Imaging-Based PFS and OS When Added to Standard of Care in Patients With Advanced PSMA-Positive mCRPC Following Androgen Receptor Targeted Therapy and Chemotherapy .1 Beyond survival benefits, therapy combined with standard treatment also reduced the risk of worsening health-related quality of life or worsening pain intensity by more than half compared to to standard therapy alone.¹ Patients with mCRPC typically experience complications of disease,2 and the promise of prolonged survival in PSMA-positive mCRPC, as well as improved quality of life, make the eventual approval of this therapy an important and highly anticipated development for the treatment of mCRPC.
What will this likely mean for the treatment of mCRPC? Could we see a move towards this treatment earlier in the course of the disease? Based on demonstrated need and benefit, this is possible through definitive clinical trials currently underway. And with the rise of PET PSMA imaging for prostate cancer, we now have a diagnostic tool that can dramatically improve the way we detect and help treat prostate cancer. The FDA-approved radioactive imaging agents gallium (Ga) 68 PSMA-11 and fl uciclovin F18-labeled PSMA,3 can locate PSMA-positive lesions in men with prostate cancer and more effectively detect the spread of their cancer to other parts of the body compared to standard conventional imaging approaches. This targeted diagnosis has broader implications for the treatment of recurrent biochemical PSA disease.
Genomic testing and heterogeneity
The research community is getting smarter and smarter to be able to see that not all prostate cancers are the same. Genomic testing and sequencing have become the standard of care for high-risk patients with localized disease and patients with metastatic disease, and what they reveal is that prostate cancer is another disease that provides a lot of information about germline and somatic mutations. For example, approaches that target DNA damage repair (DDR) pathways such as DDR/HRR gene alterations allow us to know if a patient may be eligible for PARP inhibitors, including olaparib ( Lynparza) and rucaparib (Rubraca).4 Elevated microsatellite instability (MSI-H) or mismatch repair deficits (dMMR) may indicate that immunotherapy is the best approach to care. in prostate cancer. The new framework for prostate cancer is that it is a heterogeneous disease. These complex patients require a more coordinated approach in these challenging clinical scenarios.
Taken together, the evolution of the PSMA, the genomic tests and the heterogeneity of the disease, prostate cancer is clearly a disease that benefi ts from multidisciplinary management.
Due to the very complex nature of the disease, it becomes almost a necessity that patients have at least 3 pillars of care: urology, medical oncology and radiation oncology as the backbone of treatment options, expertise in radiology and prostate pathology playing an increasingly essential role. role. When you can achieve that level of multidisciplinary care, where you have different perspectives and different histories of superspecialized care, there’s a higher degree of confidence that the patient is truly in good hands.
This level of care is more typical in an academic center, but in a community setting, multidisciplinary care is achievable with virtual tumor charts and coordinated navigation, although perhaps a bit more complex if not under one roof.
Prostate cancer patients may have more hope than ever. They have diagnostic tests that promise to detect the disease earlier and with greater specificity, and they have more treatment options available to them, more effective and less toxic treatments.
1. Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for metastatic castration-resistant prostate cancer. N Engl J Med. 2021;385(12):1091-1103. doi:10.1056/NEJMoa2107322
2. Saad F, Pouliot F, Danielson B, Catton C, Kapoor A. Symptom assessment to guide treatment choice and determine progression of metastatic castration-resistant prostate cancer: expert opinion and evidence review . Can Urol Assoc J. 2018;12(9):E415-E420. doi:10.5489/cuaj.5154
3. PET-CT PSMA accurately detects the spread of prostate cancer, according to testing. Press release. National Cancer Institute. May 11, 2020. Accessed February 9, 2022. https://bit.ly/34rLcpl
4. Antonarakis ES, Gomella LG, Petrylak DP. When and how to use PARK inhibitors in prostate cancer: a systematic review of the literature with an update on ongoing trials. Eur Urol Oncol. 2020;3(5):594-611. doi:10.1016/j.euo.2020.07.005
5. Sahin IH, Akce M, Alese O, et al. Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and perspective on resistance mechanisms. Br J Cancer. 2019;121(10):809-818. doi:10.1038/s41416-019-0599-y