A Look Ahead at Prostate Cancer Management

As our understanding of prostate cancer continues to evolve, so does our approach to caring for our patients. Given the rapid pace of advancements in the diagnosis and treatment of prostate cancer, the greatest challenge may be coordinating these advances and applying them to disease management. Here are some areas where I believe the science is progressing and where it is shifting prostate cancer management.

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) examined the role of ¹⁷⁷Lu-PSMA-617 in extending imaging-based progression-free survival (PFS) and overall survival (OS) in the treatment of patients with PSMA PET-scan positive metastatic castrationresistant prostate cancer (mCRPC). Findings 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 benefi ts, the therapy plus standard of care also reduced the risk of worsening of health-related quality of life or worsening of pain intensity by more than half compared with the standard of care alone.¹ Patients with mCRPC typically experience complications from advanced disease,² and the promise of extended survival in PSMA-positive mCRPC, along with improved quality of life, makes the eventual approval of this therapy a signifi cant, and highly anticipated, development for the treatment of mCRPC.

What will this likely mean for the treatment of mCRPC? Could we see a move for this treatment earlier in the course of the disease? Based on the need and the demonstrated benefi ts, that is possible through defi nitive clinical trials currently underway. And with the rise of PSMA PET imaging for prostate cancer, we now have a diagnostic tool that can signifi cantly improve how we detect and assist in treatment of prostate cancer. The FDA-approved radioactive imaging agents, gallium (Ga) 68 PSMA-11 and fl uciclovine F18-labeled PSMA,³ can locate PSMA-positive lesions in men with prostate cancer and detect the spread of their cancer to other parts of the body more effectively compared with standard conventional imaging approaches. This targeted diagnostic has broader implications for the treatment of PSA biochemically recurrent disease.

Genomic Testing and Heterogeneity

The research community is getting smarter in terms of being able to see that all prostate cancer isn’t 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 it’s revealing is that prostate cancer is yet another disease that provides a lot of information for both germline and somatic mutations. For example, approaches that target DNA damage repair (DDR) pathways such as DDR/HRR gene alterations let us know if a patient may be eligible for PARP inhibitors, including olaparib (Lynparza) and rucaparib (Rubraca).4 Microsatellite instability-high (MSI-H) or mismatch repair defi ciencies (dMMR) may indicate that immunotherapy is the best approach to care.5 What we are fi nding is that, as we extend testing to more patients and biopsy tumors in mCRPC, there can be variant histologies in prostate cancer. The new framework of prostate cancer is that it’s a heterogenous disease. These complex patients require a more coordinated approach in these challenging clinical scenarios.

Multidisciplinary Care

Taken together, the PSMA evolution, genomic testing, and the heterogeneity of the disease, prostate cancer is clearly a disease that benefi ts from multidisciplinary care.

By the very complex nature of the disease, it is almost becoming a necessity that patients have at least 3 pillars of care: urology, medical oncology, and radiation oncology as a backbone of treatment options, with radiology and pathologic prostate expertise playing an increasingly essential role. When you can achieve this level of multidisciplinary care, where you have different perspectives and different backgrounds of subspecialty care, there is a higher degree of confi dence that the patient is truly in the best hands.

This level of care is more typical in an academic center, but in a community setting, multidisciplinary care is achievable with virtual tumor boards and coordinated navigation though perhaps a little more complex if not under 1 roof.

Patients with prostate cancer can have more hope than ever. They have diagnostic testing that offers the promise of catching disease earlier and with greater specifi city, and they have more treatment options available to them, treatments that are more effective and with less toxicity.

_REFERENCES:

_{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 selection and determine progression in metastatic castration-resistant prostate cancer: expert opinion and review of the evidence. Can Urol Assoc J. 2018;12(9):E415-E420. doi:10.5489/cuaj.5154}

_{3. PSMA PET-CT accurately detects prostate cancer spread, trial shows. News 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 on-going 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 a perspective on resistance mechanisms. Br J Cancer. 2019;121(10):809-818. doi:10.1038/s41416-019-0599-y}