Advice for Community Oncologists Treating Metastatic Castration-Resistant Prostate Cancer


Dr. Bobby Liaw looks to the future of metastatic castration-sensitive prostate cancer treatment and provides some advice and clinical pearls.

Bobby Liaw, MD: A lot is changing in the field of prostate cancer. Here are a couple of my thoughts on future directions and unmet needs. In terms of unmet needs, there still needs to be a little more focus on how we optimally sequence and combine the multiple drugs that we already have for prostate cancer. We’re already starting to see studies coming out for combination use. PEACE-1 data just started to come out and are showing that there may be a significant benefit to the combination of abiraterone and docetaxel in the upfront metastatic CSPC [castration-sensitive prostate cancer] setting. But we’re still waiting on data that will be coming out relatively soon from the ARASENS study, which is combining docetaxel with darolutamide, another oral AR [androgen receptor]-targeted drug. The data there are still pending, but that study is examining using a triplet regimen for upfront treatment of hormone-sensitive prostate cancer.

Outside of combinations, we’re also starting to see some of our “advanced drugs” that we used to reserve for castration-resistant prostate cancer make their way into localized disease. The recent STAMPEDE study is also showing improvement in outcomes when we combine abiraterone with hormone therapy, along with definitive curative-intent radiation therapy. We need to also expand our arsenal for people in the neoadjuvant and adjuvant settings, things that will perhaps intensify therapy to improve outcomes in patients undergoing definitive therapy. Certainly, more needs to be done in the metastatic setting.

PSMA [prostate-specific membrane antigen]-directed therapy is going to be very big. There’s going to be a very big push in developing more PSMA-directed therapy. We’re already anticipating the approval of Lutetium-177–PSMA-617, which is most likely to be approved in the castration-resistant prostate cancer setting, but there are ongoing studies to evaluate its use in the hormone-sensitive prostate cancer setting. We’re also engaging more in immunotherapy. PSMA-directed bispecific T-cell engagers are a very hot topic. We’re hoping that will add to our arsenal for people who have metastatic prostate cancer. And while there’s been a lot of movement in genomic sequencing of prostate cancer, trying to identify new genomic targets, as of right now, as part of standard options, we have PARP inhibitors for the group of patients who have homologous recombination repair deficiencies, but more needs to be done. Hopefully we’ll start to see more treatment options for all the other genomic abnormalities that we’re starting to find for prostate cancer.

There are a lot of key takeaways and clinical pearls. The prostate cancer landscape is constantly changing. As far as it’s come for metastatic hormone-sensitive prostate cancer, I’d say that combination therapy is now a standard of care. It’s really nice that we have many different options to choose from so that we can individualize the selection based on patient preference as well as disease presentation.

One thing that I’ll leave my colleagues with is that as we see many more of our therapeutic agents that were traditionally reserved for castration-resistant prostate cancer moving into hormone-sensitive and localized disease, it’s safe to say that’s a trend that’s here to stay. It’s going to be more important than ever for us to have a multidisciplinary approach to the treatment of our patients with prostate cancer. We may need to become more used to seeing patients who have much more localized disease, or even at the very beginning, when they’re starting to have biochemical recurrence, we’re starting to see that by being a little more thoughtful and a little more aggressive with our treatment therapy up front, we can really move the needle and improve patient disease control as well as disease outcomes in the long term.

Transcript edited for clarity.

Case: A 73-Year-Old Man With Biochemical Recurrence of Prostate Cancer and Metastatic Castration-sensitive High-volume Disease

January 2018

Initial Presentation

A 73-year-old man presents with urinary retention, fatigue and decreased appetite

Patient History, Lifestyle and Clinical workup

History of mild alcoholic liver cirrhosis

No family history of prostate cancer

Patient is active and is very involved in his grandchildren’s activities

TRUS and biopsy revealed adenocarcinoma of the prostate gland, Gleason score 8 [4+4] with disease in 10/12 cores.

PSA 150 ng/mL; Hb 9.7 g/dL; ANC 1.9

Liver function tests are abnormal

Initial Diagnosis and Treatment

Patient is diagnosed with localized prostate cancer

He undergoes robotic radical prostatectomy with subsequent PSA decrease (12 ng/mL)

CT and bone scans showed no residual disease

October 2019

Presentation at Recurrence

Patient complains of right hip pain and abdominal pain

Imaging with CT and bone scan showed multiple metastatic bone lesions in the pelvis and diffuse liver lesions

PSA 90 ng/mL; Hb 9.4 g/dL; ANC 1.5

Liver function tests continue to be abnormal

Diagnosis of Recurrence

Patient is diagnosed with biochemical recurrence of prostate cancer with high-volume castration-sensitive metastatic disease

Germline genetic testing is negative

Treatment for Recurrence

Patient wishes to receive oral treatment with good quality of life so he can continue to be involved in his grandchildren’s activities

Due to his abnormal liver function tests and desire to receive oral treatment, he is started on ADT + apalutamide

At his 1-year follow-up, the patient’s PSA remains undetectable

Follow-up imaging shows stable disease, and he continues to report a good quality of life

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