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Typical Presentations of Metastatic Prostate Cancer and Risk of Disease Progression


Dr Neal Shore gives his first impressions of a patient case and gauges the risk of progression.

Case Overview:

Initial Presentation (Jan 2017)

A 64-year-old man is found to have a firm bilateral prostate nodule of 1.8 mm on his routine physical exam

Clinical workup

PSA 109.1 ng/mL

Family history of prostate cancer (father, uncle)

Transrectal ultrasound (TRUS)-guided biopsy of the prostate confirms advanced adenocarcinoma of the prostate and Gleason score of 8 (4 + 4)/Grade Group 4

MRI is negative for pelvic LN involvement but positive for one 1.1-cm mediastinal supraclavicular LN (T2bN0M1a)

His ECOG PS is 1

Germline multigene testing of biopsy specimen revealed a BRCA2 mutation

Initial Treatment (starting Feb 2017)

Patient was started on leuprolide and abiraterone; scheduled for physical exam, PSA assessment, and imaging every 3 months.

By the second follow-up visit (6 months after initiating treatment; August 2017), PSA levels declined to 2.1 ng/mL and prostate nodule size was 1.4 mm.

Patient’s disease remained stable through August 2018 (18 months of treatment).

21- and 24-month Follow-up Notes (November 2018, February 2019)

Patient’s PSA levels increased to 46.9 ng/mL in 11/2018 and 73.7 ng/mL in 2/2019.

MRI revealed that the size of the existing positive LN increased to 1.3 cm, and revealed a new, faintly positive 0.9-cm para-aortic LN.

Given the recent findings and the patient’s known BRCA2 mutation status, the patient and clinician decide to initiate olaparib 300 mg BID.

Neal Shore, MD, FACS: First, is this case representative of a typical patient I might see? The answer is yes. With the decrease of regular PSA [prostate-specific antigen] screening, we’re seeing more patients in the United States, and I think in other parts of the world as well. Historically we’ve seen high initial presentations in areas of the world where there’s never been a lot of prostate cancer screening, a very high percentage of patients who present with low- to high-volume metastatic castration-sensitive prostate cancer. And so, this is absolutely a patient I see regularly, monthly if not weekly, within my clinic. It seems more times than not they present asymptomatically. It’s either being picked up by a PSA or an abnormal DRE [digital rectal exam]. Or maybe there are some subtle symptomatic changes, or sometimes not so subtle: bone pain, loss of weight, inanition. Or there’s a CT scan obtained for some other reason and it incidentally finds a bone lesion or lymphadenopathy, occasionally liver metastases or pulmonary metastases.

Are there any risk factors that might put a patient at a higher risk of progression? I think in this patient’s case, we know that the grade group score, the higher the number, certainly the grade groups 4 and 5, is indicative of more aggressive biology. The fact that his PSA was so high, and also the fact that the patient has a BRCA [gene mutation]. We do have data that say that patients even with localized disease, who don’t have metastatic disease, there have been studies to demonstrate that patients with BRCA, particularly BRCA2, may progress a little more quickly, may get upgraded earlier to higher-grade pathology with subsequent biopsies for those patients who are doing active surveillance. Typically, if I have a patient who is grade group 1 or 2, who’s BRCA, I’m going to follow him a bit more vigilantly than someone who is not BRCA- or HRR [homologous recombination repair]-mutation positive. The fact that he also has a palpable nodule, a positive DRE, is certainly an increased risk of likely progression as opposed to a T1c incidental finding of a positive adenocarcinoma just based upon a PSA.

In my practice, how many patients with metastatic prostate cancer have progression to CRPC [castration-resistant prostate cancer] on and after ADT [androgen deprivation therapy] for HSPC [hormone-sensitive prostate cancer]? The answer is really 100%, unless they succumb to their disease while they’re still castration sensitive or succumb to some other comorbidity. So frankly, starting ADT is the foundational treatment, as we like to say. It’s going all the way back to [Charles] Huggins and [Clarence] Hodges. But unfortunately, it is not curative. There are always the rare exceptions, and some of us have seen those patients. But I think it’s fair to say that 99% of the time, when you start someone on testosterone suppression, regardless of whether it’s an agonist or an antagonist, whether you do combination therapy with an AR [androgen receptor] pathway drug, or docetaxel, or even arguably triplet therapy, that undoubtedly if the patients don’t succumb to something other than their prostate cancer, such as a cardiovascular event or a motor vehicle accident, they will all convert to resistant disease. That’s sort of the bane of existence of our lines of treatment. We know that resistance is coming, and so much of our clinical trial and preclinical work and the great work by many of our bench scientists is looking at alternative targets to overcome that resistance and/or combine other therapies to our existing therapies to lessen or diminish the onset of resistance.

Transcript edited for clarity.

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