Patients with a detectable prostate-specific antigen (PSA) after radical prostatectomy (RP) may have excellent long-term outcomes, according to two retrospective studies conducted by UCSF researchers. The findings can help physicians provide more personalized recommendations for the type and timing of additional treatment for patients with biochemical recurrence of prostate cancer following RP.
“These studies describe the natural history of biochemical recurrence,” said UCSF urologic cancer surgeon Peter Carroll, MD, MPH, who led the studies. “We found that the spectrum of disease when it’s recurrent is similar to the spectrum of disease when patients first present. This information allows us to take a more nuanced approach to the management of patients with detectable PSA and gives patients and clinicians some real-world perspective.”
Not everyone with detectable PSA requires treatment
For the two studies, the researchers performed a retrospective analysis of patients who underwent RP for nonmetastatic prostate cancer at UCSF from 2000 to 2020. One study focused on patients with immediately detectable PSA, defined as greater than or equal to 0.03 ng/mL within six months of RP. The other study looked at patients with delayed detectable PSA, defined as two consecutive PSA results of greater than or equal to 0.03 ng/mL starting six months after surgery.
“Biochemical recurrence is frequently defined as a cut point of 0.2,” Carroll said. “The assays we’re using in contemporary studies are much more sensitive and are increasingly becoming more widely available to patients. I think, with time, the operational definition of biochemical recurrence as an actionable cut point will change.”
The researchers analyzed the risks of salvage therapy, metastasis-free survival (MFS), prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM). In addition to detectable PSA, variables included length of time to detectable PSA, Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score, PSA doubling time and genomic classifier.
Within 10 years of RP, the immediate versus delayed PSA groups differed in the receipt of salvage therapy (81% vs. 46%), as well as ACM (11% vs. 6%), PCSM (6% vs. 3%) and MFS (79% vs. 92%). A high Decipher genomic classifier score, increasing CAPRA-S score, and PSA doubling time of less than six months were associated with a greater likelihood of receiving salvage treatment.
“These results give patients hope that if PSA becomes detectable, the outcome is still likely to be quite good,” Carroll said. “Not everyone with detectable PSA requires immediate treatment. It’s important to consider cancer stage and grade at the time of diagnosis, time to recurrence, PSA kinetics and other relevant factors. The last five years have seen the emergence of molecular diagnostics and molecular imaging. These provide a risk profile and can help to predict outcomes. This information helps us risk stratify and offer treatment selectively to those who might benefit from it.”
New data lead to more personalized treatment recommendations
Carroll was integral to the research that led to the Food and Drug Administration’s approval of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging, a revolutionary new diagnostic method that can detect prostate cancer cells that have spread to lymph nodes both inside and outside the pelvis. The use of PSMA PET enables very precise cancer staging, which helps to guide treatment decisions.
“Before PSMA PET was available, it was difficult to localize recurrent disease,” Carroll said. “PSMA PET results have shown that prostate cancer is a much more complex disease than previously thought, completely different than the concept we had 15 or 20 years ago. Now the treatment approach is often based on the ability to localize the disease.”
The CAPRA scoring system was also developed at UCSF and serves as a straightforward, accurate instrument for facilitating disease risk classification in research and clinical decision-making.
“All this data gives us more information and insight on which to base any treatment or surveillance recommendations,” Carroll said. “At UCSF, we thrive on data. We measure outcomes to improve quality and benefit our patients. When a patient comes to UCSF for treatment, we can tell that person what to expect based on our data. We owe that to our patients and ourselves.”
Cancer research and treatment take place within the UCSF Helen Diller Family Comprehensive Cancer Center.
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