Prostate Cancer: Improving Patient Survival and Quality of Life
—For patients with biochemical recurrent prostate cancer, prostate-specific membrane antigen positron emission tomography has the potential to improve long-term outcomes. A new study tested this theory.
Mounting evidence supports the superior sensitivity and specificity of prostate-specific membrane antigen positron emission tomography (PSMA-PET) over conventional imaging for the detection of biochemical recurrent (BCR) prostate cancer,1-4 but little is known about how this shift in imaging affects outcomes for patients.1
According to Michael S. Leapman, MD, MHS, the corresponding author of a new study on this topic, it boils down to this: Does the use of PSMA-PET for earlier detection of recurrence lead to unnecessary overtreatment of a cancer that might never emerge clinically? Or, does it offer patients longer survival and better quality of life?
“In the absence of high-quality evidence to answer these crucial questions we designed a decision analytic modeling study to which we applied the best available evidence,” says Dr. Leapman, who is an associate professor of urology at Yale School of Medicine, in New Haven, Conn.
A comparison of 3 distinct treatment strategies
“In this model, we simulated the potential paths that a patient could take following a diagnosis of recurrent prostate cancer,” Dr. Leapman explained. “This involved developing a detailed framework to consider the potential outcomes that could occur through various imaging strategies, including up-front PSMA-PET; conventional imaging, such as CTBS [computed tomography and bone scan]; or conventional imaging followed by PSMA-PET if conventional imaging is negative.”
The model suggested that, assuming even modest benefits of earlier detection and treatment, imaging patients with BCR prostate cancer with PSMA-PET could reduce mortality and improve quality of life.1 Model estimates were based on 1000 simulated patients with BCR prostate cancer, with an assumed median age of 66 years.
The 3 strategies compared were immediate imaging with PSMA-PET alone; conventional imaging (CTBS) followed by PSMA-PET when findings were negative or equivocal; and CTBS alone.
Better disease detection with PSMA-PET
“Our findings suggested that PSMA-PET alone, or following negative or equivocal findings with CTBS, may be expected to detect more than double the number of patients with metastatic disease and lead to initiation of systemic treatment in more than 60% of patients imaged,” says Dr. Leapman.
Here are the specifics:
Projected detection of metastatic disease
- PSMA-PET alone: 611 patients (95% uncertainty interval [UI] 565 to 656 patients)
- Negative or equivocal findings on CTBS, followed by PSMA-PET: 630 patients (95% UI 586 to 675 patients)
- CTBS alone: 297 patients (95% UI 202 to 410 patients)
Projected detection of localized disease
- PSMA-PET alone: 140 patients (95% UI 109 to 177 patients)
- Negative or equivocal findings on CTBS, followed by PSMA-PET: 144 patients (95% UI 112 to 181 patients)
- CTBS alone: 10 patients (95% UI 2 to 25 patients)
Improved mortality and quality of life
“Our results estimated that PSMA-PET imaging strategies would result in nearly 1 additional year of life and 0.8 quality-adjusted life-years [QALYs] per patient,” says Dr. Leapman.
Here’s what he and his colleagues reported:
Estimated life-years
- PSMA-PET alone: 10,987 (95% UI 10,437 to 11,528)
- Negative or equivocal findings on CTBS, followed by PSMA-PET: 10,853 (95% UI 10,305 to 11,390)
- CTBS alone: 9999 (95% UI 9291 to 10,707)
Estimated QALYs
- PSMA-PET alone: 8741 (95% UI 8165 to 9289)
- Negative or equivocal findings on CTBS, followed by PSMA-PET: 8609 (95% UI 8043 to 9152)
- CTBS alone: 7917 (95% UI 7280 to 8591)
Estimated deaths from prostate cancer
- PSMA-PET alone: 512 (95% UI 472 to 552)
- Negative or equivocal findings on CTBS, followed by PSMA-PET: 520 (95% UI 480 to 559)
- CTBS alone: 587 (95% UI 538 to 632)
Does PSA level have any effect?
Yes, it does, the investigators say. They reported that prostate-specific antigen (PSA) level seemed to impact both detection and mortality/morbidity.
“The probability of detecting visible disease on PSMA-PET increased with a patient’s PSA level,” Dr. Leapman notes. “Based on differences in detection, the results from our simulation model suggest that there may be greatest incremental benefit for patients with higher PSA levels, such as those of 5 ng/mL or higher. However, additional study is needed to determine the conditions for which an individual would benefit most from earlier detection.”
“While patients with PSA levels greater than or equal to 5 ng/mL were estimated to accrue the greatest benefits in mortality and QALY, likely due to a lower prevalence of localized or metastatic disease at lower PSA levels, improved outcomes were still projected for patients with PSA levels less than 2 ng/mL,” he added.
Limitations and conclusions
The authors pointed out several limitations to their study. First, they noted that the randomized clinical trials relied on to support the model’s assumption that earlier detection of local or metastatic disease would lead to improved survival were done without PSMA-PET–based imaging definitions of metastasis and prior to changes in recommended chemotherapy regimens.
Additionally, input was based on retrospective studies that included patients with lower PSA levels, which means the results may not extrapolate to patients with very high PSA levels in whom detection of metastasis might be more likely with conventional imaging.
That said, “PSMA-PET imaging is becoming more widespread and is now covered by Medicare and most commercial insurers, but questions have remained regarding its impact on patient outcomes,” Dr. Leapman concluded. “Our model showed that even modest benefits associated with earlier detection offered by this imaging could improve survival and quality of life for patients with BCR prostate cancer.”
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