What is the prognosis for recurrent prostate cancer with a Gleason score of 4+3 following a radical prostatectomy (total prostate removal), and how is the prostate-specific antigen (PSA) doubling time evaluated?

From the Guidelines

The prognosis for recurrent prostate cancer with a 4+3 Gleason score following a total prostatectomy is generally guarded, with a 5-year systemic progression-free survival exceeding 93% in patients with PSA doubling times greater than 6 months, versus 64% for those with doubling times less than 6 months 1. To evaluate the doubling time of PSA, at least three consecutive PSA measurements taken at consistent intervals are required. The calculation involves dividing the natural log of 2 (0.693) by the slope of the relationship between the natural log of PSA and time in months. Many online calculators and medical software can perform this calculation automatically. Some key points to consider in the management of recurrent prostate cancer include:

• The importance of PSA doubling time in predicting disease progression, with slower doubling times associated with better outcomes 1
• The role of salvage radiation therapy, which is most effective when initiated early, ideally when PSA levels are below 0.5 ng/mL
• The consideration of androgen deprivation therapy, particularly in patients with high-risk disease or rapid PSA doubling times
• The need for regular monitoring with PSA tests every 3-6 months to track disease progression and adjust treatment plans accordingly
• The higher Gleason score (4+3) indicates more aggressive disease compared to a 3+4 score, as the primary pattern 4 suggests more poorly differentiated cancer cells. Recent guidelines, such as those from the National Comprehensive Cancer Network, recommend adjuvant radiation therapy after prostatectomy in men with adverse pathologic features, including positive margin, seminal vesicle invasion, and/or extracapsular extension 1. However, the management of recurrent prostate cancer should be individualized, taking into account the patient's overall health, disease characteristics, and personal preferences.

From the FDA Drug Label

The median PSADT was 4.9 months. Seventy-four percent (74%) of patients had prior definitive therapy with radical prostatectomy, 34% of patients had prior primary radiotherapy (including brachytherapy), and 49% of patients had prior therapy with both surgery and radiotherapy (including adjuvant and salvage radiotherapy). Thirty-two percent (32%) of patients had a Gleason score of ≥ 8 Patients were required to have confirmation of non-metastatic disease by BICR, high‑risk BCR (defined by a PSA doubling time ≤ 9 months), and PSA values ≥1 ng/mL if they had prior radical prostatectomy (with or without radiotherapy) as the primary treatment for prostate cancer or PSA values at least 2 ng/mL above the nadir if they had prior radiotherapy only

The prognosis for recurrent prostate cancer with a 4+3 Gleason score following a total prostatectomy is not directly stated in the label.

• Key points:
  • The label mentions that 32% of patients had a Gleason score of ≥ 8, but it does not provide specific information on the prognosis for a Gleason score of 4+3.
  • The label defines high-risk biochemical recurrence (BCR) as a PSA doubling time ≤ 9 months.
• PSA doubling time evaluation:
  • The label states that patients were required to have a PSA doubling time ≤ 9 months to be considered high-risk BCR.
  • The median PSADT was 4.9 months in the study population 2.

From the Research

Prognosis for Recurrent Prostate Cancer

• The prognosis for recurrent prostate cancer with a 4+3 Gleason score following a total prostatectomy is influenced by several factors, including the Gleason score, PSA level, and recurrence pattern 3.
• A higher Gleason score is associated with a poorer prognosis, and the 4+3 score is considered intermediate to high risk 4, 5, 6.
• The recurrence pattern is also important, with local recurrence in the prostatectomy bed only having a better prognosis than loco-regional metastases or distant metastases 3.

Evaluating Doubling Time of PSA

• The doubling time of PSA is an important factor in evaluating the prognosis of recurrent prostate cancer 3.
• A shorter PSA doubling time is associated with a poorer prognosis, while a longer doubling time is associated with a better prognosis 3.
• The PSA doubling time can be calculated using the formula: PSA doubling time = (ln(2) * time) / (ln(PSA2) - ln(PSA1)), where PSA1 and PSA2 are two consecutive PSA measurements, and time is the time interval between the two measurements.
• However, the provided studies do not specifically address the calculation of PSA doubling time, and further research is needed to determine the optimal method for evaluating PSA doubling time in the context of recurrent prostate cancer.

Gleason Score and Prognosis

• The Gleason score is a powerful predictor of cancer behavior and prognosis in prostate cancer patients 4, 5, 6.
• A higher Gleason score is associated with a poorer prognosis, and the 4+3 score is considered intermediate to high risk 4, 5, 6.
• The Gleason score can be used to predict the risk of biochemical failure, metastatic disease, and prostate cancer-related death 6.