We led a multi-institutional observational study supported by the EAU-YAU Prostate Cancer Working Group aimed at determining the long-term oncologic outcomes of patients with GG1 prostate cancer followed by active surveillance according to their type of diagnosis: incidental or on biopsy.3 A total of 2113 patients, of which 213 had incidental prostate cancer were evaluated using competing risk regression analyses.
At first, we observed that patients with incidental cancers were followed less intensively than those diagnosed on biopsy. The incidence of follow-up biopsies was approximately 10% lower during time for patients with incidental cancers.
Secondly, rates of treatment were lower at ten years for patients with incidental cancer (22%) vs. biopsy (53%). On the other hand, we observed a much higher incidence of de-intensification, meaning that patients were moved to a strategy encompassing follow-up with PSA only rather than multiparametric MRIs and biopsies, in patients with incidental cancers (29% vs. 6.5%), as shown in the Figure. In terms of metastases, the incidence was low in both groups, with an estimated 65% lower incidence in patients with incidental cancer, with however large confidence intervals and no statistical significance.
Figure: Cumulative incidence of long-term active surveillance events. The dashed lines represent treatment, the solid lines represent de-intensification. Patients diagnosed on biopsy are displayed in black, and those with incidental cancer in orange.
At last, we explored the risk of GG≥2 on the first follow-up biopsy, which was lower for incidental cancers compared to biopsy (7% vs 22%). We underline that such risk derived from our selected population (i.e., those with incidental cancers initially managed with active surveillance) is likely lower than the true prevalence of higher-grade cancer in patients with incidental prostate cancer.
Our findings open to the need for further research in the field of incidental low-grade prostate cancer. Given the low risk of GG≥2 on the first biopsy, although derived from an exploratory analysis, it is plausible that not all patients with incidental GG1 would benefit from active surveillance in the long term, especially those where initial follow-up biopsies show no cancer. Such a finding is primarily supported by the low incidence of further treatment and the high incidence of de-intensification in patients with incidental cancer. This means that many of them could theoretically undergo an initial workup to rule out aggressive disease and then be only monitored according to biopsy results. In other words, active surveillance appears appropriate only if GG1 is confirmed on the first biopsy. Another study using population-based data highlighted that even patients with incidental GG1 can have high disease-specific mortality if GG≥2 is found on a subsequent biopsy, supporting the need for further assessment if GG1 is discovered incidentally.4 Therefore, the focus of research should in our opinion rely on how patients with GG1 incidental prostate cancer should be initially managed to rule out aggressive prostate cancer. The main areas of research should be how to optimize multiparametric MRI during follow-up, and which patients could safely avoid further biopsies. Another unexplored area of interest is that of patients who underwent a workup excluding aggressive disease prior to the urinary obstruction procedure and then were diagnosed with incidental GG1. Such patients are probably at an even lower risk of developing further higher-grade prostate cancer and may theoretically avoid any of the postoperative workup, however, this needs to be further explored.
Written by: Riccardo Leni, MD & Giorgio Gandaglia, MD, FEBU
Division of Experimental Oncology, Department of Urology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
References:
- Cornford P, van den Bergh RCN, Briers E, Van den Broeck T, Brunckhorst O, Darraugh J, et al. EAU-EANM-ESTRO-ESUR-ISUP-SIOG Guidelines on Prostate Cancer—2024 Update. Part I: Screening, Diagnosis, and Local Treatment with Curative Intent. Eur Urol 2024.
- Capitanio U, Autorino R, Bandini M, Briganti A, Cheng L, Cooperberg MR, et al. Incidental Prostate Cancer (cT1a–cT1b) Is a Relevant Clinical and Research Entity and Should Be Fully Discussed in the International Prostate Cancer Guidelines. Eur Urol Oncol 2022;5:256–8.
- Leni R, Vertosick EA, van den Bergh RCN, Soeterik TFW, Heetman JG, van Melick HHE, et al. Oncologic Outcomes of Incidental Versus Biopsy-diagnosed Grade Group 1 Prostate Cancer: A Multi-institutional Study. Eur Urol Open Sci 2024;68:10–7.
- Leni R, Vickers AJ, Brasso K, Montorsi F, Briganti A, Nielsen TK, et al. Management and oncologic outcomes of incidental prostate cancer after transurethral resection of the prostate in Denmark. Journal of Urology 2024.