Introduction
There is a substantial number of men with prostate cancer that will never end up dying from the disease. This is the results of marked differences in the aggressiveness of the disease, with some cancers showing progression whilst others “lower risk” cancers hardly change over time.
This observation led to the development of active surveillance, in which we keep a close eye on patients with lower risk prostate cancer but only treat those patients that show progression to more higher risk prostate cancer. The main challenge is to detect those patients that show progression, and all our research in active surveillance is focussed on this.
This new treatment paradigm was developed as a response to complications seen after whole-gland treatment (treating the entire prostate) like surgery or radiotherapy. In order to be a candidate for a focal treatment, prostate cancer needs to be confined to one localized region within the prostate and be of intermediate aggressiveness.
Different techniques can be used to focally ‘ablate’ (treat) prostate cancer (freezing, laser, focussed ultrasound (heating) or electricity. We used irreversible electroporation as ablative modality, in which the tumour is killed by high-voltage electrical shocks between needles that surround the tumour. Our research line contains multiple projects on selection the appropriate patient for focal therapy, evaluation the outcomes of focal therapy and is looking to improve the outcomes and selection for this new modality.
What we’ve done so far
Multiple projects looked that what tissue characteristics could be identified that predict progression, using the biopsies or prostates after surgery of patients. We found that perineural invasion (growing close to nerve tissue) and the amount of positive biopsies (Quinn et al., 2003) were important. Likewise, the aggressiveness of the tissue is crucial (Rasiah et al., 2003) as well as the scoring system that’s being used (Grogan et al., 2017). We looked at the deciding factors for patients when choosing for active surveillance and showed that the surgeon or general practitioner's recommendation was the most influential factor (Bayliss, Duff, Stricker, & Walker, 2017).
The development of new biopsies techniques (transperineal template biopsies) allowed us to better diagnose patients with truly lower risk prostate cancer, improving the outcomes and inclusion of active surveillance (van Leeuwen et al., 2016), (Ting et al., 2015), (Thompson et al., 2015), (Symons et al., 2013), (Huo et al., 2012), (Hossack et al., 2012). We also looked with other to see how much survival gain might justify the risk for complications seen after treatment (King et al., 2012).
Ongoing projects
In an interim analysis of our MRI active surveillance study we have shown that we are able to safely reduce the need for prostate biopsies in the follow-up, without impacting the outcomes of patients (Amin et al., 2020). These data were also used in a bigger collaboration around the world, highlighting the importance of MRI results within active surveillance (Olivier et al., 2022). Our MRI active surveillance study now completed and the final results of the study will be published soon.
Future directions
In the recent years a new kind of scan has been developed, Prostate-Specific Membrane Antigen PET CT scan. We are currently running a study to evaluate its use in patients with active surveillance, aiming to further reduce the need for biopsies and to improve the detection of those patients that progress. Moreover, colleagues at the Garvan Institute are developing (epi)genetic markers that may better predict the presence or progression of prostate cancer outside the standard diagnostic pathway we nowadays use.
Our publications on active surveillance
Amin, A., Scheltema, M. J., Shnier, R., Blazevski, A., Moses, D., Cusick, T., … Thompson, J. (2020). The Magnetic Resonance Imaging in Active Surveillance (MRIAS) Trial: Use of Baseline Multiparametric Magnetic Resonance Imaging and Saturation Biopsy to Reduce the Frequency of Surveillance Prostate Biopsies. The Journal of Urology , 203 (5), 910–917. https://doi.org/10.1097/JU.0000000000000693
Bayliss, D. R., Duff, J., Stricker, P., & Walker, K. (2017). Decision-Making in Prostate Cancer – Choosing Active Surveillance Over Other Treatment Options: A Literature Review. Urologic Nursing , 37 (1), 15–22.
Grogan, J., Gupta, R., Mahon, K. L., Stricker, P. D., Haynes, A.-M., Delprado, W., … Kench, J. G. (2017). Predictive value of the 2014 International Society of Urological Pathology grading system for prostate cancer in patients undergoing radical prostatectomy with long-term follow-up. BJU International , 120 (5), 651–658. https://doi.org/10.1111/bju.13857
Hossack, T., Patel, M. I., Huo, A., Brenner, P., Yuen, C., Spernat, D., … Stricker, P. (2012). Location and pathological characteristics of cancers in radical prostatectomy specimens identified by transperineal biopsy compared to transrectal biopsy. The Journal of Urology , 188 (3), 781–785. https://doi.org/10.1016/j.juro.2012.05.006
Huo, A. S. Y., Hossack, T., Symons, J. L. P., PeBenito, R., Delprado, W. J., Brenner, P., & Stricker, P. D. (2012). Accuracy of primary systematic template guided transperineal biopsy of the prostate for locating prostate cancer: a comparison with radical prostatectomy specimens. The Journal of Urology , 187 (6), 2044–2049. https://doi.org/10.1016/j.juro.2012.01.066
King, M. T., Viney, R., Smith, D. P., Hossain, I., Street, D., Savage, E., … Armstrong, B. K. (2012). Survival gains needed to offset persistent adverse treatment effects in localised prostate cancer. British Journal of Cancer , 106 (4), 638–645. https://doi.org/10.1038/bjc.2011.552
Olivier, J., Li, W., Nieboer, D., Helleman, J., Roobol, M., Gnanapragasam, V., … Villers, A. (2022). Prostate Cancer Patients Under Active Surveillance with a Suspicious Magnetic Resonance Imaging Finding Are at Increased Risk of Needing Treatment: Results of the Movember Foundation’s Global Action Plan Prostate Cancer Active Surveillance (GAP3) Consort. European Urology Open Science , 35 , 59–67. https://doi.org/10.1016/j.euros.2021.11.006
Quinn, D. I., Henshall, S. M., Brenner, P. C., Kooner, R., Golovsky, D., O’Neill, G. F., … Stricker, P. D. (2003). Prognostic significance of preoperative factors in localized prostate carcinoma treated with radical prostatectomy: importance of percentage of biopsies that contain tumor and the presence of biopsy perineural invasion. Cancer , 97 (8), 1884–1893. https://doi.org/10.1002/cncr.11263
Rasiah, K. K., Stricker, P. D., Haynes, A.-M., Delprado, W., Turner, J. J., Golovsky, D., … Henshall, S. M. (2003). Prognostic significance of Gleason pattern in patients with Gleason score 7 prostate carcinoma. Cancer , 98 (12), 2560–2565. https://doi.org/10.1002/cncr.11850
Symons, J. L., Huo, A., Yuen, C. L., Haynes, A.-M., Matthews, J., Sutherland, R. L., … Stricker, P. D. (2013). Outcomes of transperineal template-guided prostate biopsy in 409 patients. BJU International , 112 (5), 585–593. https://doi.org/10.1111/j.1464-410X.2012.11657.x
Thompson, J. E., Hayen, A., Landau, A., Haynes, A.-M., Kalapara, A., Ischia, J., … Stricker, P. D. (2015). Medium-term oncological outcomes for extended vs saturation biopsy and transrectal vs transperineal biopsy in active surveillance for prostate cancer. BJU International , 115 (6), 884–891. https://doi.org/10.1111/bju.12858
Ting, F., van Leeuwen, P. J., Delprado, W., Haynes, A.-M., Brenner, P., & Stricker, P. D. (2015). Tumor volume in insignificant prostate cancer: Increasing the threshold is a safe approach to reduce over-treatment. The Prostate , 75 (15), 1768–1773. https://doi.org/10.1002/pros.23062
van Leeuwen, P. J., Siriwardana, A., Roobol, M., Ting, F., Nieboer, D., Thompson, J., … Stricker, P. (2016). Predicting Low-Risk Prostate Cancer from Transperineal Saturation Biopsies. Prostate Cancer , 2016 , 7105678. https://doi.org/10.1155/2016/7105678
Ongoing projects