BERKELEY, CA (UroToday.com) - The management of high-risk prostate cancer (HRPC) is becoming a top priority for improving prostate cancer (PCa) outcomes. There is still no consensus on a definition of high-risk prostate cancer at the moment. In 1998 d’Amico classified PCa patients according to PSA, Gleason grade, and clinical stage. However, the classification in only 3 risk groups and considering only 3 factors is probably insufficient. In this article we discuss the different classifications and updates in view of giving a more precise prediction of outcomes, especially the need for sub-stratification.
There has been a historical trend to treat HRPC with radiotherapy (RT) and/or androgen deprivation therapy (ADT), even in the absence of level 1-evidence to support it. On the other hand, many studies that we present here have proven the feasibility of RP in HRPC, and analysis of the SEER database concluded that the greatest benefit of RP over RT in CSS was in otherwise fit patients with HRPC.
The biggest issue in HRPC is the selection of patients for surgery, given the heterogeneity of their prognosis. Briganti has produced a nomogram to address this patient selection issue and predictably found that the presence of more than one high-risk factor was associated with a significantly lower rate of specimen confinement.
We discuss the controversial role of clinical staging in risk stratification. Most HRPC cases have extraprostatic disease, but the disease is organ-confined in 26-31% of the cases and those with specimen-confined pT3 disease have good biochemical and clinical PFS.[3, 4] It also seems that multiparametric MRI, and especially T2-weighted imaging, may be useful in staging selected patients with intermediate- to high-risk PCa.
This article also shows that RP is a reasonable option in Gleason 8-10 patients, even more taking into account that up to 45% are downgraded on prostatectomy specimen. Multiparametric MRI with DWI may have a role in detecting high-grade cancer as there seems to be a correlation of ADC with biopsy Gleason score.
It is well known that radical prostatectomy for clinical T3 disease requires some surgical expertise to keep the morbidity acceptable. We show evidence that minimally invasive surgery is gaining its space in HRPC, bringing reduced intra-operative blood loss and faster convalescence. Furthermore the decision to perform a nerve-sparing surgery (NSS) should be adapted to each patient and to each side of the prostate. Our LRP series has shown that overall PSM rate correlates with pathological T stage but is not influenced by NSS . Multiparametric MRI with DWI seems to have a role in reducing PSM caused by inadequate NSS by predicting extraprostatic extension.
In HRPC it is essential to perform an extended pelvic lymph node dissection (ePLND). Besides the known importance of high lymph node yield, we discuss the results from Briganti and Studer’s groups concluding that patients with 1-2 positive nodes on ePLND have significantly better long-term CSS than the ones with 3 or more.[7, 8] It is our belief that there will soon be enough evidence to change the TNM staging classification for prostate cancer in order to divide node-positive patients into N1 and N2 depending on the number of positive nodes, as they carry different prognosis.
When discussing surgery with a patient with HRPC, it should be made clear that a multimodality treatment may be required. In cases where the need for radiotherapy is extremely predictable, one might think that the patient should have primary RT. However a surgery-first approach to multimodal treatment may have advantages, as salvage radiotherapy following surgery is better tolerated than salvage surgery following radiotherapy.
In conclusion, HRPC comprises a very significant number of patients who seem to be the most likely to benefit from treatment in the long term. However this is a very heterogeneous group, given the multiple classifications and the high rates of downstaging and downgrading by the time of surgery. Outcomes are therefore not uniform and are difficult to interpret. RT is a treatment with proven value in high-risk localised and locally advanced PCa, but we now have strong evidence that surgery has also an important role in the management of HRPC. The biggest issue is to have the right criteria to select the patients most likely to benefit from a “surgery first” approach, always keeping in mind that a multimodal treatment may be needed.
- Joniau S, Briganti A, Gontero P, Gandaglia G, Tosco L, Fieuws S, et al. Stratification of High-risk Prostate Cancer into Prognostic Categories: A European Multi-institutional Study. Eur Urol 2014 Jan 25. pii: S0302-2838(14)00071-2. doi: 10.1016/j.eururo.2014.01.020
- Abdollah F, Schmitges J, Sun M, Jeldres C, Tian Z, et al. Comparison of mortality outcomes after radical prostatectomy versus radiotherapy in patients with localized prostate cancer: A population-based analysis. Int J Urol 2012; 19: 836-844
- Briganti A, Joniau S, Gontero P, Abdollah F, Passoni NM. Identifying the best candidate for radical prostatectomy among Patients with High-Risk Prostate Cancer. Eur Urol 2012; 61: 584-592
- Di Benedetto A, Soares R, Dovey Z, Bott S, McGregor RG, Eden CG. Laparoscopic radical prostatectomy for high-risk prostate cancer. BJU Int. 2014 May 6. doi: 10.1111/bju.12797
- Kitajima K, Takahashi S, Ueno Y, Miyake H, Fujisawa M, Kawakami F, et al. Do apparent diffusion coefficient (ADC) values obtained using high b-values with a 3-T MRI correlate better than a transrectal ultrasound (TRUS)-guided biopsy with true Gleason scores obtained from radical prostatectomy specimens for patients with prostate cancer? Eur J Radiol. 2013 Aug; 82(8): 1219-26.
- McClure TD, Margolis DJ, Reiter RE, Sayre JW, Thomas MA, Nagarajan R, et al. Use of MR imaging to determine preservation of the neurovascular bundles at robotic-assisted laparoscopic prostatectomy. Radiology. 2012 Mar; 262(3): 874-83.
- Bader P, Burkhard FC, Markwalder R, Studer U. Disease progression and survival of patients with positive lymph nodes after radical prostatectomy. Is there a chance of cure? J Urol 2003 Mar; 169(3): 849-54.
- Briganti A, Karnes JR, Da Pozzo LF, Cozzarini C, Gallina A, Suardi N, et al. Two positive nodes represent a significant cut-off value for cancer specific survival in patients with node positive prostate cancer. A new proposal based on a two-institution experience on 703 consecutive N+ patients treated with radical prostatectomy, extended pelvic lymph node dissection and adjuvant therapy. Eur Urol 2009 Feb; 55(2): 261-70.
- van der Poel HG, Moonen L, Horenblas S. Sequential treatment for recurrent localized prostate cancer. J Surg Oncol 2008; 97: 377-382
Conflicts of interest: none
R. Soares and C. G. Eden as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, United Kingdom