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APCCC 2019: Local Treatment of The Primary (Surgery) in the Metastatic Situation

Basel, Switzerland (UroToday.com) Dr. Thomas Steuber spoke on the role of surgery in the setting of metastatic prostate cancer. Treatment of the primary tumor is considered standard of care in other malignancies (colorectal and ovarian for example). There are certain advantages specifically in surgical removal of the primary tumor. For instance, removing the prostate may prevent local complications, such as urinary obstruction, hematuria, and rectal stenosis. Removal of the primary tumor may also prevent further seeding from an uncontrolled primary tumor and may destroy cells with potential genetic instability.

Both the HORRAD and STAMPEDE trials demonstrated an overall survival benefit in similar patient populations,1,2 with low-volume metastatic disease, who received radiotherapy in addition to androgen deprivation therapy (ADT). Therefore, ADT alone is no longer a valid choice in this unique patient population. This recommendation has now been incorporated in the European guidelines, which state that castration combined with prostate radiotherapy should be offered to patients whose first presentation is M1 disease, and who have low volume of disease according to the CHAARTED criteria.

Although surgery may be effective in the same way as radiotherapy, radiotherapy might be effective via other mechanisms, such as immune modulation, so the role of surgery remains unproven and needs to be validated in the upcoming trials such as the TRoMbone trial, which has finished accruing patients in the UK. The TRoMbone is a randomized trial assessing radical prostatectomy in men with prostate cancer and oligometastases to the bone.

A previously published multicenter study assessing the perioperative outcomes of 106 patients who underwent radical prostatectomy for distant metastatic prostate cancer at presentation, showed that cytoreductive prostatectomy was feasible and comparable to surgery for high-risk prostate cancer patients.3 In the TRoMbone trial, there is a reported 8% rate of Clavien grade 3-4 complications, which is like the British Association of Urologic Surgeons (BAUS) average for high-risk prostate cancer. It has also been reported that the quality of life was better for patients who underwent surgery + androgen deprivation therapy (ADT) compared to those who received ADT alone, in theTRoMbone trial.

The local complication rate in patients with metastatic prostate cancer has been reported to be as high as 55% of patients. These include bleeding, obstruction, urinary retention, hydronephrosis, rectal stenosis, and pain. A previously published multicenter study including 263 metastatic castrate-resistant prostate cancer (mCRPC) patients, compared patients who received standard systemic therapy to those who received systemic therapy and palliative local therapy to the primary tumor with either surgery or radiotherapy.4 This study showed that the local complication rate was 20% in those treated with surgery, 47% for those treated with radiotherapy, and 55% for those not receiving local therapy, p=0.001.

Retrospective studies from the US SEER database and from the Munich Tumor registry have shown that cytoreductive prostatectomy confers an improved overall survival rate as well.5,6 There is also data showing that this type of treatment confers a cancer-specific survival advantage.7,8 In a recently published review, the overall survival and cancer-specific survival benefit of radical prostatectomy in metastatic prostate cancer patients were very clear (Figure 1). There are currently several prospective ongoing trials assessing the role of surgery in this unique metastatic setting (Table 1) which will be able to give us level one evidence regarding this specific question.

Figure 1 –Forest plot showing the effect of surgery on cancer-specific survival and overall survival compared with no local treatment in the setting of de novo metastatic prostate cancer:

APCCC_forest_plot.png

Table 1 – Prospective studies assessing the role of cytoreductive prostatectomy and overall survival:

APCCC_cytoreductive.png

The g-RAMPP study was a German multicenter prospective randomized study evaluating the effect of best systemic therapy with or without radical prostatectomy in men with limited bone metastatic disease. The inclusion criteria included not more than 5 bone metastatic lesions (according to conventional imaging – CT and bone scan), PSA less than 200 ng/ml, asymptomatic patients with locally resectable disease (less than clinical stage T3), ECOG performance status of 0-1, and patient age between 18 and 75. Unfortunately, the accrual rate was much lower than expected and the trial was closed prematurely.

Dr. Steuber concluded his talk summarizing that cytoreductive prostatectomy is feasible, with similar side effects compared to that seen in localized high-risk disease but should be restricted to high volume surgeons. Cytoreductive prostatectomy enables local control and improves quality of life. There is an overall survival benefit that was seen in retrospective studies, mainly from large population-based registries. Although not currently supported by the guidelines, Dr. Steuber believes cytoreductive prostatectomy should be offered to patients who are not suitable candidates for radiotherapy (patients with lower urinary tract symptoms). The results of the ongoing prospective trials are eagerly awaited to validate the reported benefit in previous retrospective studies.

Presented by: Thomas Steuber, MD, Martini Clinic Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany

Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA @GoldbergHanan at the 2019  Advanced Prostate Cancer Consensus Conference (APCCC) #APCCC19, Aug 29 - 31, 2019 in Basel, Switzerland

References:
  1. Parker CC et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. The Lancet. 2018. DOI: https://doi.org/10.1016/S0140-6736(18)32486-3
  2. Boeve LMS et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. European Urology. 2019;75(3):410-418. doi: 10.1016/j.eururo.2018.09.008.
  3. Sooriakumaran P et al. A Multi-institutional Analysis of Perioperative Outcomes in 106 Men Who Underwent Radical Prostatectomy for Distant Metastatic Prostate Cancer at Presentation. European Urology. 2016 May;69(5):788-94. doi: 10.1016/j.eururo.2015.05.023. 
  4. Won ACM et al. BJUI 2013
  5. Gratzke et al. Role of radical prostatectomy in metastatic prostate cancer: data from the Munich Cancer Registry. European Urology. 2014 Sep;66(3):602-3. doi: 10.1016/j.eururo.2014.04.009.
  6. Culp et al. Might men diagnosed with metastatic prostate cancer benefit from definitive treatment of the primary tumor? A SEER-based study. European Urology. 2014 Jun;65(6):1058-66. doi: 10.1016/j.eururo.2013.11.012.
  7. Fossati N. et al. Identifying optimal candidates for local treatment of the primary tumor among patients diagnosed with metastatic prostate cancer: a SEER-based study. European Urology. 2015 Jan;67(1):3-6. doi: 10.1016/j.eururo.2014.08.056. 
  8. Pompe R. et al. Prostate 2018
  9. Tilki et al. Local treatment for metastatic prostate cancer: A systematic review. International Journal of Urology. 2018 https://doi.org/10.1111/iju.13535 

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