First-line surgical management of high-risk, localized and locally advanced prostate cancer

For many years surgery was considered to be inappropriate for most men with locally advanced prostate cancer — most particularly those with positive lymph nodes (TxN1Mx) at the time of surgery.

Then, initially in about 1990, Horst Zinke and other surgeons at the Mayo Clinic in Rochester, MN, started to operate regularly on such patients based on the idea that surgical “debulking” of the primary tumor would lower risk for future progression. The majority of these patients would also get some form of adjuvant therapy (e.g., hormone therapy) to assist in minimizing the risk of progression. In one of a whole series of papers published over the years, they concluded that, “RP as part of a multimodal treatment strategy for patients with cT3 disease offers cancer control and survival rates approaching those achieved for cT2 disease. Pathological grade, ploidy and margin status are all significant predictors of outcome after RP. Complications and incontinence rates in patients with cT3 disease mirror those after RP for cT2 disease.”

Initially the data from the Mayo Clinic were considered to be highly controversial, but in recent years there has been a significant uptick in the belief that surgical management may be entirely appropriate for men with locally advanced prostate cancer. Two recent articles have specifically addressed this issue.

In the first of these papers, Wiegand et al. have reported on a retrospective analysis of the outcomes from primary surgical and/or hormonal treatment of 192 men with node-positive prostate cancer treated between 1982 and 2001.

These 192 patients could be categorized into three groups:

  • Group A (N = 87) received open radical retropubic prostatectomy (RRP) alone.
  • Group B (N = 74) received hormone therapy (ADT) alone.
  • Group C (N = 31) received RRP + ADT.

The basic results of treatment were as follows:

  • Local relapse occurred in 40.2 percent of patients in Group A (35/87), in 59.5 percent of patients in Group B (44/74), but only in 12.9 percent of patients in Group C (4/31).
  • Among the patients with local relapse, symptomatic local relapse occurred in 25.7 percent of patients in Group A (9/35), in 75.0 percent of patients in Group B (33/44), and in 50.0 percent of the patients in Group C (2/4).

(Local symptomatic relapse was defined as the presence of local symptoms secondary to locally recurrent prostate cancer.)

The authors conclude that radical prostatectomy — when combined  with adjuvant hormonal therapy — provides improved local control in patients with node-positive prostate cancer. They also express the belief that this endpoint should be taken into consideration when determining the optimal treatment of patients with node-positive disease.

In the second paper, Lawrentschuk et al. offer a review of the rolew of surgery in  the current treatment of patients with high-risk localized prostate cancer.

They note that historically there have been several reasons why surgery has not, historiocally, been the preferred management approach for such patients:

  • Risk of subclinical metastatic disease (“micrometastatic” disease)
  • High rates of positive surgical margins post-surgery
  • The lack of any data from randomized clinical studies
  • The risk for suboptimal cancer control

They also observe that randomized clinical trial data comparing surgery with radiation therapy in such patients are still not available at this time.

Lawrentschuk and his colleagues argue that the appropriate selection of the “best” form of management for patients with clinically localized high-risk prostate cancer needs to take account of:

  • The reasonable  life expectancy of the patient
  • The natural history of prostate cancer
  • The curability of the disease
  • The morbidity of treatment

They also point out that:

  • Management of high-grade prostate cancer with noncurative intent greatly reduces life expectancy.
  • Radical prostatectomy (RP) and radiotherapy (RT) appear to have similar effects on quality of life.
  • In this group of patients, RP necessitates an extended pelvic lymph node dissection but nerve-sparing is a therapeutic possibility.
  • Also in this group of patients, RP may offer a significant advantage over RT in terms of local control (and maybe even survival).
  • It is much easier to administer adjuvant or salvage RT after RP than it is to provide salvage RP after RT.

They conclude that, “Surgery therefore has its place, but must be considered in the context of multimodality treatment and the risk of micrometastatic disease.”

Ongoing clinical trials may help us to better understand the optimal management of patients with high-risk localized prostate cancer (including patients with node-positive disease), but it is likely that careful decision-making in ther specific interest of individual patients will still be an important factor in overall patient management.

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