Locally advanced disease

From Cancer Guidelines Wiki

Locally advanced disease

(Locally advanced/high-risk prostate cancer—de novo presentation (clinical stage T3–4, and/or early-stage disease with PSA>20)

Introduction

In these guidelines locally advanced/high risk prostate cancer is usually defined by clinical stage T3-4 and or early stage disease with PSA>20. However, to establish with certainty that it is locally advanced can be difficult and apart from clinical staging and the level of PSA, MRI scans can sometimes be of assistance as well as CT pelvis but both have low sensitivity. The presence of positive margins in the surgically resected specimen also points to the potential for locally advanced disease as does an early rise in the PSA, the rate of rise prior to localised treatment has also been suggested as a potential indicator of metastatic disease. However, in most cases it is the persistent rise in the PSA that has become a surrogate marker for advanced or metastatic disease after surgical resection of the prostate. Post radiotherapy if the PSA reaches its nadir and then starts to rise this is usually used as a surrogate marker of advanced disease. A measurable PSA after radical prostatectomy does not always indicate residual disease, as it could be due rarely to residual benign tissue. Biopsy of the prostatic bed can be performed to try to obtain tissue and /or monitoring of the rate of rise of the PSA in conjunction with knowledge of the Gleason score and presence of positive or negative margins may provide a means of determining whether the rise is due to a small remnant of benign tissue rather than metastatic disease.

Androgen Deprivation can be achieved in a number of ways. Testicular androgen production can be prevented by surgical castration, by chemical castration through the use of LHRH agonists, or by suppression of androgen production by oestrogens although because of undesirable cardiac side effects oral oestrogens are now rarely used. The other strategy is to use steroidal and non steroidal anti-androgens that compete with both testicular and andrenal androgens for the androgen receptor binding sites. These agents can be used singly and or in combination. It is important to note that there are some restrictions regarding the prescribing of these agents. LHRH agonists are available on the RPBS and anti androgens are only available on the PBS (authority) in combination with ADT. The non steroidal anti-androgens, bicalutamide and flutamide are approved only for use for stage D (metastatic) disease in combination with LHRH agonist therapy whereas the non-steroidal antiandrogen, nilutamide, is approved for use in combination with LHRH agonists or orchidectomy for the treatment of stage C (locally advanced) or D (metastatic prostate cancer). In contrast, the steroidal anti-androgen, cyproterone acetate is approved for the treatment of “advanced” prostate cancer.

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Clinical questions

Androgen deprivation therapy (ADT)

Radiotherapy

Radiotherapy and androgen deprivation therapy (ADT)

Surgery

Surgery plus androgen deprivation therapy

Chemotherapy

Bisphosphonates

  • See Bisphosphonates under castration-resistant prostate cancer for a discussion of a single trial of bisphosphonates for locally advanced disease.

Pathologic T3/T4 disease post radical surgery

Node-positive disease