Devita, Hellman, and Rosenberg's Cancer

LWBK1006-21 LWW-Govindan-Review December 12, 2011 19:6

294 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

Answer 21.27. The answer is B.

Patients with a slowly increasing PSA after definitive local therapy may

have a very long natural history, with only a minority of patients having

cancer-related mortality within 10 years. Androgen ablation, especially in

elderly patients, is associated with osteoporosis, muscle loss, and changes

in lipid metabolism that may have significant impact on cardiovascular

comorbidities. High-intensity focused ultrasound for treatment of possi-

ble localized recurrence is still investigational. Single-agent antiandrogen

therapy is not approved and may lead to higher mortality in patients such

as this.

Answer 21.28. The answer is C.

This patient meets all the criteria for castrate-resistant prostate cancer,

and the only therapy demonstrated to improve survival is docetaxel-based

chemotherapy. Nevertheless, there remains controversy regarding the tim-

ing of such therapy in otherwise asymptomatic men. Active surveillance is

thus reasonable. High-dose ketoconazole has been demonstrated to lead

to PSA decreases in up to 30% of men in this situation in several studies.

Although thalidomide has been investigated, it has minimal activity as a

single agent and is not indicated.

Answer 21.29. The answer is B.

Multiple studies confirm marked differences in prostate cancer incidence

and mortality between various countries that are not explainable by any

kind of ascertainment bias. Changes in incidence and mortality in pop-

ulations migrating from a country with a low incidence to a country

with a high incidence strongly suggest that there are significant dietary

or lifestyle contributors to prostate cancer development. There is now

also confirmation of a genetic risk component because genetic polymor-

phisms, including several on 8q24, have been found to be closely associ-

ated with prostate cancer. In fact, the large difference in prostate cancer

mortality between African Americans and Caucasian Americans cannot

be explained by socioeconomic factors alone.

Answer 21.30. The answer is C.

NKX3.1 transcription factor inactivation can be detected in the earli-

est identifiable PIN lesions. In contrast, PTEN loss is far more common

in advanced disease. GSTis also commonly seen at all disease stages,

including PIN. Translocation of the androgen-responsive gene promoter

from TMPRSS2 to ETS family transcription factors is common in early

tumors, but not in PIN.

Answer 21.31. The answer is D.

Although the androgen receptor does have cytoplasmic effects, some

of which may be important to prostate cancer oncogenesis, the major-

ity of its effects occur in the nucleus where it modifies expression of

genes with an androgen-responsive promoter. Upregulation of androgen