Treatment options

Several treatment approaches are currently available for management of PC. The choice of treatment is made based on Gleason score, tumor volume, and differentiation of organ-confined disease from local or distant metastatic extension.

The National Comprehensive Cancer Network (NCCN) guidelines15 are quite useful resources for patients and health-care providers searching for optimal modalities according to PC grade and stage. NCCN data are evidence-based and descriptive of risk factors, treatment options, management strategies, tree diagrams, flow charts, and side effects, all intended for objective decision-making. 


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Conservative management. Conservative treatment of PC involves watchful waiting (WW) or hormonal therapy with luteinizing hormone-releasing hormone (LHRH) agonists. The intent is not curative but palliative.15 The WW approach is appropriate for stage T1c PC (increased PSA, normal DRE, nonpalpable tumor), especially for men with limited life expectancy (i.e., <10 years), and involves careful observation, periodic testing every three to six months for progression, and no initial treatment.15

Evidence of disease progression in the form of rising PSA, new or enlarging prostate masses on DRE, and increasing tumor volume or Gleason score of 7 to 10 on biopsy would mandate active intervention with androgen deprivation therapy, radiation therapy, and perhaps taxane chemotherapy.

In a CDC survey of 3,300 men in seven states with localized PC, regional preferences were apparent in men choosing radical prostatectomy (RP) (39.7%), radiation therapy (31.4%), WW (18.6%), and hormone therapy (10.3%).3 Men opting for WW over RP were of older age, black race, single, and had non-screening-detected PC, normal DRE, low Gleason score (<8), and PSA >20. While overall survival benefit was observed only at five years in the RP group, no reduction in PC mortality was evident.

In addition, regional differences were also correlated with overall survival. These data indicate that how, and whether, PC is treated may depend significantly on one’s state of residence as much as on clinical variables. The Prostate Cancer Intervention Versus Observation Trial (PIVOT) was the first RCT in the United States to compare RP with WW.4 Initiated in 1994, the study involved 731 men with localized PC followed for 12 years at 52 U.S. centers.

Gleason scores were <6, and median PSA was 10. The results of the trial demonstrated no benefit for RP compared with WW in all-cause mortality or in PC-specific mortality at four and 12 years follow-up. These data lend support to WW strategies for men with localized PC, especially those with low PSA and definably low-risk disease.

Surgical management. Definitive therapy consists of RP or radiation therapy.2,15 Removal of all malignant PC tissue, including pelvic nodes, is the curative intent of RP. Retropubic and perineal operative approaches and robotic assistance enhance surgical precision for nerve-sparing procedures and reduce postoperative complications of erectile dysfunction (ED) and incontinence.

The Scandinavian Prostate Cancer Group Study Number 4 demonstrated reductions in PC-related and all-cause mortality and risk of metastases in men younger than age 65 years who elected RP over WW, especially with low-risk tumors.1,16 This trial, however, also revealed adverse decrements in quality of life, particularly waning erectile function, diminished continence, and adverse psychological effects after RP.

The Veterans Administration Cooperative Urological Research Group trial involved 142 men with stage I and stage II PC treated with RP or placebo and followed the participants for 23 years. No advantage of RP over WW was demonstrated in either stage or in both stages combined.17 For men with post-prostatectomy ED or incontinence, numerous options exist.

Pharmacologic therapies for ED include such oral phosphodiesterase-5 inhibitors as sildenafil (Revatio, Viagra), vardenafil (Levitra, Staxyn), and tadalafil (Adcirca, Cialis).15 Penile implants and inflatable prostheses are effective in men with ED. Kegel exercises, anticholinergics, and urethral dilation or stenting may be beneficial for incontinence.

All of the above are intended to promote improved quality of life after RP.15 Available studies, including RCTs, do not provide consistent evidence that RP lowers overall or PC-specific mortality.12

Nor does RP improve quality of life in men with organ-confined PC. It would seem that some men who undergo surgical intervention must pay a substantial price in the short term in hope of an elusive long-term cure.

Practice implications

PC detection and treatment strategies are influenced by current scientific data, recommended therapies with narrow risk/benefit profiles, quality-of-life concerns, and personal perceptions and values prior to initiating treatment.

Patient involvement in treatment choice is especially important in early-stage, low-risk PC, where WW is a viable option, especially in older men with limited life expectancy (<10 years).3

Although evidence is conflicting, RP appears more appropriate for younger men with organ-confined malignancy and higher Gleason scores, in which case curative resection is clinically attractive for preventing disease progression, distant metastasis, and tumor recurrence in anticipation of >10 years of life expectancy.Large-scale RCTs are underway to further clarify treatment decisions for men with PC.
The Prostate, Lung, Colorectal, and Ovary study, involving 76,693 U.S. men over the span of 13 years, and the European Randomized Screening for Prostate Cancer study, involving 182,160 men in Europe over the span of nine years, are promising and intended to further define relative mortality benefits of PC screening. 
Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.
Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.18 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status. It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”19

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Criteria are being evaluated for selective identification of tumors destined to become more aggressive and metastatic, thereby warranting closer surveillance or more intensive oncologic intervention at earlier dates. New candidate biomarkers in prostate tissue may become useful in creating a genetic fingerprint of tumors likely to become aggressive and invasive.

Current genes are still research-based and include such sequenced peptides as GSTP-1, RASSFIA, AMACR, PBOV1, hepsin, DD3, and NMP48.18 Future laboratory developments may allow complementary determination of histologic features and molecular biology panels to predict transformation of PC from indolent to important clinical status.

It is worth noting that the researcher who discovered PSA, Richard Ablin, PhD, has decreed overdiagnosis of PC by PSA “a hugely expensive public health disaster.”19

Emerging data and applied technologies are being developed to predict which PCs will awaken to progression and which will remain dormant. Such techniques should allow the PSA screening debate to settle considerably. Clinical insights are emerging toward consensus for patients and providers searching for answers to the dilemma of whether to screen for PC or not.

Ms. McIver is a physician assistant at Peachtree Dunwoody Dermatology in Atlanta. Dr. Stallings and Dr. Felz are associate professors in the physician assistant department at Georgia Regents University in Augusta. y benefits of PC screening.

References

  1. Hegarty J, Beirne PV, Walsh E, et al. Radical prostatectomy versus watchful waiting for prostate cancer. Cochrane Database Syst Rev. 2010;11:CD006590.
  2. Centers for Disease Control and Prevention. Basic information about prostate cancer. Available at http://www.cdc.gov/cancer/prostate/basic_info/index.htm.
  3. Schymura MJ, Kahn AR, German RR, et al. Factors associated with initial treatment and survival for clinically localized prostate cancer: results from the CDC-NPCR Patterns of Care Study (PoC1). BMC Cancer. 2010;10:152. Available at http://www.biomedcentral.com/1471-2407/10/152.
  4. Wilt TJ, Brawer MK, Jones KM, et al. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012;367:203-213. Available at http://www.nejm.org/doi/full/10.1056/NEJMoa1113162.
  5. Surveillance, epidemiology, and end results program. SEER cancer statistics review (CSR) 1975-2010. Available at seer.cancer.gov/csr/1975_2010/.
  6. Centers for Disease Control and Prevention. Prostate cancer rates by race and ethnicity. Available at http://www.cdc.gov/cancer/prostate/statistics/race.htm.
  7. Abouassaly R, Thompson IM, Platz EA et al. Epidemiology, etiology, and prevention of prostate cancer. In: Campbell-Walsh Urology 2007; 9th edition; Wain AJ, ed. Philadelphia, Pa.: Saunders; 2854-2873.
  8. PubMed Health. Prostate cancer. Available at http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001418/.
  9. Chornokur G, Dalton K, Borysova ME, Kumar NB. Disparities at presentation, diagnosis, treatment, and survival in African American men, affected by prostate cancer. Prostate. 2011;71:985-997. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3083484/.
  10. Zeigler-Johnson C. CYP3A4: a potential prostate cancer risk factor for high-risk groups. Clin J Oncol Nurs. 2001;5:153-154.
  11. Bostwick DG, Burke HB, Djakiew D, et al. Human prostate cancer risk factors. Cancer. 2004;101:2371-2490. Available at onlinelibrary.wiley.com/doi/10.1002/cncr.20408/full.
  12. Wilt TJ, MacDonald R, Rutks I, et al. Systematic review: comparative effectiveness and harms of treatments for clinically localized prostate cancer. Ann Intern Med. 2008;148:435-448. Available at annals.org/article.aspx?articleid=740046.
  13. Moyer VA; U.S. Preventive Services Task Force. Screening for prostate cancer:  U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2012;157:120-134. Available at annals.org/article.aspx?articleid=1216568.
  14. UPMC CancerCenter. Prostate and urologic cancers. Available at http://www.upmccancercenter.com/prostateUrologicCancer/.
  15. National Comprehensive Cancer Network. NCCN Guidelines for Patients. Prostate cancer. Available at http://www.nccn.org/patients/guidelines/prostate/index.html.
  16. Bill-Axelson A, Holmberg L, Ruutu M, et al. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011;364:1708-1717.
  17. Byar DP, Corle DK. VACURG randomised trial of radical prostatectomy for stages I and II prostatic cancer. Veterans Administration Cooperative Urological Research Group. Urology. 1981;17:7-11.
  18. De Angelis G, Rittenhouse HG, Mikolajczyk SD, et al. Twenty years of PSA: From prostate antigen to tumor marker. Rev Urol. 2007;9:113-123. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2002501/.
  19. The New York Times. The great prostate mistake. Available at http://www.nytimes.com/2010/03/10/opinion/10Ablin.html.

All electronic documents accessed March 15, 2014.