Persistent, Biologically Meaningful Prostate Cancer After 1 Year of Androgen Ablation and Docetaxel Treatment

Overview

Journal J Clin Oncol

Specialty Oncology

Date 2011 May 25

PMID 21606419

Citations 33

Authors

Vassiliki Tzelepi

Eleni Efstathiou

Sijin Wen

Patricia Troncoso

Maria Karlou

Curtis A Pettaway

Louis L Pisters

Anh Hoang

Christopher J Logothetis

Lance C Pagliaro

Affiliations

Soon will be listed here.

Abstract

Purpose: Clinicians are increasingly willing to treat prostate cancer within the primary site in the presence of regional lymph node or even limited distant metastases. However, no formal study on the merits of this approach has been reported. We used a preoperative clinical discovery platform to prioritize pathways for assessment as therapeutic targets and to test the hypothesis that the primary site harbors potentially lethal tumors after aggressive treatment.

Patients And Methods: Patients with locally advanced or lymph node-metastatic prostate cancer underwent 1 year of androgen ablation and three cycles of docetaxel therapy, followed by prostatectomy. All specimens were characterized for stage by accepted criteria. Expression of select molecular markers implicated in disease progression and therapy resistance was determined immunohistochemically and compared with that in 30 archived specimens from untreated patients with high-grade prostate cancer. Marker expression was divided into three groups: intracellular signaling pathways, stromal-epithelial interaction pathways, and angiogenesis.

Results: Forty patients were enrolled, 30 (75%) of whom underwent prostatectomy and two (5%) who underwent cystoprostatectomy. Twenty-nine specimens contained sufficient residual tumor for inclusion in a tissue microarray. Immunohistochemical analysis showed increased epithelial and stromal expression of CYP17, SRD5A1, and Hedgehog pathway components, and modulations of the insulin-like growth factor I pathway.

Conclusion: A network of molecular pathways reportedly linked to prostate cancer progression is activated after 1 year of therapy; biomarker expression suggests that potentially lethal cancers persist in the primary tumor and may contribute to progression.

Citing Articles

Comparison of Complications and Mid-term Results for Patients who Underwent Open Radical Prostatectomy for High-Risk and Oligometastatic Prostate Cancer: A Cross-Sectional Study from a Tertiary Reference Center.

Beyatli M, Duvarci M, Uzel T, Aybal H, Hamidi N, Ceylan O Ann Surg Oncol. 2024; 31(12):8438-8443.

PMID: 39196474 DOI: 10.1245/s10434-024-16104-z.

A phase I study of docetaxel plus synthetic lycopene in metastatic prostate cancer patients.

Lilly M, Wu C, Ke Y, Chen W, Soloff A, Armeson K Clin Transl Med. 2024; 14(3):e1627.

PMID: 38515274 PMC: 10958125. DOI: 10.1002/ctm2.1627.

[Local therapies for oligometastatic hormone-sensitive prostate cancer].

Falkenbach F, Steuber T, Graefen M Urologie. 2024; 63(3):215-224.

PMID: 38329485 DOI: 10.1007/s00120-024-02280-z.

Is there a role for radical prostatectomy in the management of oligometastatic prostate cancer? A systematic review.

Saouli A, Touzani A, Martini A, Beauval J, Dergamoun H, Ziouziou I Prostate Cancer Prostatic Dis. 2023; 27(4):645-653.

PMID: 37985863 DOI: 10.1038/s41391-023-00752-5.

Oligometastatic carcinoma prostate - An overview of the last decade.

Shah M, Sharma A, Hameed B, Jain R, Patil A, Karthickeyan N Indian J Urol. 2023; 39(3):195-201.

PMID: 37575157 PMC: 10419768. DOI: 10.4103/iju.iju_60_23.

References

Pandini G, Mineo R, Frasca F, Roberts Jr C, Marcelli M, Vigneri R . Androgens up-regulate the insulin-like growth factor-I receptor in prostate cancer cells. Cancer Res. 2005; 65(5):1849-57. DOI: 10.1158/0008-5472.CAN-04-1837. View

Shi Y, Chatterjee S, Brands F, Shi S, Pootrakul L, Taylor C . Role of coordinated molecular alterations in the development of androgen-independent prostate cancer: an in vitro model that corroborates clinical observations. BJU Int. 2005; 97(1):170-8. DOI: 10.1111/j.1464-410X.2006.05857.x. View

Crook J, Malone S, Perry G, Eapen L, Owen J, Robertson S . Twenty-four-month postradiation prostate biopsies are strongly predictive of 7-year disease-free survival: results from a Canadian randomized trial. Cancer. 2009; 115(3):673-9. DOI: 10.1002/cncr.24020. View

Beer T, El-Geneidi M, Eilers K . Docetaxel (taxotere) in the treatment of prostate cancer. Expert Rev Anticancer Ther. 2003; 3(3):261-8. DOI: 10.1586/14737140.3.3.261. View

Scattoni V, Montironi R, Mazzucchelli R, Freschi M, Nava L, Losa A . Pathological changes of high-grade prostatic intraepithelial neoplasia and prostate cancer after monotherapy with bicalutamide 150 mg. BJU Int. 2006; 98(1):54-8. DOI: 10.1111/j.1464-410X.2006.06204.x. View

Chen M, Johnston D, Reyes A, Soto C, Babaian R, Troncoso P . A streamlined three-dimensional volume estimation method accurately classifies prostate tumors by volume. Am J Surg Pathol. 2003; 27(10):1291-301. DOI: 10.1097/00000478-200310000-00001. View

Petrylak D, Tangen C, Hussain M, Lara Jr P, Jones J, Taplin M . Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004; 351(15):1513-20. DOI: 10.1056/NEJMoa041318. View

Chi K, Chin J, Winquist E, Klotz L, Saad F, Gleave M . Multicenter phase II study of combined neoadjuvant docetaxel and hormone therapy before radical prostatectomy for patients with high risk localized prostate cancer. J Urol. 2008; 180(2):565-70. DOI: 10.1016/j.juro.2008.04.012. View

Levine A, Liu X, Greenberg P, Eliashvili M, Schiff J, Aaronson S . Androgens induce the expression of vascular endothelial growth factor in human fetal prostatic fibroblasts. Endocrinology. 1998; 139(11):4672-8. DOI: 10.1210/endo.139.11.6303. View

10.

Baretton G, Klenk U, Diebold J, Schmeller N, Lohrs U . Proliferation- and apoptosis-associated factors in advanced prostatic carcinomas before and after androgen deprivation therapy: prognostic significance of p21/WAF1/CIP1 expression. Br J Cancer. 1999; 80(3-4):546-55. PMC: 2362324. DOI: 10.1038/sj.bjc.6690390. View

11.

Kaplan P, Mohan S, Cohen P, Foster B, Greenberg N . The insulin-like growth factor axis and prostate cancer: lessons from the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Cancer Res. 1999; 59(9):2203-9. View

12.

Mazzucchelli R, Montironi R, Santinelli A, Lucarini G, Pugnaloni A, Biagini G . Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients. Prostate. 2000; 45(1):72-9. DOI: 10.1002/1097-0045(20000915)45:1<72::aid-pros9>3.0.co;2-u. View

13.

Verhagen P, Schroder F, Collette L, Bangma C . Does local treatment of the prostate in advanced and/or lymph node metastatic disease improve efficacy of androgen-deprivation therapy? A systematic review. Eur Urol. 2010; 58(2):261-9. DOI: 10.1016/j.eururo.2010.05.027. View

14.

Stewart R, Panigrahy D, Flynn E, Folkman J . Vascular endothelial growth factor expression and tumor angiogenesis are regulated by androgens in hormone responsive human prostate carcinoma: evidence for androgen dependent destabilization of vascular endothelial growth factor transcripts. J Urol. 2001; 165(2):688-93. DOI: 10.1097/00005392-200102000-00095. View

15.

Sanchez-Ortiz R, Troncoso P, Babaian R, Lloreta J, Johnston D, Pettaway C . African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men. Cancer. 2006; 107(1):75-82. DOI: 10.1002/cncr.21954. View

16.

Mathew P, DiPaola R . Taxane refractory prostate cancer. J Urol. 2007; 178(3 Pt 2):S36-41. DOI: 10.1016/j.juro.2007.04.032. View

17.

Nakano K, Fukabori Y, Itoh N, Lu W, Kan M, McKeehan W . Androgen-stimulated human prostate epithelial growth mediated by stromal-derived fibroblast growth factor-10. Endocr J. 1999; 46(3):405-13. DOI: 10.1507/endocrj.46.405. View

18.

Stanbrough M, Bubley G, Ross K, Golub T, Rubin M, Penning T . Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006; 66(5):2815-25. DOI: 10.1158/0008-5472.CAN-05-4000. View

19.

Planz B, Wang Q, Kirley S, Lin C, McDougal W . Androgen responsiveness of stromal cells of the human prostate: regulation of cell proliferation and keratinocyte growth factor by androgen. J Urol. 1998; 160(5):1850-5. DOI: 10.1016/s0022-5347(01)62431-5. View

20.

Karhadkar S, Bova G, Abdallah N, Dhara S, Gardner D, Maitra A . Hedgehog signalling in prostate regeneration, neoplasia and metastasis. Nature. 2004; 431(7009):707-12. DOI: 10.1038/nature02962. View