Therapy-associated effects in the prostate gland
John R Srigley
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Search for more papers by this authorBrett Delahunt
Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
Search for more papers by this authorAndrew J Evans
Laboratory Medicine Program, Department of Pathology, University Health Network, Toronto General Hospital, Toronto, ON, Canada
Search for more papers by this authorJohn R Srigley
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada
Search for more papers by this authorBrett Delahunt
Department of Pathology and Molecular Medicine, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand
Search for more papers by this authorAndrew J Evans
Laboratory Medicine Program, Department of Pathology, University Health Network, Toronto General Hospital, Toronto, ON, Canada
Search for more papers by this authorAbstract
Srigley J R, Delahunt B & Evans A J (2012) Histopathology 60, 153–165
Therapy-associated effects in the prostate gland
Diverse therapies are used to treat both benign prostatic hyperplasia and adenocarcinoma. Transurethral resection, a common surgical procedure, may give rise to characteristic necrobiotic granulomas that manifest in subsequent pathology samples. Radiation and hormone therapy have traditionally been used in prostatic adenocarcinoma. Morphological effects are often identified in needle biopsy specimens, transurethral resectates, and radical prostatectomy specimens. A range of histological changes are noted in the non-neoplastic prostate tissue, as well as in the pre-neoplastic and carcinomatous areas. Other ablative therapies, such as cryotherapy, and emerging focal therapies, including high-intensity focused ultrasound, photodynamic therapy, and interstitial laser thermotherapy, may have morphological effects on prostate tissue. It is important for the pathologist to be aware of the spectrum of histological changes affecting the prostate gland post-therapy. The treatment effects may obscure residual carcinoma, and make measurements of tumour extent and stage difficult. Furthermore, some therapies can profoundly alter the neoplastic glands to such an extent that Gleason scoring is no longer valid. As new therapies are developed for prostate cancer, it is important to document their effects on benign and malignant prostate tissue and to understand possible implications for traditional prognostic factors, especially Gleason grade.
References
- 1 Humphrey PA . Prostate pathology . Chicago, IL : American Society for Clinical Pathology , 2003 ; 456 – 476 .
- 2 Petraki CD , Sfikas CP . Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma . Histol. Histopathol. 2007 ; 1 ; 107 – 118 .
- 3 Mies C , Balogh K , Stadecker M . Palisading prostate granulomas following surgery . Am. J. Surg. 1984 ; 8 ; 217 – 221 .
- 4 Henry L , Wagner B , Faulkner MK et al. Metal deposition in post-surgical granulomas of the urinary tract . Histopathology 1993 ; 22 ; 457 – 465 .
- 5 Epstein JI , Hutchins GM . Granulomatous prostatitis: distinction among allergic, nonspecific, and post-transurethral resection lesions . Hum. Pathol. 1984 ; 15 ; 818 – 825 .
- 6 Sandler HM , Liu P , Dunn RL . Reduction in patient-reported acute morbidity in prostate cancer patients treated with 81-Gy intensity-modulated radiotherapy using reduced planning target volume margins and electromagnetic tracking: assessing the impact of margin reduction study . Urology 2010 ; 75 ; 1004 – 1008 .
- 7 Rosenthal SA , Sandler HM . Treatment strategies for high-risk locally advanced prostate cancer . Nat. Rev. Urol. 2010 ; 7 ; 31 – 38 .
- 8 Gomez-Iturriaga PA , Crook J , Borg J et al. Biochemical disease-free rate and toxicity for men treated with iodine-125 prostate brachytherapy with d(90) >=180 Gy . Int. J. Radiat. Oncol. Biol. Phys. 2010 ; 78 ; 422 – 427 .
- 9 Souhami LB , Bae K , Pilepich M et al. Impact of the duration of adjuvant hormonal therapy in patients with locally advanced prostate cancer treated with radiotherapy: a secondary analysis of RTOG 85-31 . J. Clin. Oncol. 2009 ; 27 ; 2137 – 2143 .
- 10 Katz AJ . CyberKnife radiosurgery for prostate cancer . Technol. Cancer Res. Treat. 2010 ; 9 ; 463 – 472 .
- 11 Heidenreich A , Richter S , Thuer D . Prognostic parameters, complications, and oncologic and functional outcome of salvage radical prostatectomy for locally recurrent prostate cancer after 21st-century radiotherapy . Eur. Urol. 2010 ; 57 ; 437 – 443 .
- 12 Têtu B . Morphological changes induced by androgen blockade in normal prostate and prostatic carcinoma . Best Pract. Res. Clin. Endocrinol. Metab. 2008 ; 22 ; 271 – 283 .
- 13 Evans AJ , Ryan P , van der Kwast T . Treatment effects in the prostate including those associated with traditional and emerging therapies . Adv. Anat. Pathol. 2011 ; 18 ; 281 – 293 .
- 14
Crook JM
,
Bahadur YA
,
Robertson SJ
et al.
Evaluation of radiation effect, tumor differentiation and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma
.
Cancer
1997
;
79
;
81
–
89
.
10.1002/(SICI)1097-0142(19970101)79:1<81::AID-CNCR12>3.0.CO;2-2 CAS PubMed Web of Science® Google Scholar
- 15 Crook JM , Malone S , Perry G et al. Twenty-four month postradiation prostate biopsies are strongly predictive of 7-year disease free survival: results from a Canadian randomized trial . Cancer 2009 ; 115 ; 673 – 679 .
- 16 Gaudin PB , Zelefsky MJ , Leibel SA . Histopathological effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues . Am. J. Surg. Pathol. 1999 ; 23 ; 1021 – 1031 .
- 17 Bocking A , Aufferman W . Cytologic grading of therapy-induced tumor regression in prostatic carcinoma: proposal of a new system . Diagn. Cytopathol. 1987 ; 3 ; 108 – 111 .
- 18 Crawford ED . Hormonal therapy in prostate cancer: historical approaches . Rev. Urol. 2006 ; 6 ( Suppl. 7 ); S3 – S11 .
- 19 Huggins C , Hodges CV . Studies on prostatic cancer: (1) The effect of estrogen and of androgen injection on serum phosphates in metastatic carcinoma of the prostate . Cancer Res. 1941 ; 1 ; 293 – 297 .
- 20 Huggins C , Stevens RE , Hodges CV . Studies on prostatic cancer: (II) The effects of castration on advanced carcinoma of the prostate gland . Arch. Surg. 1941 ; 43 ; 209 – 223 .
- 21
Franks LM
.
Estrogen-treated prostatic cancer. The variation in responsiveness of tumor cells
.
Cancer
1960
;
13
;
490
–
501
.
10.1002/1097-0142(196005/06)13:3<490::AID-CNCR2820130311>3.0.CO;2-U CAS PubMed Web of Science® Google Scholar
- 22 Grignon D , Troster M . Changes in immunohistochemical staining in prostatic adenocarcinoma following diethylstilbestrol therapy . Prostate 1985 ; 7 ; 195 – 202 .
- 23 Brawer MK . Hormonal therapy for prostate cancer . Rev. Urol. 2006 ; 8 ( Suppl. 2 ); S35 – S47 .
- 24 Klotz LH , Goldenberg SL , Jewett M et al. CUOG randomized trial of neoadjuvant androgen ablation before radical prostatectomy: 36-month post-treatment PSA results . Urology 1999 ; 53 ; 757 – 763 .
- 25 Heymann JJ , Benson MC , O’Toole KM et al. Phase II study of neoadjuvant androgen deprivation followed by external beam radiotherapy with 9 months of androgen deprivation for intermediate- to high-risk localized prostate cancer . J. Clin. Oncol. 2007 ; 25 ; 8 – 9 .
- 26 Pettaway CA , Pisters LL , Troncoso P et al. Neoadjuvant chemotherapy and hormonal therapy followed by radical prostatectomy: feasibility and preliminary results . J. Clin. Oncol. 2000 ; 18 ; 1050 – 1057 .
- 27 Thompson IM , Goodman PJ , Tangen CM et al. The influence of finasteride on the development of prostate cancer . N. Engl. J. Med. 2003 ; 349 ; 215 – 224 .
- 28 Andriole G , Bostwick D , Civantos F et al. The effects of 5α-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge . J. Urol. 2005 ; 174 ; 2098 – 2104 .
- 29 Wilt TJ , Macdonald R , Haggarty K et al. 5α-Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review . BJU Int. 2010 ; 106 ; 1444 – 1451 .
- 30 Têtu B , Srigley JR , Boivin JC et al. Effect of combination endocrine therapy (LHRH agonist and flutamide) on normal prostate and prostatic adenocarcinoma. A histopathologic and immunohistochemical study . Am. J. Surg. Pathol. 1991 ; 15 ; 111 – 120 .
- 31 Bullock MJ , Srigley JR , Klotz LH et al. Pathologic effects of neoadjuvant cyproterone acetate on nonneoplastic prostate, prostatic intraepithelial neoplasia, and adenocarcinoma. A detailed analysis of radical prostatectomy specimens from a randomized trial . Am. J. Surg. Pathol. 2002 ; 26 ; 1400 – 1413 .
- 32 Vallancourt L , Têtu B , Fradet Y et al. Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma: a randomized study . Am. J. Surg. Pathol. 1996 ; 20 ; 86 – 93 .
- 33
Civantos F
,
Marcial MA
,
Banks ER
et al.
Pathology of androgen deprivation therapy in prostate carcinoma: a comparative study of 173 patients
.
Cancer
1995
;
75
;
1634
–
1641
.
10.1002/1097-0142(19950401)75:7<1634::AID-CNCR2820750713>3.0.CO;2-# CAS PubMed Web of Science® Google Scholar
- 34 Armas OA , Aprikian AG , Melamed J et al. Clinical and pathological effects of neoadjuvant total androgen ablation therapy on clinically localized prostatic adenocarcinoma . Am. J. Surg. Pathol. 1994 ; 18 ; 979 – 991 .
- 35 Bostwick DG , Qian J . Effect of androgen deprivation therapy on prostatic intraepithelial neoplasia . Urology 2001 ; 2 ( Suppl. 1 ); 91 – 93 .
- 36 Kang TY , Nichols P , Skinner E . Functional heterogeneity of prostatic intraepithelial neoplasia: the duration of hormonal therapy influences the response . BJU Int. 2007 ; 99 ; 1024 – 1027 .
- 37 van der Kwast TH , Labrie F , Têtu B . Persistence of high-grade prostatic intra-epithelial neoplasia under combined androgen blockade therapy . Hum. Pathol. 1999 ; 30 ; 1503 – 1507 .
- 38 van der Kwast TH , Têtu B , Candas B et al. Prolonged neoadjuvant combined androgen blockade leads to a further reduction of prostatic tumor volume: three versus 6 months of endocrine therapy . Urology 1999 ; 53 ; 523 – 529 .
- 39 Montironi R , Magi-Galluzzi C , Muzzonigro G et al. Effects of combination endocrine treatment on normal prostate, prostatic intraepithelial neoplasia and prostatic adenocarcinoma . J. Clin. Pathol. 1994 ; 47 ; 906 – 913 .
- 40 Efstathiou E , Abrahams NA , Tibbs RF et al. Morphologic characterization of preoperatively treated prostate cancer: toward a post-therapy histologic classification . Eur. Urol. 2010 ; 57 ; 1030 – 1038 .
- 41 Labrie F , Cusan L , Gomez J et al. Neoadjuvant hormonal therapy: the Canadian experience . Urology 1997 ; 49 ; 56 – 64 .
- 42 Witjes WPJ , Schulman CC , Debruyne FMJ . Preliminary results of a prospective randomized study comparing radical prostatectomy versus radical prostatectomy associated with neoadjuvant hormonal combination therapy in T2-3N0M0 prostatic carcinoma . Urology 1997 ; 49 ; 65 – 69 .
- 43 Bono AV , Pagano F , Montironi R et al. Effect of complete androgen blockade on pathologic stage and resection margin status of prostate cancer: progress pathology report of the Italian PROSIT study . Urology 2001 ; 57 ; 117 – 121 .
- 44 Gleave ME , Goldenberg SL , Jones EC et al. Biochemical and pathological effects of 8 months of neoadjuvant androgen withdrawal therapy before radical prostatectomy in patients with clinically confined prostate cancer . J. Urol. 1996 ; 155 ; 213 – 219 .
- 45 Gleave ME , Goldenberg SL , Chin JL et al. Randomized comparative study of 3 versus 8-month neoadjuvant hormonal therapy before radical prostatectomy: biochemical and pathological effects . J. Urol. 2001 ; 166 ; 500 – 506 .
- 46 Schulman CC , Debruyne FM , Forster G et al. 4-year follow-up results of a European prospective randomized study on neoadjuvant hormonal therapy prior to radical prostatectomy in T2-3N0M0 prostate cancer. European Study Group on Neoadjuvant Treatment of Prostate Cancer . Eur. Urol. 2000 ; 38 ; 706 – 718 .
- 47 Yee DS , Lowrance WT , Eastham JA et al. Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial . BJU Int. 2010 ; 105 ; 185 – 190 .
- 48 Lieberman R . Chemoprevention of prostate cancer: current status and future directions . Cancer Metastasis Rev. 2002 ; 21 ; 297 – 301 .
- 49 Earnshaw SR , McDade CL , Black LK et al. Cost effectiveness of 5-alpha reductase inhibitors for the prevention of prostate cancer in multiple patient populations . Pharmacoeconomics 2010 ; 28 ; 489 – 505 .
- 50 Rubin MA , Allory Y, Molinié V et al. Effects of long-term finasteride treatment on prostate cancer morphology and clinical outcome . Urology 2005 ; 66 ; 930 – 934 .
- 51 Lucia MS , Epstein JI , Goodman PJ et al. Finasteride and high-grade prostate cancer in the prostate cancer prevention trial . J. Natl Cancer Inst. 2007 ; 99 ; 1375 – 1383 .
- 52 Cohen YC , Liu KS , Heyden NL et al. Detection bias due to the effect of finasteride on prostate volume: a modeling approach for analysis of the Prostate Cancer Prevention Trial . J. Natl. Cancer Inst. 2007 ; 99 ; 1366 – 1374 .
- 53 Klotz L , Drachenberg D , Fradet Y et al. Gleason grading controversies: what the chemoprevention trials have taught us . Can. J. Urol. 2009 ; 3 ( Suppl. 2 ); S115 – S120 .
- 54 Lebdai S , Bigot P , Azzouzi AR . High-grade prostate cancer and finasteride . BJU Int. 2010 ; 105 ; 456 – 459 .
- 55
Têtu B
,
Ro JY
,
Ayala AG
et al.
Small cell carcinoma of the prostate. Part I. A clinicopathologic study of 20 cases
.
Cancer
1987
;
59
;
1803
–
1809
.
10.1002/1097-0142(19870515)59:10<1803::AID-CNCR2820591019>3.0.CO;2-X CAS PubMed Web of Science® Google Scholar
- 56 Evans A , Humphrey PA , Belani J et al. Large cell neuroendocrine carcinoma of prostate: a clinicopathologic summary of 7 cases of a rare manifestation of advanced prostate cancer . Am. J. Surg. Pathol. 2006 ; 30 ; 684 – 693 .
- 57 Abrahamsson PA , Falkmer S , Fält K et al. The course of neuroendocrine differentiation in prostatic carcinomas: an immunohistochemical study testing chromogranin A as an ‘endocrine marker’ . Pathol. Res. Pract. 1989 ; 185 ; 373 – 380 .
- 58 Wang W , Epstein JI . Small cell carcinoma of the prostate. A morphologic and immunohistochemical study of 95 cases . Am. J. Surg. Pathol. 2008 ; 32 ; 65 – 71 .
- 59 Epstein JI , Allsbrook WC , Amin MB et al. The 2005 International Society of Urological Pathology (ISUP) consensus conference on Gleason grading of prostatic carcinoma . Am. J. Surg. Pathol. 2005 ; 29 ; 1228 – 1242 .
- 60 Stein ME , Bernstein Z , Abacioglu U et al. Small cell (neuroendocrine) carcinoma of the prostate: etiology, diagnosis, prognosis, and therapeutic implications – a retrospective study of 30 patients from the rare cancer network . Am. J. Med. Sci. 2008 ; 336 ; 478 – 488 .
- 61 Armstrong AJ , George DJ . New drug development in metastatic prostate cancer . Urol. Oncol. 2008 ; 26 ; 430 – 437 .
- 62 Schrijvers D , Van Erps P , Cortvriend J . Castration-refractory prostate cancer: new drugs in the pipeline . Adv. Ther. 2010 ; 27 ; 285 – 296 .
- 63 Clark PE , Peereboom DM , Drejcer D et al. Phase II trial of neoadjuvant estramustine and etoposide plus radical prostatectomy for locally advanced prostate cancer . Urology 2001 ; 57 ; 281 – 285 .
- 64 Magi-Galluzzi C , Zhou M , Reuther AN et al. Neoadjuvant docetaxel treatment for locally advanced prostate cancer: a clinicopathologic study . Cancer 2007 ; 110 ; 1248 – 1254 .
- 65 O’Brien C , Lawrence TD , Higano CS et al. Histologic changes associated with neoadjuvant chemotherapy are predictive of nodal metastases in patients with high-risk prostate cancer . Anat. Pathol. 2010 ; 133 ; 654 – 661 .
- 66 Rubin MA . Targeted therapy of prostate cancer: new roles for pathologists – prostate cancer . Mod. Pathol. 2008 ; 21 ; S44 – S55 .
- 67 Fitzpatrick JM , Mebust WK . Minimally invasive and endoscopic management of benign prostatic hyperplasia . In PC Walsh , AB Retik , ED Vaughn et al. eds . Campbells urology , 8th edn . Philadephia, PA : Saunders , 2002 ; 1379 – 1422 .
- 68 Lindner U , Trachtenberg J , Lawrentschuk N . Focal therapy in prostate cancer: modalities, findings and future considerations . Nat. Rev. Urol. 2010 ; 7 ; 562 – 571 .
- 69 Pisters LL . Cryotherapy for prostate cancer: ready for primary time? Curr. Opin. Urol. 2010 ; 20 ; 218 – 222 .
- 70 Shabaik A , Wilson S , Bidair M et al. Pathologic changes in prostate biopsies following cryoablation therapy of prostate carcinoma . J. Urol. Pathol. 1995 ; 3 ; 183 – 193 .
- 71 Borkowski O , Robinson MJ , Poppiti RJ Jr et al. Histologic findings in postcryosurgical prostatic biopsies . Mod. Pathol. 1996 ; 9 ; 807 – 811 .
- 72 Ellis DS , Manny TB , Newcastle JC . Focal cryosurgery followed by penile rehabilitation as primary treatment for localized prostate cancer: initial results . Urology 2007 ; 70 ; 9 – 15 .
- 73 Donnelly BJ , Saliken JC , Ali-Ridha N et al. Histologic findings in the prostate two years following cryosurgical ablation . Can. J. Urol. 2001 ; 8 ; 1237 – 1239 .
- 74 Huidobro C , Bolmsjo M , Larsen T et al. Evaluation of microwave thermal therapy with histopathology, magnetic resonance imaging and temperature mapping . J. Urol. 2004 ; 171 ; 672 – 678 .
- 75 Polascik TJ , Mouraviev V . Focal therapy for prostate cancer . Curr. Opin. Urol. 2008 ; 18 ; 269 – 274 .
- 76 Zacharakis E , Ahmed HU , Ishaq A et al. The feasibility and safety of high-intensity focused ultrasound as salvage therapy for recurrent prostate cancer following external beam radiotherapy . BJU Int. 2008 ; 102 ; 786 – 792 .
- 77 Blana A , Rogenhofer S , Ganzer R et al. Eight years’ experience with high-intensity focused ultrasonography for treatment of localized prostate cancer . Urology 2008 ; 72 ; 1329 – 1333 .
- 78 Blana A , Murat FJ , Walter B et al. First analysis of the long-term results with transrectal HIFU in patients with localised prostate cancer . Eur. Urol. 2008 ; 53 ; 1194 – 1201 .
- 79 Ahmed HU , Zacharakis E , Dudderidge T et al. High-intensity-focused ultrasound in the treatment of primary prostate cancer: the first UK series . Br. J. Cancer 2009 ; 101 ; 19 – 26 .
- 80 ter Haar GR . High intensity focused ultrasound for the treatment of tumors . Echocardiography 2001 ; 18 ; 317 – 322 .
- 81 Kincaide LF , Sanghvi NT , Cummings O et al. Noninvasive ultrasonic subtotal ablation of the prostate in dogs . Am. J. Vet. Res. 1996 ; 57 ; 1225 – 1227 .
- 82 Van Leenders GJ , Beerlage HP , Ruijter ET et al. Histopathological changes associated with high-intensity focused ultrasound (HIFU) treatment for localized adenocarcinoma of the prostate . J. Clin. Pathol. 2000 ; 53 ; 391 – 394 .
- 83 Biermann K , Montironi R , Lopez-Beltran A et al. Histopathological findings after treatment of prostate cancer using high-intensity focused ultrasound (HIFU) . Prostate 2010 ; 70 ; 1196 – 1200 .
- 84 Trachtenberg J , Bogaards A , Weersink RA et al. Vascular targeted photodynamic therapy with palladium-bacteriopheophorbide photosensitizer for recurrent prostate cancer following definitive radiation therapy: assessment of safety and treatment response . J. Urol. 2007 ; 178 ; 1974 – 1979 .
- 85 Trachtenberg J , Weersink RA , Davidson SRH et al. Vascular-targeted photodynamic therapy (padoporfin, WST09) for recurrent prostate cancer after failure of external beam radiotherapy: a study of escalating light doses . BJU Int. 2008 ; 102 ; 556 – 562 .
- 86 Raz O , Haider MA , Davidson SRH et al. Real-time magnetic resonance imaging-guided focal laser therapy in patients with low-risk prostate cancer . Eur. Urol. 2010 ; 58 ; 173 – 177 .
- 87 Lindner U , Lawrentschuk N , Weersink RA et al. Focal laser ablation for prostate cancer followed by radical prostatectomy: validation of focal therapy and imaging accuracy . Eur. Urol. 2010 ; 57 ; 1111 – 1114 .
- 88 Helpap B , Oehler U , Weisser H et al. Morphology of benign prostatic hyperplasia after treatment with Sabal Extract IDS 89 or placebo . J. Urol. Pathol. 1995 ; 3 ; 175 – 182 .
- 89 Marks LS , Partin AW , Epstein JI et al. Effects of saw palmetto herbal blend in men with symptomatic benign prostatic hyperplasia . J. Urol. 2000 ; 163 ; 1451 – 1456 .