Modifications histologiques induites par les traitements conservateurs du cancer de la prostate et leurs conséquences sur l’interprétation du score de Gleason

doi:10.1016/j.annpat.2008.07.008

Annales de Pathologie

Volume 28, Issue 5, October 2008, Pages 363-373

https://doi.org/10.1016/j.annpat.2008.07.008 Get rights and content

Résumé

Si la prostatectomie totale reste le traitement de référence pour les patients ayant un cancer de prostate à risque intermédiaire ayant une espérance de vie supérieure à dix ans, dans un certain nombre de cas, des traitements non chirurgicaux peuvent être proposés : radiothérapie externe (exclusive avec ou sans escalade de dose ou combinée à une hormonothérapie), curiethérapie par implants permanents, ultrasons de haute fréquence (HIFU, Ablatherm^©), cryothérapie ou traitement hormonal exclusif. Chez les patients pour lesquels l’option thérapeutique n’a pas été la chirurgie, en cas de récidive biologique, de nouvelles biopsies peuvent être proposées afin d’affirmer la récidive locale. La confirmation de la persistance d’une infiltration tumorale est habituellement exigée avant tout traitement : chirurgie de rattrapage, cryothérapie, curiethérapie ou ultrasons focalisés de haute intensité (HIFU). Les modifications histologiques induites par ces différents traitement doivent être connues des pathologistes afin d’assurer une interprétation optimale des biopsies. Dans cette revue, nous décrirons les modifications observées au niveau de la prostate normale et celles observées dans les cancers après ces différentes modalités thérapeutiques. Nous aborderons également les modifications induites par les inhibiteurs de la 5 alpha réductase proposés comme traitement de l’hypertrophie bénigne de la prostate mais également comme facteurs de chimioprévention du cancer de prostate.

Summary

Total prostatectomy remains the main treatment for intermediate risk prostate cancer with a life expectancy greater than 10 years. In other cases non-surgical treatments can be proposed: external radiotherapy (exclusive or combined anti-androgen therapy), brachytherapy with permanent implants, high frequency ultrasounds (HIFU, Ablatherm), cryotherapy or exclusive hormonal treatment. For such patients in case of biological recurrence, prostate biopsies are usually performed in order to affirm the local recurrence. The histological confirmation of persistent tumor is usually required before any treatment: salvage surgery, cryotherapy, and brachytherapy or high intensity focused ultrasound (HIFU). Pathologists must be aware of the histological modifications induced by these different treatments in order to ensure an optimal interpretation of the biopsies. In this review, we describe the modifications observed in the normal prostate and in cancers after these various therapeutic methods, and also after alpha reductase inhibitors proposed as treatment of benign prostate hypertrophy and prostate cancer chemoprevention.

Section snippets

Traitements conservateurs du cancer de prostate

En France, comme dans la plupart des pays développés, le cancer de prostate est le premier cancer chez l’homme de plus de 50 ans [1], [2]. Le nombre de nouveaux cancers diagnostiqués en France est estimé en 2008 à 60 000 nouveaux cas par an [3]. Si la prostatectomie totale reste le traitement de référence pour les patients ayant un cancer de prostate à risque intermédiaire ayant une espérance de vie supérieure à dix ans, dans un certain nombre de cas des traitements non chirurgicaux peuvent être

Traitement hormonal et prostate

Les traitements anti-androgéniques font appel à plusieurs modalités thérapeutiques : pulpectomie, estrogénothérapie, administration d’analogue de la LH-RH, prise de médicaments bloquant la conversion de la testostérone dans sa forme active di-hydro-testostérone (DHT) : inhibiteurs de la 5 alpha reductase, ou bloquant le récepteur aux androgènes (Flutamide), blocage androgénique complet par rajout d’un anti-androgène à l’analogue de la LH-RH ou après pulpectomie [1] (Tableau 1). Les

Modifications post-radiques

Bien qu’il soit rare de recevoir une pièce de prostatectomie totale après irradiation, les modifications induites par la radiothérapie ou la curiethérapie mérite d’être connue des pathologistes (Tableau 3).

Chimiothérapie

Actuellement, quelques patients bénéficient d’un protocole thérapeutique associant une hormonothérapie néo-adjuvante à une chimiothérapie pré-opératoire (Taxotère^®), afin d’obtenir une fonte tumorale [43], [44]. Lorsque ces patients sont opérés, les pièces de prostatectomie radicale présentent des modifications histologiques identiques à celles observées en cas de blocage anti-androgénique complet, associé à d’importants phénomènes inflammatoires [45], pouvant réaliser des aspect de « vanishing

Autres traitements

Ces dernières années, de nouvelles modalités thérapeutiques ont vu le jour : ultrasons focalisés de haute intensité (HIFU, ablatherm ^©), cryothérapie, résection par laser (Tableau 4). Ces traitements sont utilisés comme traitement initial chez les sujets ayant un cancer localisé de haut risque et une espérance de vie inférieure à sept ans, ou en seconde intention, en cas de récidive locale confirmée [46], [47], [48], [49], [50], [51], [52], [53]. Ces traitements basés sur l’altération physique

Conclusion

Les traitements non chirurgicaux du cancer de prostate : traitements anti-androgéniques, radiothérapie, curiethérapie, inhibiteurs de la 5 alpha réductase… entraînent des modifications qui peuvent prendre au dépourvu un pathologiste non averti et avoir des conséquences redoutables pour la prise en charge thérapeutique du patient : surestimation du score de Gleason, non-évaluation d’une marge positive, faux diagnostic de prostatectomie blanche (pT0)… Il est donc indispensable que l’urologue

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Cited by (10)

Oncological and functional results of robotic salvage radical prostatectomy after permanent brachytherapy implants
2017, Cancer/Radiotherapie
Citation Excerpt :
However, positive biopsies less than 24 months after brachytherapy have no prognostic value [18]. Finally, modifications seen in the tissues after brachytherapy make the interpretation of new biopsies very difficult [19]. This might explain the “subgrading” observed in our study for the new biopsies and explain the differences between the biopsy analyses and prostatectomy.
To evaluate the feasibility of robotic salvage prostatectomy for local recurrence after permanent brachytherapy implants for prostate cancer.
Seven patients were operated by robotic salvage prostatectomy with or without pelvic lymph node dissection between October 2007 and March 2012, for a local recurrence after iodine 125 permanent brachytherapy implants. Local recurrence was proved by prostate biopsies, once biochemical relapse was diagnosed and imaging assessment performed.
The average age of a patient at the time of diagnosis was 66 years (62–71 years). The median nadir prostate specific antigen (PSA) serum concentration after brachytherapy was 1.29 ng/mL (0.6–2.1 ng/mL), obtained after a median of 12 months (7–21 months). The average [PSA] before robotic salvage prostatectomy was 6.60 ng/mL (4.17–13.80 ng/mL). [PSA] at 1 and 3 months after prostatectomy was less than 0.05 ng/mL in five patients. [PSA] remained below 0.05 ng/mL for six patients at 12 and 24 months. One month after robotic salvage prostatectomy, all patients had at least partial urinary incontinence. At 12 and 24 months after robotic salvage prostatectomy four patients have regained full urinary continence. In terms of erectile function at 24 months, three patients retained erectile function with possible sexual intercourse.
Robotic salvage prostatectomy appears to be a reliable treatment in terms of oncological outcome with convincing results both for urinary continence and erectile function for selected patients with local recurrence after permanent brachytherapy implants.
Évaluer la faisabilité d’une prostatectomie de rattrapage robotisée pour une rechute locale après une curiethérapie de prostate initiale par implants permanents.
D’octobre 2007 à mars 2012, sept patients pris initialement en charge par curiethérapie de prostate par iode 125, en situation de rechute locale, ont bénéficié d’une prostatectomie robotisée avec ou sans curage pelvien ganglionnaire. Les patients étaient en situation de rechute biologique selon la concentration sérique de d’antigène spécifique de la prostate et avaient eu un bilan d’imagerie complet. Le diagnostic de rechute locale a été confirmé par les biopsies prostatiques.
L’âge moyen des patients au moment du diagnostic était de 66 ans (62–71). Le nadir médian de la concentration sérique de d’antigène spécifique de la prostate à un an de la curiethérapie était de 1,29 ng/mL (0,6–2,1 mg/mL). La concentration moyenne d’antigène spécifique de la prostate lors du traitement de rattrapage par prostatectomie robotisée était de 6,60 ng/mL (4,17–13,80 ng/mL). La concentration sérique de d’antigène spécifique de la prostate était à 1 et 3 mois de la prostatectomie de moins de 0,05 ng/mL pour cinq patients. À 12 et 24 mois, elle est restée inférieure à 0,05 ng/mL pour six patients. Un mois après la chirurgie, tous les patients souffraient d’une incontinence urinaire partielle. À 12 et 24 mois, cinq patients avaient une continence parfaite. Pour ce qui concerne la fonction érectile, à 24 mois, trois patients ont conservé une fonction érectile permettant les rapports.
La prostatectomie de rattrapage robotisée réalisée pour des patients sélectionnés en situation de rechute locale après curiethérapie est une option thérapeutique à considérer, avec des résultats fiables et des résultats fonctionnels probants en termes de continence et de conservation érectile.
Delineating biochemical failure with <sup>68</sup>Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer
2017, Radiotherapy and Oncology
Citation Excerpt :
Non-functional pelvic MRI is sub-optimal in identifying a local recurrence if the PSA is less than 10 [8], and is not routinely performed for a biochemical recurrence. The interpretation of biopsy following EBRT may be associated with a high false positive rate and requires an experienced pathologist [9]; in addition, there is no consensus as to the appropriate timing of biopsy. Furthermore, local recurrence on biopsy does not exclude regional or distant disease.
We investigated the role of ⁶⁸Ga-PSMA-PET (PSMA) to determine the location of disease recurrence in those with a rising PSA following definitive external beam radiation treatment (EBRT).
538 men were treated with image guided EBRT to a dose of 78 or 82 Gy between 2007 and 2014. Patients at least 24 months post EBRT with biochemical failure (nadir + 2) underwent PSMA scanning. Local recurrence (LR) was defined as increased uptake within the prostate or seminal vesicles. Distant disease included lymph node (LN), bone or visceral metastases.
419 men formed the study cohort. Median follow-up was 50 months, 70 patients (17%) had biochemical failure (BF), 13 of whom have died. Of the 57 survivors, 5 had metastases detected on conventional scans; 2 were lost to follow up. 48 men (of 50 candidates) underwent PSMA; in all cases, the PSMA was unequivocally positive.
Of the 48 positive scans, 25 patients (52%) failed beyond the prostate – 5 in bones, 16 LN, 3 in both, and 1 in the lungs. Fifteen men (31%) failed within the gland and in either LN (11), bones (3), or both (1). Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2 years.
PSMA was positive in all patients with BF. Site of failure following dose-escalated EBRT was generally distant. Isolated LR (on PSMA) occurred in only 8 of 419 patients post-EBRT.
Analysis and prognostic factors of the specimen of radical prostatectomy in prostate cancer
2015, Progres en Urologie
La prise en charge des pièces de prostatectomie totale et leur analyse histopathologique sont essentielles pour confirmer le diagnostic et évaluer l’histo-pronostic des cancers de la prostate.
Une revue de la littérature a été effectuée à partir de la base de données PubMed, en privilégiant les articles récents (5 ou 10 dernières années), à partir des mots clés suivants : prostate cancer ; prostatectomy ; specimen ; handling ; pathology ; tumor staging ; Gleason score ; surgical margin ; prognosis ; frozen section ; lymph node ; biomarkers. Une attention particulière a été portée sur la prise en charge des prélèvements et la caractérisation des critères histo-pronostiques.
La prise en charge des pièces de prostatectomie totale et des produits de curage ganglionnaire est actuellement standardisée selon des critères internationaux. L’évaluation des facteurs histo-pronostiques principaux, que sont le score de Gleason, le stade pathologique et le statut des limites d’exérèse, a beaucoup évoluée ces dernières années permettant une prédiction accrue du risque de récidive après traitement chirurgical.
La standardisation de la prise en charge et du compte rendu anatomopathologique de la prostatectomie totale représente un préalable à l’uniformisation des approches thérapeutiques. Cette standardisation a un rôle crucial dans la stratification des malades atteints d’un cancer de la prostate et la personnalisation du traitement.
Handling and pathologic analysis of radical prostatectomy specimens are crucial to confirm the diagnosis of prostate cancer and evaluate prognostic criteria.
A systematic review of the scientific literature was performed in the Medline database (PubMed), using different associations of the following keywords: prostate cancer; prostatectomy; specimen; handling; pathology; tumor staging; Gleason score; surgical margin; prognosis; frozen section; lymph node; biomarkers. A particular search was done on specimen management and characterization of tissue prognostic factors.
Handling of both radical prostatectomy specimen and lymph node dissection is standardized according to international criteria. Although the main histoprognostic factors are still Gleason score, pathologic staging and margin status, these criteria have been refined these last 10 years, allowing to improve the prediction of relapse after surgical treatment.
The standardization of handling and pathology reporting of radical prostatectomy specimens will be mandatory for treatment uniformization according to risk stratification in prostate cancer and personalization of therapeutic approaches.
Management of prostate cancer recurrence after definitive radiation therapy
2010, Cancer Treatment Reviews
Citation Excerpt :
Also, transrectal prostate needle biopsies at the time of BR should be obtained to confirm local disease before considering salvage treatment. As discussed earlier, biopsies should be analyzed by a pathologist who is familiar with RT effects on prostatic tissue.28 Cheng et al. reported a Gleason score < or =6 to predict for a better prognosis after salvage RP.92
The management of prostate cancer (PC) recurrence after definitive radiation therapy (RT) is shifting and there is no consensus regarding the optimal strategy. The major challenge is determining the anatomical site of relapse. In case of biochemical relapse (BR), androgen deprivation therapy (ADT) is a non-curative option commonly used, while patients with a local PC recurrence could be managed through a curative intent. Based on a Pubmed data search, this manuscript focused on the management of post-RT local PC recurrences. In case of BR (nadir + 2 ng/ml), classical imaging work-up is not contributive for PSA levels <10 ng/ml while new imaging investigations (diffusion MRI, 11C-choline PET) are more sensitive to detect local and distant recurrences at lower PSA levels. Positive prostate biopsies are the only method for confirming local recurrence, although this technique presents limitations. Primary PC presentation as well as PSA-related features (interval to failure, PSA kinetic) and patient features (life expectancy, urinary, sexual status) are important to consider. Results of curative salvage options (radical prostatectomy, cryotherapy, brachytherapy and high-intensity focused ultrasound-HIFU) are analyzed and discussed. Each of these therapies appears feasible and has its own set of experience and toxicity profile. Other therapeutic options (photodynamic therapy, ADT, observation) are discussed. Longer follow-up and mature series are needed to evaluate the optimal strategy and prospective trials are warranted. Each clinical situation should be discussed in a multidisciplinary setting. Different options should be explained to the patient and decision should be taken after balancing treatment outcomes with life expectancy.
The effect of lymph node dissection on cancer-specific survival in salvage radical prostatectomy patients
2021, Prostate
Biochemical recurrence after radiation therapy
2018, Prostate Cancer: Clinical Case Scenarios

View all citing articles on Scopus

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Résumé

Summary

Section snippets

Traitements conservateurs du cancer de prostate

Traitement hormonal et prostate

Modifications post-radiques

Chimiothérapie

Autres traitements

Conclusion

Eur Urol

Ann Oncol

Eur J Cancer

Clin Prostate Cancer

J Urol

J Urol

Urology

Urol Clin North Am

Urology

J Urol

J Urol

Urology

Urology

J Urol

Eur Urol

Leuprorelin acetate in prostate cancer: a european update

Int J Clin Pract

Radiation injury of the normal and neoplastic prostate

Am J Surg Pathol

Histopathological effects of androgen deprivation in prostatic cancer

Semin Urol Oncol

Modifications histologiques de la prostate normale et cancéreuse après traitement (hormonothérapie et radiothérapie) et leurs conséquences sur l’interprétation du score de Gleason

Prog Urol

Un grade tumoral est-il applicable au cancer de la prostate sous finastéride ?

Prog Urol

Histopathological changes induced by therapies in the benign prostate and prostate adenocarcinoma

Histol Histopathol

Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-beta receptor expression

Prostate

The effects of the dual 5alpha-reductase inhibitor dutasteride on localized prostate cancer–results from a 4-month pre-radical prostatectomy study

Prostate

Flutamide in men with prostatic intraepithelial neoplasia: a randomized, placebo-controlled chemoprevention trial

Am J Ther

Early effects of pharmacological androgen deprivation in human prostate cancer

Br J Urol Int

Apoptosis in prostate carcinomas after short-term treatment with decapeptyl

Ann NY Acad Sci