Clinical-Prostate cancer
Feasibility and outcome of radical prostatectomy following inductive neoadjuvant therapy in patients with suspicion of rectal infiltration

https://doi.org/10.1016/j.urolonc.2021.07.028Get rights and content

Highlights

  • Neoadjuvant systemic treatment is effective for local tumor downsizing in rectum-infiltration cT4 prostate cancer patients.

  • Radical prostatectomy after neoadjuvant systemic treatment is feasible in initial inoperable cT4 rectum-infiltrating PCa tumor.

  • Both digital rectum examination and mpMRI should be included in a setting of neoadjuvant tumor downsizing to exclude ongoing rectum infiltration.

  • Complications and failure rates in initially inoperable rectum-infiltrating PCa patients undergoing RP after neoadjuvant treatment tend to be higher, yet justifiable in this patient cohort, compared to lower cT-stages.

Abstract

Objective

To determine the feasibility and outcome of radical prostatectomy (RP) following neoadjuvant therapy (NAT) in patients with initial inoperable, rectum-infiltrating cT4 prostate cancer (PCa).

Methods

From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating PCa at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database. Two patients were still inoperable after NAT. Downsizing was administered for at least 20 weeks and RP was performed after excluding ongoing rectal infiltration.

Results

At diagnosis, median PSA was 42.5 ng/ml (IQR: 23.0–66.1). Inductive NAT consisted of androgen deprivation therapy (ADT) in combination with chemotherapy (n = 9) or without chemotherapy (n = 14). Median preoperative PSA was 0.93 ng/ml (IQR: 0.24–0.40). Median time from NAT to RP was 6 months (IQR: 5–7). Two patients were still inoperable after NAT. Of 24 patients undergoing RP, abortion of surgery due to inoperability was observed in 2 patients (8.4%), demonstrating a total failure rate of NAT in 4 out of 26 patients (15.4%). One patient suffered a rectal injury with consecutive colostomy (4.2%). No Clavien-Dindo complication Grade IV or V were observed. Urinary continence was achieved in 16 patients (84.2%). Sufficient erection for sexual intercourse was present in 2 patients (10.5%). All patients received adjuvant ADT with or without radiation therapy. Median PSA at 13 months was 0.08 ng/ml (IQR: 0.01–0.74).

Conclusion

RP of initially rectum infiltrating PCa is feasible and safe after inductive NAT, however complications rates tend to be higher compared to standard RP.

Introduction

According to current guidelines neoadjuvant androgen deprivation therapy (ADT) for prostate cancer (PCa) is not recommended as standard clinical practice prior to radical prostatectomy (RP) [1,2]. Following a Cochrane-review by Kumar et al. in 2006, NAT was associated with a decrease in pT3-stage and decrease of positive surgical margins. However, neither prostate specific antigen (PSA) relapse-free survival nor cancer specific survival improved significantly in this study [3]. Irrespectively to the disputable long-term cancer-specific outcome of neoadjuvant treatment, it is known that neoadjuvant treatment for PCa can result in tumordownsizing and potential downstaging [4,5]. However, patients being diagnosed with initial cT4-stage PCa with a suspicicous rectal infilitration have in the past been more likely to be considered inoperable, due to fear of higher complication rates, such as rectal injury with a need of colon-stoma planting or development of fistulas [6,7]. Conversely, radiotherapy in such patients is associated with high risk of fistula and side effects. Refusing to operate these patients undisputable narrows the spectrum of ongoing treatment modalities - this holds even more true in light of ongoing inverse stage migration trend [8,9]. Besides possible local complications due to tumor progress emerging data empahsizes, that local therapy – even in low-volume metastatic PCa - might be beneficial for oncological long-term results [10,11]. Tilki et al. recently demonstrated that patients form a very high risk PCa cohort benefit most from maixmum treatment – defined as a sequence of RP, External beam radiation therapy (EBRT) and ADT - in terms of PCa-specific mortality and all cause mortality [12]. In order to enable primarly inoperable PCa patients the maximum treatment possible, NAT represents a promising treatment modality to downsize local tumor burden. Little is known about perioperative compliactions and short-term functional outcomes in this subgroup of patients [4]. The aim of the present study was to evaluate feasability, safety and outcome of RP in patients with initial cT4 PCa and NAT with ADT and with or without chemotherapy.

Section snippets

Study population

From 01/2018 to 12/2020, 26 patients with clinical (DRE) or radiographical (mpMRI) suspicion of rectum infiltrating prostate cancer at diagnosis and NAT prior to RP were retrospectively identified from our prospective institutional database for further analyses. Moreover, 2 patients were still inoperable after NAT. (Preoperative) staging was done according to EAU guidelines [1]. Patients with a non-relocatable rectal mucosal tissue-layer and fixed tumor-mass were defined as primarily inoperable

Preoperative characteristics

Excluding 2 patients, which harbored persistent ongoing rectal infiltration in DRE and mpMRI symbolizing an unsuccessful neoadjuvant downsizing, a total of 24 patients were included in the study. Median age at diagnosis was 63 years (IQR: 57.5–70), median PSA at 42.5 ng/ml (IQR: 23.0–66.1). No patient harbored WHO/International Society of Urological Pathology (ISUP) grade group 1 at biopsy, 2 (8.3%) patients harbored ISUP 2, 4 (16.7%) harbored ISUP 3, 2 (8.3%) harbored ISUP 4 and 16 patients

Discussion

Current literature lacks of information regarding feasibility and outcome of RP following inductive NAT for initial, inoperable rectal infiltrating PCa. We analyzed our institutional database in a retrospective approach in this rare PCa cohort to address this void.

First, we could demonstrate that NAT is for the most part effective in downsizing initial rectal infiltration PCa before undergoing RP. Except for 2 patients, which presented with a persistent, profound rectal infiltration in DRE and

Conclusion

RP of initially rectum infiltrating PCa is feasible and safe after inductive, NAT, however complications rates tend to be higher and both DRE and radiological imaging should be taken to hand before deciding to undergo RP. Further prospective studies should be performed in order to elucidate the appropriate type and dosage of NAT.

Authors’ contributions

Benedikt Hoeh: Manuscript writing, project development. Felix Preisser: Data analysis, manuscript editing. Mike Wenzel: Data analysis, manuscript editing. Clara Humke: Data analysis. Clarissa Wittler: Data collection. Jens Köllermann: Manuscript editing. Boris Bodelle: Manuscript editing. Simon Bernatz: Manuscript editing, protocol development. Thomas Steuber: Data analysis, manuscript editing. Derya Tilki: Data analysis, manuscript editing. Markus Graefen: Data analysis, manuscript editing.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

The authors have no relevant financial interests to disclose.

Ethics approval

All patients had given written consent and the study was approved by the local institutional review boards of the University Cancer Centre and the local Ethical Committee.

Availability of data and material

All datasets generated for this study are included in the manuscript.

Code availability

Software R statistics (version 3.6.1).

References (29)

  • N. Mottet Chair, P. Cornford Vice-chair, R.C.N. van den Bergh, E. Briers Patient Representative, M. De Santis, S....
  • Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Interdisziplinäre Leitlinie der...
  • Kumar S, Shelley M, Harrison C, Coles B, Wilt TJ, Mason MD. Neo-adjuvant and adjuvant hormone therapy for localised and...
  • Hajili T, Ohlmann CH, Linxweiler J, Niklas C, Janssen M, Siemer S, et al. Radical prostatectomy in T4 prostate cancer...
  • Zhang L, Zhao H, Wu B, Zha Z, Yuan J, Feng Y. The impact of neoadjuvant hormone therapy on surgical and oncological...
  • Mandel P, Linnemannstöns A, Chun F, Schlomm T, Pompe R, Budäus L, et al. Incidence, risk factors, management, and...
  • Barashi NS, Pearce SM, Cohen AJ, Pariser JJ, Packiam VT, Eggener SE. Incidence, risk factors, and outcomes for rectal...
  • Budäus L, Spethmann J, Isbarn H, Schmitges J, Beesch L, Haese A, et al. Inverse stage migration in patients undergoing...
  • Hoeh B, Preisser F, Mandel P, Wenzel M, Humke C, Welte M-N, et al. Inverse stage migration in radical prostatectomy-a...
  • Parker CC, James ND, Brawley CD, Clarke NW, Hoyle AP, Ali A, et al. Radiotherapy to the primary tumour for newly...
  • Dai B, Zhang J, Wang H, Wang Q, Kong Y, Zhu Y, et al. 618MO Local therapy to the primary tumour for newly diagnosed,...
  • Tilki D, Chen M-H, Wu J, Huland H, Graefen M, Braccioforte M, et al. Surgery vs radiotherapy in the management of...
  • Kyriakopoulos CE, Chen Y-H, Carducci MA, Liu G, Jarrard DF, Hahn NM, et al. Chemohormonal therapy in metastatic...
  • Preisser F, Theissen L, Wild P, Bartelt K, Kluth L, Köllermann J, et al. Implementation of intraoperative frozen...
  • Cited by (7)

    View all citing articles on Scopus
    #

    Contributed equally to this work.

    View full text