LAUSR

A 58-year-old man, was diagnosed with prostate cancer (PCa) in 2004, following an elevated PSA level of 8 ng/mL and an abnormal DRE. The biopsy confirmed an adenocarcinoma of the prostate, Gleason Grade Group 2, on all biopsy cores in the left prostatic lobe. Radical prostatectomy (RP) and androgen-deprivation therapy (ADT) associated with radiotherapy were initially declined by the patient who was asymptomatic and sexually active. The patient made an unilateral decision to receive treatment only when symptomatic. At 9 years later, the PSA level was 80 ng/mL, the patient became symptomatic with voiding LUTS and dysuria, and a local progression staged at T4, affecting bladder neck, rectum, but without lymph node or metastasis on CT and bone scans. A palliative TURP was performed, and the patient agreed to be treated by ADT (GnRH analogue). The PSA level dropped to 30 ng/mL, but subsequently increased rapidly over the following year to reach 272 ng/mL, the testosterone was <50 ng/dL, and the tumour progressed to the perineum, with rectal dyskinesia and an important subcutaneous mass causing major discomfort when sitting. There was sufficient rectal occlusion to warrant bowel cutaneous diversion. CT (Fig. 1) and bone scan remained negative for lymph node or metastatic involvement. The patient was referred to our department for further management. He agreed to be treated by extensive surgery including palliative intestinal and urinary diversion (Bricker) with maximum tumour removal (cysto-vesiculeprostato-protectomy). In 2015 (aged 69 years), a total pelvic exenteration with iliac lymphadenectomy was performed, with perineal excision involving the skin that was invaded by the tumour. Pathological examination showed a pure mucinous prostatic adenocarcinoma, classified as Gleason Grade Group 4 (Gleason score 4 + 4; Fig. 2). Immunohistochemistry (IHC) showed positive staining for homeobox B13 (HOXB13) and prostate-specific membrane antigen (PSMA) confirming the prostate origin of the tumour. We also undertook IHC for KI67 proliferation antigen (MIB-1) and DNA mismatch repair (MMR) genes. The proliferation rate was high with 10% of cells positive for MIB-1 staining. IHC for MMR proteins found positive expression of MutL homolog 1 (MLH1) and PSM2, but negative expression of MutS homolog 2 (MSH2) and MSH6 indicating a mismatch DNA repair deficiency. In addition, we observed lymphocytes infiltration around the tumour, with positive staining of CD3 and CD8 in the stromal tissue. Expression of programmed death-ligand 1 (PD-L1) was negative in the tumour, with only weak programmed death 1 (PD-1) expression around the tumour.