FOIU 2018: Aggressive and Unusual Subtypes of Prostate Cancer

Tel-Aviv, Israel ( Jonathan Epstein, MD gave a talk on the aggressive and unusual subtypes of prostate cancer. 

His first topic was prostatic duct adenocarcinoma, which may arise in large periurethral ducts and project into the urethra around the verumontanum, clinically mimicking urothelial carcinoma. Patients usually present with LUTS and hematuria, and the diagnosis is usually made on TURP. It can also arise in secondary peripheral ducts and may present as ordinary (acinar) adenocarcinoma with abnormal DRE or elevated serum PSA levels, and diagnosed on needle biopsy. This type of tumor is graded as:

  • PIN like Ductal: Gleason pattern 3
  • Cribriform or papillary or ductal, graded as Gleason pattern 4
  • With central necrosis: Gleason pattern 5
For stage, there is a similar prognosis compared to the usual acinar prostate cancer (PC). 

Intraductal carcinoma (IDC) was discussed next, which is frequently adjacent to Gleason pattern 4 invasive carcinoma. Definitive therapy is recommended in men with IDC on needle biopsy, even in the absence of pathologically documented invasive prostate cancer. IDC is more frequently seen with Gleason pattern 4-5. It has also been shown to be an independent prognosticator of early biochemical relapse and metastatic failure.1Moreover, it is predictive of cancer-free survival even in a subset of men with Gleason score >=8. 2 IDC is also associated with rapid progression of castrate-resistant prostate cancer (CRPC), and It is associated with poor response to initial androgen deprivation therapy (ADT) and sequential docetaxel-based chemotherapy. Abiraterone has shown a better therapeutic response than docetaxel as a first-line therapy in IDC metastatic CRPC patients.

IDC has distinct morphology when compared to high-grade PIN (HGPIN). It is associated with high-grade cancer and adverse pathology at surgery and a relatively poor prognosis. In most cases, it is an advanced type of tumor progression with the intraductal spread of the tumor, and rarely an in-situ high-grade cancer. Epstein commented that it is justifiable to treat patients with IDC, even if they do not have infiltrative prostate cancer.

Next, PC with neuroendocrine differentiation was discussed by Epstein. This entity of small cell carcinoma is usually diagnosed at an advanced stage, with >90% being diagnosed at stage T3-T4. There is evidence of a prior diagnosis of adenocarcinoma in 14-35% of cases with a median time of 18-50 months from diagnosis. At the time of diagnosis of small cell cancer, it is found either in its pure form in 70% of cases, or in its mixed form with ‘standard’ adenocarcinoma in 30% of cases. There is no difference between these two forms with regards to the prior history of adenocarcinoma. 

Following the onset of small cell cancer, median survival is around 5-17.5 months. It is common to have widespread metastases, mostly composed of small cell carcinoma. It is not uncommon for PC Gleason score 10 (5+5) to be misdiagnosed as small cell carcinoma when stains for neuroendocrine markers are performed. 

Epstein next discussed the variant of Anaplastic PC, which needs to have one of the following criteria:

  • Histologic evidence of small cell PC (25.4%)
  • Exclusively visceral metastases (16.7%)
  • Radiographically predominant lytic bone metastases (14%)
  • Bulky (5 cm) lymphadenopathy or Gleason 8 tumor mass in the prostate pelvis (43%)
  • Low PSA (<10 ng/ml) at initial presentation (before ADT or at symptomatic progression in the castrate setting) plus high volume (>=20) bone metastases (22.8%)
  • Presence of neuroendocrine markers on histology (positive staining with chromogranin A or synaptophysin) or in serum (abnormal high serum levels for chromogranin A or GRP) at initial diagnosis or at progression. This needs to be accompanied by any of the following in the absence of any other cause (18.4%):
  1. Elevated serum LDH
  2. Malignant hypercalcemia
  3. Elevated serum CEA
  • Short interval (<=6 months) to androgen-independent progression following the initiation of hormonal therapy
The recommended treatment needs to be identical to that of small cell carcinoma.

Lastly, Epstein discussed sarcomatoid carcinoma (carcinosarcoma). In these cases, there is a prior history of PC in 66-78% of cases, with an interval ranging between 6 months and 16 years (median of 7 years). The adenocarcinoma can be variable with either ductal, small cell, or squamous. Another rare possible variant in this setting is the Spindle variant, featuring bizarre giant cells, osteosarcoma, chondrosarcoma, or rhabdomyosarcoma.

Epstein summarized his talk, stating that rich and diverse range of histological variants of PC exists, with not only unique histological features but also with unique clinical and treatment implications.

1. T.Van der Kwast et al. European Journal of Cancer 2012
2. Tao Zhao et al. The prostate 2014

Presented by: Jonathan Epstein, MD, Department of Pathology, Johns Hopkins Hospital, Baltimore, Maryland, USA

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan  at the 2018 FOIU 4th Friends of Israel Urological Symposium, July 3-5. 2018, Tel-Aviv, Israel