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Biochemical recurrence

Overview:

  • 30 – 50 % of patients will develop a rising PSA after surgery or radiation
  • A detectable or rising PSA often does not lead to clinically apparent disease
  • 15 – 35 % of patients require further treatment

 

Definition after surgery:

  • AUA: PSA > 0.2 ng / mL confirmed on two consecutive tests
  • EAU: PSA > 0.4 ng / mL and rising best predicts further metastases

 

Definition after radiation (Phoenix criteria)

  • PSA increase > 2 ng / mL above the post radiotherapy nadir

 

Patients with biochemical recurrence are a heterogenous group – some are destined to lethal prostate cancer recurrence, and some will never need any further treatment and live long lives.

Therefore, recommended to stratify to low or high risk groups proposed by EAU and validated:

 

Imaging for biochemical recurrence:

There is limited data as to the utility of imaging and whether changing practice based on imaging (particularly PSMA PET) improves outcomes.

Bone scan / CT

  • Diagnostic yield is low in asymptomatic patients
  • Only 5 % of bone scans are positive when PSA is < 7.0 ng / mL
  • Only 11 – 14 % will have a positive CT

 

PSMA-PET

  • Much more sensitive at detecting metastases with BCR
  • 33 % at PSA < 0.2
  • 45 % at PSA 0.2 – 0.49
  • 59 % at PSA 0.5 – 0.99
  • 95 % at PSA > 2.0
  • PSMA-PET has shown that many post-surgical recurrences occur outside the prostatic fossa, even at low PSA levels.

MRI

  • May detect local recurrences after surgery but with poor sensitivity < 0.5 ng / mL
  • Useful in detecting local recurrence in prostate after radiation, and can aid with biopsy targeting

 

EAU guidelines for imaging in BCR:

  • Perform PSMA if the PSA is > 0.2 ng / mL after surgery and results will influence treatment decision, and in patients fit for curative salvage treatment after radiotherapy

 

Salvage radiation after surgery

As above – “early salvage” radiation is preferred to adjuvant in most circumstances, except for very high risk disease (2 of pT3, PSM, Gl 8+) in which case adjuvant may be offered.

Salvage radiation has been shown in retrospective meta-analyses to be favourable for OS and CSS (compared to observation) – particularly for patients with rapidly rising PSA and with PSA > 0.4 ng / mL.

Potential issues with salvage radiation:

  • Some patients with very slowly rising PSA or low risk are unlikely to benefit from salvage radiation
  • PSMA PET is now detecting first evidence of recurrence outside the field of salvage radiation – management of these patients (who would previously have been treated with pelvic radiation) is unclear

EAU guidelines for salvage radiation:

  • Consider monitoring only for EAU low risk patients with BCR post surgery
  • Offer hormonal therapy with salvage radiation
  • Once the decision for salvage radiation has been made, give at least 64 Gy ASAP
  • A negative PSMA-PET should not delay salvage radiation if it is otherwise indicated

 

What do I do:

  • Monitor until 0.2 ng / mL and then discuss salvage radiation, perform PSMA PET and offer radiation oncology referral +/- PSMA PET – especially in high risk patients
    • If PSMA PET negative – still offer salvage radiation
  • Consider ongoing surveillance in low risk patients, or patients with continence issues.

 

Metastasis detected therapy based on PET

Retrospective studies have suggested a benefit in CSS for metastasis directed nodal therapy (SABR or salvage LND)

  • There is no prospective evidence so this should still probably be considered experimental

Salvage lymph node dissection has a poor evidence base and low rates of 5 year BCR free survival – it should be seen as an attempt to delay systemic therapy as opposed to a cure.

 

PSA failure after radiation

Options include:

  • Watch and wait
  • ADT (if PSA-DT < 12 months)
  • Salvage radical prostatectomy
  • SABR re-irradiation
  • Salvage brachytherapy
  • HIFU or cryotherapy

The evidence for all salvage local treatments is reasonably low quality.

Prostate biopsy should be performed 18 months after radiation as cancer kill can take a while. Biopsy should be considered mandatory before subjecting to salvage treatments. PSMA/MRI can be helpful.

 

Salvage radical prostatectomy:

Should only be considered in patients with low co-morbidity, life expectancy > 10 years, PSA recurrence < 10, no evidence of extra-prostatic disease, and preferably those with relatively low risk features pre-radiation (Gleason 7, cT1/2).

  • Multi-centre analysis – 5 year BCR free 56 % ; 5 year cancer specific survival 97 %
  • Anastomotic stricture 47 % vs 5 %
  • Retention 25 % vs 3 %
  • Fistula 4 % vs < 0.1 %
  • Abscess 3 %
  • Rectal injury 9 %
  • ED universal
  • Incontinence 20 – 90 % (? 50 %)

 

Other salvage options:

Salvage brachytherapy (HDR or LDR)

  • Appears to be effective (5 yr BCR free survival 50 – 60 %) with acceptable toxicity, but published series are small

Salvage SABR

  • Six fractions of 6 Gy / total 36 Gy – 3 yr BCR free survival 55 %, more urinary toxicity

HIFU / Cryo

  • Experimental

ADT

  • Aiming to delay metastases, improve quality of life and overall survival – consider if rapid doubling time

Watch and wait

  • Particularly if < 10 year life expectancy, EAU low risk BCR, or unwilling to undertake salvage treatment