M0 progression prostate cancer

AUA 2025

Dr. Henderson noted that prostate cancer remains the 2nd most frequently diagnosed cancer annually in men, accounting for 7.3% of all incident tumors worldwide. Following primary therapy, approximately 30% of men will experience biochemical recurrence, and >30% will be found to have metastases at the time of biochemical recurrence.

How is biochemical recurrence defined? Various PSA cut-offs have been defined, based on the primary therapy received:

• Post-radical prostatectomy: Rising PSA >0.2 ng/ml
  • PSA persistence: Failure of PSA to decline below 0.1 ng/ml following a radical prostatectomy
• Post-external beam radiotherapy: A PSA rise >2 ng/ml above nadir

While current guidelines lack consensus regarding the optimal management of biochemically recurrent prostate cancer patients, they all agree on the following key principles:

• Consider a patient’s life expectancy
• Risk stratifying patients is critical
• Low-risk biochemical recurrence: Observation may be considered
  • EAU definition: PSA doubling time (PSADT) >1 year and presence of pathologic Grade Group <4 disease on the radical prostatectomy specimen
• High-risk biochemical recurrence: Timely salvage treatment should be considered
• EAU definition: PSADT <1 year or presence of pathologic Grade Group 4–5 disease on the radical prostatectomy specimen

• For patients with high-risk biochemical recurrence, Dr. Henderson highlighted the following treatment options:

  • External beam radiotherapy (EBRT) +/- ADT
  • ADT +/- non-steroidal anti-androgen (NSAA)
    • Continuous or intermittent
  • Salvage radical prostatectomy in select, fit patients with prostatic fossa-limited disease
  • High-intensity focused ultrasound (HIFU)
  • Cryotherapy

  Dr. Henderson concluded his presentation with the following take home messages for the management of biochemically recurrent prostate cancer patients:

• Risk stratify each patient
• Consider a patient’s estimated life expectancy
• Shared decision making between patients and physicians is critical
• Consider clinical trial enrolment, where available

Reference: Management of M0 progression after RT

Reference: Management of M0 progression after surgery

Unexplained cytopenias management

 April 2025 Blood journal

Cytopenia of any lineage: SPEP, CRP, RA, ANA, anti ds DNA, C3, C4, HIV, CMV, EBV, Hep B, C, anti parvovirus B19, SARS-CoV-2

Isolated anemia: haptoglobin, erythropoietin, uric acid, Hb electrophoresis,  DAT and indirect Coomb's

Isolated neutropenia: Flow cytometry, ANCA

Isolated thrombocytopenia: APLA testing, H pylori, plt in sodium citrate

Severe pancytopenia differential:

• malignancy like AML 
• MDS, 
• rheumatologic
• drug toxicity 
• infectious/viral
• nutritional

• immune dysregulation
•  inherited bone marrow failure
•  aplastic anemia

1. Chronic idopathic neutropenia: isolated neutropenia,  middle aged women. BMBx needed. Uncomplicated. Low risk of transformation.

2.  ICUS: at least one lineage affected ie. Hb < 11 or ANC < 1500 or plt < 100K. Bmbx needed. No proof of clonality needed. Variable course and risk of transformation.  Repeat work up and continued surveillance needed.

3. CCUS: bmbx needed, persistent unexplained cytopenia, non MDS somatic mutation,  higher risk of progression to malignancy than ICUS or CIN.

4. CCMUS: (persistent monocytosis plus CCUS > 0.5), 1 myeloid mutation of at least VAF 2%,  no dysplasia, not meeting criteria for CMML

5. CHIP: no unexplained cytopenia, but myeloid driver mutation, no MDS defining cytogenetic abnormality. Can be seen in inflammatory disorders. Increased risk of cardiovascular abnormalities.

6. CH in aplastic anemia: bm cellularity less than 25%. Somatic mutation in non MDS myeloid driver or non MDS defining cytogenetic aberration.

7. VEXAS syndrome: autoimmune manifestations, UBA1 somatic mutation, no MDS defining genetic abnormality

Clonal hematopoiesis risk score

Multivariable analysis 

 single DNMT3A mutations,

 high-risk mutations, 

two or more mutations,

 a VAF of 0.2 or more, 

65 years of age or older, 

having CCUS versus CHIP, 

and red blood cell indices, influenced MN risk in a variable direction. CHRS was used to define low-risk (n=10,018 [88.4%]), intermediate-risk (n=1196 [10.5%]), and high-risk (n=123 [1.1%]) groups. In clinical cohorts, most MN events occurred in high-risk patients with CHIP/CCUS.

DNMT3A, TET2, and ASXL1 mutations were the most commonly mutated genes in CHIP/CCUS 

Mutations in splicing factor: SRSF2, SF3B1, ZRSR2 and AML like genes- IDH1/IDH2, FLT3 , RUNX1 and TP53 are high risk.

Increased RDW and high MCV are risk factors too

General approach: rule out infection, vit def, autoimmune condition or non clonal bone marrow issue like aplastic anemia. Clonal process can be MDS, AML, PNH Then get a bmbx to see if clonality identified. If clonality identified close monitoring to see if they progress. If no clonality, evaluate alternate causes.

In patients with ICUS, look for inherited mutations. DDX41 is the most common associated with late malignant potential.

Pregnancy and breast cancer

 Pearls

• Anthracyclines are safe and should be done q 3 weeks not DDAC
• Taxanes are now considered safe, but may need higher doses due to placental breakdown
• Platinum agents are safe, but low albumin levels can lead to toxicity
• 5FU and xeloda safe, but no clear role in pregnancy
• Contraindicated in pregnancy and lactation: trastuzumab, ADC, PARP inhibitor, methotrexate( pregnancy)
• Endocrine therapy is contraindicated
• Supportive care: Reglan ( safe) promethazine ( safe), olanzapine for highly emetogenic regimens. Dexamethasone can cross the placenta and affect fetal head growth ( short term use ok).
• Insufficient data re: safety of bisphosphonates, CDK4/6 inhibitor HER 2 TKI, IO, use of growth factors

Radiation: contraindicated

When to resume chemo post delivery: 

• 2 weeks after vaginal delivery and 4 weeks after C section. 
• Use DVT prophylaxis with lovenox for 6 weeks