Solid organ transplant recipients (SOTRs) can have between a 2 to 3 times higher risk of developing certain cancers including non-Hodgkin lymphoma (NHL), colorectal cancer (CRC), lung cancer, and kidney cancer.1 This has led many physicians to alter their cancer screening protocols in SOTRs, including in prostate cancer (PC), even though the data in this unique patient population are not as clear as they are in other malignancies.1,2

Hall and colleagues reviewed 164,156 SOTRs in the United States between 2000 and 2008 and found a total of 350 cases of prostate cancer. Patients older than 60 years who are receiving heart transplants had the highest 5-year cumulative incidence of prostate cancer, at 3.65%. SOTR groups that were found to have 5-year cumulative incidence similar to or greater than the general population at age 50 years (2.34%) were kidney, liver, and lung recipients between 51 and 60 years or older and heart recipients between age 36 to 50 years or older.

Despite this study’s findings, there have also been other studies showing no increased risk or even decreased risk.1 Some of the these disparities may be secondary to PC screening protocols followed prior to transplant including the surgical removal or treatment of PC and/or deferring SOT in patients found to have any evidence of PC.1,2 Therefore, PC screening and diagnosis has become somewhat controversial, especially after transplantation. A group led by Waeckel and colleagues recently reviewed their center’s experience with PC screening in SOTRs and published their findings in International Urology and Nephrology.2

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This was a retrospective study at a single center between 1986 and 2019 evaluating men who were renal transplant recipients (RTRs), hepatic transplant recipients (HTRs) or cardiac transplant recipients (CTRs). All SOTRs older than 50 years underwent a systematic protocol for PC screening with an annual digital rectal exam (DRE) and PSA.  Patients with either an abnormal DRE or PSA < 4 ng/mL underwent ultrasound guided biopsies.

A total of 1565 male patients received a SOT during the 30 year study period: 1000 RTRs, 359 HTRs and 206 CTRs. The incidence of PC in these 3 SOTRs was 3.6%, with an overall mortality of 0.19%.  Most patients were classified as T1 (50.9%). Median age of SOTR was 57.7 years old and PC diagnosis was 64.9 years old. PC diagnosis post SOTR was made predominantly on annual screening (52/57, 91.2%) and rarely based on symptoms. The most common causes for SOTR in each group included: RTR (idiopathic glomerulonephritis and hepatorenal polycystic disease), HTR (alcoholic cirrhosis), and CTR (heart failure secondary to myocardial infarction).  All SOTRs received grafts from brain-dead organ donors; there were no living donors reported. 

There were no statistical differences found when comparing RTR, HTR, and CTR with respect to PC incidence (3.7% vs 4.2% vs 3.4%, P = 0.83) or PC mortality (0.2% vs 0% vs 0.48%, P = 0.32), respectively.  In addition, there were no statistical differences in median age of transplantation (56.8 vs 59 vs 50.8 years, p = 0.26), median age at PC diagnosis (65.7 vs 63.6 vs 63.4 years, p = 0.65), median time between transplantation and PC (78.1 vs 65.4 vs 147.1 months, p = 0.1) and median PSA at PC diagnosis (6.85 vs 6.4 vs 9.4 ng/mL, p = 0.26) between RTR, HTR and CTR, respectively. 

There were no statistical differences between the 3 SOTR groups in Gleason scoring on prostate biopsies and cTNM staging. Radical prostatectomy (RP) was the most common treatment in all 3 groups and included 68.4% of all patients with PC diagnosis.  Global 5 year survival was found to be 79.9%, 85.5% and 41.6% in RTR, HTR and CTR, respectively.

There was an increased standard incidence ratio (SIR) of PC found in all SORs when compared with the national population: 41.9 (OR 43.02; 95% CI, 30.7-60.3], P  < 0.0001). This increased SIR was also found in each individual SOR group: RTR SIR 40.2 (OR, 41.3; 95% CI, 27.7-61.4], P < .0001), HTR SIR 48.4 (OR, 49.6; 95% CI, 28.8-85.4], P < .0001), and CTR SIR 38.9 (OR 40.03; 95% CI, 18.1-85.4], P < 0.0001).

Standardized mortality ratio (SMR) was also increased in the cumulative SORs at 18.75 (OR, 19.2; 95% CI, 5.8-69.8, P <.0001]. Statistically significantly increased SMR was also found in RTR (20, OR 20.04; 95% CI: 4.4-91.6, P =.006) and CTR (SMR 50; OR, 48.8; [95% CI, 6.2-382.8, P = 0.0224] but not HTR (SMR 0, OR 13.2 [95% CI, 0.77-226.4, P = 0.85). 

The authors concluded that based on their protocol, systematic screening of PC in post SOTRs could not be recommended. Consequently, the decision to screen for PC should follow a similar discussion as with the general population. The author’s protocol led to diagnosing many low-risk prostate cancers that increased the SIR but did not lead to decreases in SMR. Therefore this led to an overall “overdiagnosis” of prostate cancer in the SOTR population.

The authors emphasized the decision to screen for PC in SOTRs should be individualized and that utilization of MRI prior to prostate biopsies to eliminate very-low and low-risk prostate cancers from diagnosis should be strongly considered. Active surveillance (AS) is also a reasonable option in these patients as well.

The findings from this study is important to contrast with overall PC statistics that were recently published in the Morbidity and Mortality Weekly Report (MMWR).3 The authors evaluated data from population-based cancer registries within the US and found a total of 3.1 million new cases of PC diagnosed between 2003 and 2017. Age-adjusted incidence decreased from 155 per 100,000 in 2003 to 105 per 100,000 in 2017. Localized, regional, distant, and unknown stage PC was reported as 77%, 11%, 5% and 7%, respectively. Localized cases decreased from 78% in 2003 to 70% in 2017, and distant cases increased from 4% in 2003 to 8% in 2017.

Overall incidence of prostate cancer decreased between 2003 and 2017 (average annual percent change [AAPC]; 2.5%) but increased for cases diagnosed at distant stage (AAPC = 2.2%). Five-year relative survival was 97.6% between 2001 and 2016. 5-year survival for distant prostate cancer improved from 28.7% in 2001-2016 to 32.3% during 2011 to 2016. The 10-year relative survival for local prostate cancer was 100%.

It is important to evaluate these findings in the background of the 2018 US Preventive Services Task Force (USPSTF) recommendations on PC screening, which concluded that the decision to be screened for prostate cancer should be an individual one for men aged 55 to 69 years old,  while men 70 years and older should not be screened for prostate cancer with PSA4. These guidelines reported that PSA-based screening in men between 55 and 69 years old was found to prevent approximately 1.3 deaths from prostate cancer over approximately 13 years per 1000 mean screened. PSA screening may also prevent approximately 3 cases of metastatic PC per 1,000 men screened. This must be weight with potential false positives as well as potential AEs such as erectile dysfunction, urinary incontinence, and fecal urgency.

When comparing the findings from the recent MMWR publication to Waeckel et al, there appears to be a clear difference in 5-yearyear survival. This difference is most likely multifactorial, with a patient’s medical history and immunosuppressive regimen playing key roles. Future studies will need to further clarify if there is any significant difference in immunosuppressive regimens and the risk for PC, and if alterations in this regimen could potentially reduce the risk of PC. Until there are more data, a specific post-SOT PC screening protocol is most likely not required, although real world data may continue to suggest otherwise.

References

  1. Hall EC, Pfeifer RM, Segev DL, Engels EA. Cumulative incidence of cancer after solid organ transplantation. Cancer. 2013;119(12):2300-8. doi:10.1002/cncr.28043. 
  2. Waeckel T, Ait Said K, Altieri M, Belin A, Doefler, Tillou X. Over-diagnosed prostate cancer in solid organ recipients: lessons learned from the last 3 decades. Int Urol Nephrol. 2020. doi:10.1007/s11255-020-02636-2
  3. Siegel DA, O’Neill ME, Richards TB, Dowling NF, Weir HK. Prostate cancer incidence and survival, by stage and race/ethnicity-United States, 2001-2017. MMWR Morb Mortal Wkly Rep. 2020 Oct 16;69(41):1473-1480. doi: 10.15585/mmwr.mm6941a1.
  4. US Preventive Services Task Force, Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, et al. Screening for Prostate Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2018 May 8; 319(18):1901-1913. doi: 10.1001/jama.2018.3710.

This article originally appeared on Cancer Therapy Advisor

Topics:

Prostate Cancer Transplantation