Approximately 20% of patients with renal cell carcinoma (RCC) present with primarily metastatic disease and over 30% of patients with localized RCC will develop distant metastases later, after complete resection of the primary tumor. Accurate postoperative prognostic models are essential for designing personalized surveillance programs, as well as for designing adjuvant therapy and trials. Several clinical and histopathological prognostic factors have been identified and adopted into prognostic algorithms to assess the individual risk for disease recurrence after radical or partial nephrectomy. However, the prediction accuracy of current prognostic models has been studied in retrospective patient cohorts and the optimal set of prognostic features remains unclear. In addition to traditional histopathological prognostic factors, novel biomarkers, such as gene expression profiles and circulating tumor DNA, are extensively studied to supplement existing prognostic algorithms to improve their prediction accuracy. Here, we aim to give an overview of existing prognostic features and prediction models for localized postoperative clear cell RCC and discuss their role in the adjuvant therapy trials. The results of ongoing placebo-controlled adjuvant therapy trials may elucidate prognostic factors and biomarkers that help to define patients at high risk for disease recurrence.

Background: Radium‐233 dichloride is an alpha emitter that specifically targets bone metastases in prostate cancer. Results of a previously reported phase III randomized trial showed survival benefit for radium‐223 compared to best supportive care in castration‐resistant prostate cancer (CRPC) with bone metastases. However, real‐world data are also needed with wider inclusion criteria.Methods: We report results of a retrospective multicenter study including all patients with metastatic CRPC treated with radium‐223 in all five university hospitals in Finland since the introduction of the treatment. We identified 160 patients who had received radium‐223 in Finland in 2014–2019.Results: The median overall survival (OS) was 13.8 months (range 0.5–57 months), and the median real‐world progression‐free survival (rwPFS) was 4.9 months (range 0.5–29.8 months). Alkaline phosphatase (ALP) values within the normal range before and during the radium‐223 treatment or the reduction of elevated ALP to normal range during treatment were associated with better OS when compared to elevated ALP values before and during treatment (p < 0.0001). High prostate‐specific antigen (PSA) level (≥100 μg/L) before radium‐223 treatment was associated with poor OS compared to low PSA level (<20 μg/L) (p = 0.0001). Most patients (57%) experienced pain relief. Pain relief indicated better OS (p = 0.002). Radium‐223 treatment was well tolerated. Toxicity was mostly low grade. Only 12.5% of the patients had grade III–IV adverse events, most commonly anemia, neutropenia, leucopenia, and thrombocytopenia.Conclusion: Radium‐223 was well tolerated in routine clinical practice, and most patients achieved pain relief. Pain relief, ALP normalization, lower baseline PSA, and PSA decrease during radium‐223 treatment were prognostic for better survival. The efficacy of radium‐223 in mCRPC as estimated using OS was comparable to earlier randomized trial in this retrospective real‐world study. Our results support using radium‐223 for mCRPC patients with symptomatic bone metastases even in the era of new‐generation androgen receptor‐targeted agents.

Immune checkpoint inhibitors (ICI) have improved survival in several cancer types. Still, most patients develop disease progression during or after treatment. We evaluated the reasons for treatment discontinuation and their effect on treatment outcomes in adult patients with advanced cancer with ICI in the first or later treatment lines in Southwest Finland between 1 January 2015 and 31 December 2021. Baseline characteristics and treatment outcomes were retrospectively obtained from the electronic medical records. There were 317 patients with 15 different cancer types, most commonly non-small cell lung cancer, melanoma, and kidney cancer, treated with ICI outside clinical trials. During follow-up, 94% of the patients had discontinued treatment. A total of 62% was due to disease progression, 17% due to immune-related adverse events (irAEs), 12% after achieving disease control or radiological response, and 9% due to poor performance status. The median progression-free survival (mPFS) was 5.4 months and the median overall survival (mOS) was 20.3 months in the whole cohort. Longer mPFS and mOS were observed in patients who discontinued ICI due to irAEs (24.3 and 49.2 months) and after disease control (49.7 months and not reached). In total, 46% of the patients who discontinued ICI after irAEs or disease control remained alive and progression-free during follow-up.

After surgery of localized renal cell carcinoma, over 20% of the patients will develop distant metastases. Our aim was to develop an easy-to-use prognostic model for predicting metastasis-free survival after radical or partial nephrectomy of localized clear cell RCC. Model training was performed on 196 patients. Right-censored metastasis-free survival was analysed using LASSO-regularized Cox regression, which identified three key prediction features. The model was validated in an external cohort of 714 patients. 55 (28%) and 134 (19%) patients developed distant metastases during the median postoperative follow-up of 6.3 years (interquartile range 3.4–8.6) and 5.4 years (4.0–7.6) in the training and validation cohort, respectively. Patients were stratified into clinically meaningful risk categories using only three features: tumor size, tumor grade and microvascular invasion, and a representative nomogram and a visual prediction surface were constructed using these features in Cox proportional hazards model. Concordance indices in the training and validation cohorts were 0.755 ± 0.029 and 0.836 ± 0.015 for our novel model, which were comparable to the C-indices of the original Leibovich prediction model (0.734 ± 0.035 and 0.848 ± 0.017, respectively). Thus, the presented model retains high accuracy while requiring only three features that are routinely collected and widely available.

Antibiotic treatment may reduce the efficacy of cancer immunotherapy by disrupting gut microbiome. We aimed to study the association of antibiotics and survival outcomes in advanced cutaneous melanoma and non-small-cell lung cancer (NSCLC) patients who had received anti-PD-1/L1 monotherapy. A total of 222 melanoma and 199 NSCLC patients had received anti-PD-1/L1 monotherapy in 5 Finnish hospitals between January 2014 and December 2020. Clinical characteristics, antibiotic and corticosteroid treatment, and survival outcomes were retrospectively collected from hospital and national medical records. There were 32% of melanoma and 31% of NSCLC patients who had received antibiotic treatment (ABT) 3 months before to 1 month after the first anti-PD-1/L1 antibody infusion. In survival analyses, early antibiotic treatment was associated with inferior overall survival (OS) (ABT 19.2 [17.6-43.7] vs. no ABT 35.6 [29.3-NA] months, P = .033) but not with inferior progression-free survival (PFS) (ABT 5.8 [3.0-12.6] vs. no ABT 10.2 [7.7-15.3] months, P = .3) in melanoma patients and with inferior OS (ABT 8.6 [6.4-12.3] vs. no ABT 18.5 [15.1-21.6] months, P < .001) and PFS (ABT 2.8 [2.1-4.5] vs. no ABT 5.6 [4.4-8.0] months, P = .0081) in NSCLC patients. In multivariable analyses, ABT was not an independent risk-factor for inferior OS and PFS in melanoma but was associated with inferior OS (hazard ratio [HR] 2.12 [1.37-3.28]) and PFS (HR 1.65 [1.10-2.47]) in NSCLC after adjusted for other risk factors. Early ABT was an independent poor risk factor in NSCLC patients who had received anti-PD-1/L1 monotherapy but not in melanoma patients. The weight of ABT as a poor risk factor might depend on other prognostic factors in different cancers.

Melanoma incidence has increased over the last few decades. How the prognosis of a previously diagnosed melanoma may be affected by a woman’s subsequent pregnancy has been debated in the literature since the 1950s, and the outcomes are essential to women who are melanoma survivors in their childbearing years. The main objective of this systematic review is to improve the understanding of whether the course of melanoma in a woman may be altered by a subsequent pregnancy and to help clinicians’ diagnosis. Eligible studies for the systematic review were clinical trials, observational cohort studies and case-control studies that compared prognosis outcomes for non-pregnant patients with melanoma, or pregnant before melanoma diagnosis, versus pregnant patients after a diagnosis of melanoma. The search strategy yielded 1101 articles, of which 4 met the inclusion criteria for the systematic review. All the studies were retrospective non-randomised cohorts with patients with melanomas diagnosed before pregnancy. According to our findings, a subsequent pregnancy was not a significant influence on the outcome of a previous melanoma. However, given the small number of identified studies and the heterogeneous data included, it is recommended to approach these patients with caution, and counselling should be given by known prognostic factors. We also reviewed the medical records of 84 patients of childbearing age (35.8 ± 6.3 years, range 21–45 years) who were diagnosed with cutaneous invasive melanoma in our hospital between 2008 and 2018 (N = 724). Of these, 11 (13.1%) had a pregnancy after melanoma diagnosis (age at pregnancy: 35.6 ± 6.3 years). No statistical differences in outcome were detected.